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CAR T-cell therapy advances in CLL
ORLANDO – Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has demonstrated manageable toxicity and promising clinical activity in the phase 1 portion of a trial enrolling heavily pretreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, according to an investigator.
The overall response rate exceeded 80%, and most patients in response at 6 months had maintained that response at the 9-month mark, said Tanya Siddiqi, MD, of City of Hope National Medical Center, Duarte, Calif.
“Clinical responses were rapid, improved with time, and were deep and durable,” Dr. Siddiqi said at the annual meeting of the American Society of Hematology.
These findings have provided justification for conducting the phase 2 portion of the study, which is currently enrolling at the higher of two dose levels evaluated in phase 1, she added.
Dr. Siddiqi reported on a total of 23 patients enrolled in the study, known as TRANSCEND CLL 004. All patients had relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and had received at least two prior therapies, including ibrutinib, while about one-third had failed venetoclax as well.
The median patient age was 66 years, and 83% had high-risk features, according to Dr. Siddiqi, who said patients had received a median of five prior lines of therapy.
Nine patients were treated at dose level 1, or 50 x 106 CAR+ T cells, while 14 were treated at dose level 2, or 100 x 106 CAR+ T cells. Two patients experienced grade 3 or 4 dose-limiting toxicities at the second level, including hypertension in one patient, and encephalopathy, muscle weakness, and tumor lysis syndrome (TLS) in the other.
Cytokine release syndrome (CRS) occurred in 17 patients, though only two cases reached grade 3. Neurologic adverse events were seen in nine patients, of which five were grade 3 or 4.
Partial or complete responses were noted in 81.5%, or 18 of 22 evaluable patients, including 10 (45.5%) who had complete remission. In the subset of nine patients who had failed both ibrutinib and venetoclax, that overall response rate was a “very impressive” 89% (eight of nine patients), said Dr. Siddiqi, including 67% complete remissions (six patients).
Undetectable minimal residual disease (MRD) was reported in 65% and 75% of patients, depending on the method used to evaluate it.
About two-thirds of the patients had responses by day 30 evaluation, and responses deepened over time in about one-quarter, according to Dr. Siddiqi. Of 12 patients with a response at 6 months, 10 (83%) were still in response at 9 months, and 8 patients have been in response for 12 months or longer, she reported.
Neurologic adverse events seen in the CLL/SLL patients in this study were associated with higher lymph node tumor burden, and increased levels of interleukin(IL)-16 or tumor necrosis factor (TNF), according to further analysis presented by Dr. Siddiqi.
That raises the possibility that IL-16 or TNF may be a “good predictive biomarker” for neurotoxicity, which seems to be driven at least in part by lymphadenopathy. “If there was a way that we could combine the CAR T-cell with something like a novel agent that can shrink the tumor burden quickly, then maybe we can have even less toxicities with these CAR T cells,” Dr. Siddiqi said.
Dr. Siddiqi reported disclosures related to Kite, TG Therapeutics, Celgene, Janssen, Seattle Genetics, AstraZeneca, PCYC, Juno Therapeutics, and BeiGene.
SOURCE: Siddiqi T et al. ASH 2019, Abstract 503.
ORLANDO – Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has demonstrated manageable toxicity and promising clinical activity in the phase 1 portion of a trial enrolling heavily pretreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, according to an investigator.
The overall response rate exceeded 80%, and most patients in response at 6 months had maintained that response at the 9-month mark, said Tanya Siddiqi, MD, of City of Hope National Medical Center, Duarte, Calif.
“Clinical responses were rapid, improved with time, and were deep and durable,” Dr. Siddiqi said at the annual meeting of the American Society of Hematology.
These findings have provided justification for conducting the phase 2 portion of the study, which is currently enrolling at the higher of two dose levels evaluated in phase 1, she added.
Dr. Siddiqi reported on a total of 23 patients enrolled in the study, known as TRANSCEND CLL 004. All patients had relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and had received at least two prior therapies, including ibrutinib, while about one-third had failed venetoclax as well.
The median patient age was 66 years, and 83% had high-risk features, according to Dr. Siddiqi, who said patients had received a median of five prior lines of therapy.
Nine patients were treated at dose level 1, or 50 x 106 CAR+ T cells, while 14 were treated at dose level 2, or 100 x 106 CAR+ T cells. Two patients experienced grade 3 or 4 dose-limiting toxicities at the second level, including hypertension in one patient, and encephalopathy, muscle weakness, and tumor lysis syndrome (TLS) in the other.
Cytokine release syndrome (CRS) occurred in 17 patients, though only two cases reached grade 3. Neurologic adverse events were seen in nine patients, of which five were grade 3 or 4.
Partial or complete responses were noted in 81.5%, or 18 of 22 evaluable patients, including 10 (45.5%) who had complete remission. In the subset of nine patients who had failed both ibrutinib and venetoclax, that overall response rate was a “very impressive” 89% (eight of nine patients), said Dr. Siddiqi, including 67% complete remissions (six patients).
Undetectable minimal residual disease (MRD) was reported in 65% and 75% of patients, depending on the method used to evaluate it.
About two-thirds of the patients had responses by day 30 evaluation, and responses deepened over time in about one-quarter, according to Dr. Siddiqi. Of 12 patients with a response at 6 months, 10 (83%) were still in response at 9 months, and 8 patients have been in response for 12 months or longer, she reported.
Neurologic adverse events seen in the CLL/SLL patients in this study were associated with higher lymph node tumor burden, and increased levels of interleukin(IL)-16 or tumor necrosis factor (TNF), according to further analysis presented by Dr. Siddiqi.
That raises the possibility that IL-16 or TNF may be a “good predictive biomarker” for neurotoxicity, which seems to be driven at least in part by lymphadenopathy. “If there was a way that we could combine the CAR T-cell with something like a novel agent that can shrink the tumor burden quickly, then maybe we can have even less toxicities with these CAR T cells,” Dr. Siddiqi said.
Dr. Siddiqi reported disclosures related to Kite, TG Therapeutics, Celgene, Janssen, Seattle Genetics, AstraZeneca, PCYC, Juno Therapeutics, and BeiGene.
SOURCE: Siddiqi T et al. ASH 2019, Abstract 503.
ORLANDO – Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has demonstrated manageable toxicity and promising clinical activity in the phase 1 portion of a trial enrolling heavily pretreated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, according to an investigator.
The overall response rate exceeded 80%, and most patients in response at 6 months had maintained that response at the 9-month mark, said Tanya Siddiqi, MD, of City of Hope National Medical Center, Duarte, Calif.
“Clinical responses were rapid, improved with time, and were deep and durable,” Dr. Siddiqi said at the annual meeting of the American Society of Hematology.
These findings have provided justification for conducting the phase 2 portion of the study, which is currently enrolling at the higher of two dose levels evaluated in phase 1, she added.
Dr. Siddiqi reported on a total of 23 patients enrolled in the study, known as TRANSCEND CLL 004. All patients had relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and had received at least two prior therapies, including ibrutinib, while about one-third had failed venetoclax as well.
The median patient age was 66 years, and 83% had high-risk features, according to Dr. Siddiqi, who said patients had received a median of five prior lines of therapy.
Nine patients were treated at dose level 1, or 50 x 106 CAR+ T cells, while 14 were treated at dose level 2, or 100 x 106 CAR+ T cells. Two patients experienced grade 3 or 4 dose-limiting toxicities at the second level, including hypertension in one patient, and encephalopathy, muscle weakness, and tumor lysis syndrome (TLS) in the other.
Cytokine release syndrome (CRS) occurred in 17 patients, though only two cases reached grade 3. Neurologic adverse events were seen in nine patients, of which five were grade 3 or 4.
Partial or complete responses were noted in 81.5%, or 18 of 22 evaluable patients, including 10 (45.5%) who had complete remission. In the subset of nine patients who had failed both ibrutinib and venetoclax, that overall response rate was a “very impressive” 89% (eight of nine patients), said Dr. Siddiqi, including 67% complete remissions (six patients).
Undetectable minimal residual disease (MRD) was reported in 65% and 75% of patients, depending on the method used to evaluate it.
About two-thirds of the patients had responses by day 30 evaluation, and responses deepened over time in about one-quarter, according to Dr. Siddiqi. Of 12 patients with a response at 6 months, 10 (83%) were still in response at 9 months, and 8 patients have been in response for 12 months or longer, she reported.
Neurologic adverse events seen in the CLL/SLL patients in this study were associated with higher lymph node tumor burden, and increased levels of interleukin(IL)-16 or tumor necrosis factor (TNF), according to further analysis presented by Dr. Siddiqi.
That raises the possibility that IL-16 or TNF may be a “good predictive biomarker” for neurotoxicity, which seems to be driven at least in part by lymphadenopathy. “If there was a way that we could combine the CAR T-cell with something like a novel agent that can shrink the tumor burden quickly, then maybe we can have even less toxicities with these CAR T cells,” Dr. Siddiqi said.
Dr. Siddiqi reported disclosures related to Kite, TG Therapeutics, Celgene, Janssen, Seattle Genetics, AstraZeneca, PCYC, Juno Therapeutics, and BeiGene.
SOURCE: Siddiqi T et al. ASH 2019, Abstract 503.
REPORTING FROM ASH 2019
Inhibitor appears to strengthen anti-BCMA CAR T cells in myeloma patients
ORLANDO – A gamma secretase inhibitor could enhance the efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory multiple myeloma, a phase 1 trial suggests.
The inhibitor, JSMD194, increased BCMA expression in all 10 patients studied. All patients responded to anti-BCMA CAR T-cell therapy, including three patients who had previously failed BCMA-directed therapy.
Nine patients remain alive and in response at a median follow-up of 20 weeks, with two patients being followed for more than a year. One patient experienced dose-limiting toxicity and died, which prompted a change to the study’s eligibility criteria.
Andrew J. Cowan, MD, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, presented these results at the annual meeting of the American Society of Hematology.
Dr. Cowan and colleagues previously showed that treatment with a gamma secretase inhibitor increased BCMA expression on tumor cells and improved the efficacy of BCMA-targeted CAR T cells in a mouse model of multiple myeloma. The team also showed that a gamma secretase inhibitor could “markedly” increase the percentage of BCMA-positive tumor cells in myeloma patients (Blood. 2019 Nov 7;134[19]:1585-97).
To expand upon these findings, the researchers began a phase 1 trial of BCMA-directed CAR T cells and the oral gamma secretase inhibitor JSMD194 in patients with relapsed/refractory multiple myeloma.
Ten patients have been treated, five men and five women. The patients’ median age at baseline was 66 years (range, 44-74 years). They received a median of 10 prior therapies (range, 4-23). Nine patients had received at least one autologous stem cell transplant, and one patient had two. One patient underwent allogeneic transplant (as well as autologous transplant).
Three patients had received prior BCMA-directed therapy. Two patients had received BCMA-directed CAR T cells. One of them did not respond, and the other responded but relapsed. The third patient received a BCMA-targeted bispecific T-cell engager and did not respond.
Study treatment
Patients had BCMA expression measured at baseline, then underwent apheresis for CAR T-cell production.
Patients received JSMD194 at 25 mg on days 1, 3, and 5. Then, they received cyclophosphamide at 300 mg and fludarabine at 25 mg for 3 days.
Next, patients received a single CAR T-cell infusion at a dose of 50 x 106 (n = 5), 150 x 106 (n = 3), or 300 x 106 (n = 2). They also received JSMD194 at 25 mg three times a week for 3 weeks.
Safety
“Nearly all patients had a serious adverse event, which was typically admission to the hospital for neutropenic fever,” Dr. Cowan said.
One patient experienced dose-limiting toxicity and died at day 33. The patient had a disseminating fungal infection, grade 4 cytokine release syndrome (CRS), and neurotoxicity. The patient’s death prompted the researchers to include performance status in the study’s eligibility criteria.
All patients developed CRS. Only the aforementioned patient had grade 4 CRS, and three patients had grade 3 CRS. Six patients experienced neurotoxicity. There were no cases of tumor lysis syndrome.
Efficacy
“All patients experienced an increase of cells expressing BCMA,” Dr. Cowan said. “While there was significant variability in BCMA expression at baseline, all cells expressed BCMA after three doses of the gamma secretase inhibitor.”
The median BCMA expression after JSMD194 treatment was 99% (range, 96%-100%), and there was a median 20-fold (range, 8- to 157-fold) increase in BCMA surface density.
The overall response rate was 100%. Two patients achieved a stringent complete response (CR), one achieved a CR, five patients had a very good partial response, and two had a partial response.
The patient with a CR received the 50 x 106 dose of CAR T cells, and the patients with stringent CRs received the 150 x 106 and 300 x 106 doses.
Of the three patients who previously received BCMA-directed therapy, two achieved a very good partial response, and one had a partial response.
Nine of the 10 patients are still alive and in response, with a median follow-up of 20 weeks. The longest follow-up is 444 days.
“To date, all patients have evidence of durable responses,” Dr. Cowan said. “Moreover, all patients had dramatic reductions in involved serum free light chain ... and serum monoclonal proteins.”
Dr. Cowan noted that longer follow-up is needed to assess CAR T-cell persistence and the durability of response.
This trial is sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute. Two researchers involved in this work are employees of Juno Therapeutics. Dr. Cowan reported relationships with Juno Therapeutics, Janssen, Celgene, AbbVie, Cellectar, and Sanofi.
SOURCE: Cowan AJ et al. ASH 2019. Abstract 204.
ORLANDO – A gamma secretase inhibitor could enhance the efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory multiple myeloma, a phase 1 trial suggests.
The inhibitor, JSMD194, increased BCMA expression in all 10 patients studied. All patients responded to anti-BCMA CAR T-cell therapy, including three patients who had previously failed BCMA-directed therapy.
Nine patients remain alive and in response at a median follow-up of 20 weeks, with two patients being followed for more than a year. One patient experienced dose-limiting toxicity and died, which prompted a change to the study’s eligibility criteria.
Andrew J. Cowan, MD, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, presented these results at the annual meeting of the American Society of Hematology.
Dr. Cowan and colleagues previously showed that treatment with a gamma secretase inhibitor increased BCMA expression on tumor cells and improved the efficacy of BCMA-targeted CAR T cells in a mouse model of multiple myeloma. The team also showed that a gamma secretase inhibitor could “markedly” increase the percentage of BCMA-positive tumor cells in myeloma patients (Blood. 2019 Nov 7;134[19]:1585-97).
To expand upon these findings, the researchers began a phase 1 trial of BCMA-directed CAR T cells and the oral gamma secretase inhibitor JSMD194 in patients with relapsed/refractory multiple myeloma.
Ten patients have been treated, five men and five women. The patients’ median age at baseline was 66 years (range, 44-74 years). They received a median of 10 prior therapies (range, 4-23). Nine patients had received at least one autologous stem cell transplant, and one patient had two. One patient underwent allogeneic transplant (as well as autologous transplant).
Three patients had received prior BCMA-directed therapy. Two patients had received BCMA-directed CAR T cells. One of them did not respond, and the other responded but relapsed. The third patient received a BCMA-targeted bispecific T-cell engager and did not respond.
Study treatment
Patients had BCMA expression measured at baseline, then underwent apheresis for CAR T-cell production.
Patients received JSMD194 at 25 mg on days 1, 3, and 5. Then, they received cyclophosphamide at 300 mg and fludarabine at 25 mg for 3 days.
Next, patients received a single CAR T-cell infusion at a dose of 50 x 106 (n = 5), 150 x 106 (n = 3), or 300 x 106 (n = 2). They also received JSMD194 at 25 mg three times a week for 3 weeks.
Safety
“Nearly all patients had a serious adverse event, which was typically admission to the hospital for neutropenic fever,” Dr. Cowan said.
One patient experienced dose-limiting toxicity and died at day 33. The patient had a disseminating fungal infection, grade 4 cytokine release syndrome (CRS), and neurotoxicity. The patient’s death prompted the researchers to include performance status in the study’s eligibility criteria.
All patients developed CRS. Only the aforementioned patient had grade 4 CRS, and three patients had grade 3 CRS. Six patients experienced neurotoxicity. There were no cases of tumor lysis syndrome.
Efficacy
“All patients experienced an increase of cells expressing BCMA,” Dr. Cowan said. “While there was significant variability in BCMA expression at baseline, all cells expressed BCMA after three doses of the gamma secretase inhibitor.”
The median BCMA expression after JSMD194 treatment was 99% (range, 96%-100%), and there was a median 20-fold (range, 8- to 157-fold) increase in BCMA surface density.
The overall response rate was 100%. Two patients achieved a stringent complete response (CR), one achieved a CR, five patients had a very good partial response, and two had a partial response.
The patient with a CR received the 50 x 106 dose of CAR T cells, and the patients with stringent CRs received the 150 x 106 and 300 x 106 doses.
Of the three patients who previously received BCMA-directed therapy, two achieved a very good partial response, and one had a partial response.
Nine of the 10 patients are still alive and in response, with a median follow-up of 20 weeks. The longest follow-up is 444 days.
“To date, all patients have evidence of durable responses,” Dr. Cowan said. “Moreover, all patients had dramatic reductions in involved serum free light chain ... and serum monoclonal proteins.”
Dr. Cowan noted that longer follow-up is needed to assess CAR T-cell persistence and the durability of response.
This trial is sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute. Two researchers involved in this work are employees of Juno Therapeutics. Dr. Cowan reported relationships with Juno Therapeutics, Janssen, Celgene, AbbVie, Cellectar, and Sanofi.
SOURCE: Cowan AJ et al. ASH 2019. Abstract 204.
ORLANDO – A gamma secretase inhibitor could enhance the efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory multiple myeloma, a phase 1 trial suggests.
The inhibitor, JSMD194, increased BCMA expression in all 10 patients studied. All patients responded to anti-BCMA CAR T-cell therapy, including three patients who had previously failed BCMA-directed therapy.
Nine patients remain alive and in response at a median follow-up of 20 weeks, with two patients being followed for more than a year. One patient experienced dose-limiting toxicity and died, which prompted a change to the study’s eligibility criteria.
Andrew J. Cowan, MD, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, presented these results at the annual meeting of the American Society of Hematology.
Dr. Cowan and colleagues previously showed that treatment with a gamma secretase inhibitor increased BCMA expression on tumor cells and improved the efficacy of BCMA-targeted CAR T cells in a mouse model of multiple myeloma. The team also showed that a gamma secretase inhibitor could “markedly” increase the percentage of BCMA-positive tumor cells in myeloma patients (Blood. 2019 Nov 7;134[19]:1585-97).
To expand upon these findings, the researchers began a phase 1 trial of BCMA-directed CAR T cells and the oral gamma secretase inhibitor JSMD194 in patients with relapsed/refractory multiple myeloma.
Ten patients have been treated, five men and five women. The patients’ median age at baseline was 66 years (range, 44-74 years). They received a median of 10 prior therapies (range, 4-23). Nine patients had received at least one autologous stem cell transplant, and one patient had two. One patient underwent allogeneic transplant (as well as autologous transplant).
Three patients had received prior BCMA-directed therapy. Two patients had received BCMA-directed CAR T cells. One of them did not respond, and the other responded but relapsed. The third patient received a BCMA-targeted bispecific T-cell engager and did not respond.
Study treatment
Patients had BCMA expression measured at baseline, then underwent apheresis for CAR T-cell production.
Patients received JSMD194 at 25 mg on days 1, 3, and 5. Then, they received cyclophosphamide at 300 mg and fludarabine at 25 mg for 3 days.
Next, patients received a single CAR T-cell infusion at a dose of 50 x 106 (n = 5), 150 x 106 (n = 3), or 300 x 106 (n = 2). They also received JSMD194 at 25 mg three times a week for 3 weeks.
Safety
“Nearly all patients had a serious adverse event, which was typically admission to the hospital for neutropenic fever,” Dr. Cowan said.
One patient experienced dose-limiting toxicity and died at day 33. The patient had a disseminating fungal infection, grade 4 cytokine release syndrome (CRS), and neurotoxicity. The patient’s death prompted the researchers to include performance status in the study’s eligibility criteria.
All patients developed CRS. Only the aforementioned patient had grade 4 CRS, and three patients had grade 3 CRS. Six patients experienced neurotoxicity. There were no cases of tumor lysis syndrome.
Efficacy
“All patients experienced an increase of cells expressing BCMA,” Dr. Cowan said. “While there was significant variability in BCMA expression at baseline, all cells expressed BCMA after three doses of the gamma secretase inhibitor.”
The median BCMA expression after JSMD194 treatment was 99% (range, 96%-100%), and there was a median 20-fold (range, 8- to 157-fold) increase in BCMA surface density.
The overall response rate was 100%. Two patients achieved a stringent complete response (CR), one achieved a CR, five patients had a very good partial response, and two had a partial response.
The patient with a CR received the 50 x 106 dose of CAR T cells, and the patients with stringent CRs received the 150 x 106 and 300 x 106 doses.
Of the three patients who previously received BCMA-directed therapy, two achieved a very good partial response, and one had a partial response.
Nine of the 10 patients are still alive and in response, with a median follow-up of 20 weeks. The longest follow-up is 444 days.
“To date, all patients have evidence of durable responses,” Dr. Cowan said. “Moreover, all patients had dramatic reductions in involved serum free light chain ... and serum monoclonal proteins.”
Dr. Cowan noted that longer follow-up is needed to assess CAR T-cell persistence and the durability of response.
This trial is sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute. Two researchers involved in this work are employees of Juno Therapeutics. Dr. Cowan reported relationships with Juno Therapeutics, Janssen, Celgene, AbbVie, Cellectar, and Sanofi.
SOURCE: Cowan AJ et al. ASH 2019. Abstract 204.
REPORTING FROM ASH 2019
Survival data reported from largest CAR T trial in B-cell lymphoma
ORLANDO – Updated results from the TRANSCEND NHL trial include survival data with lisocabtagene maraleucel (liso-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory B-cell lymphomas.
The median progression-free survival (PFS) was 6.8 months, and the median overall survival was 21.1 months. PFS results were best among complete responders and among patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma.
Jeremy S. Abramson, MD, of Massachusetts General Hospital in Boston, presented these results at the annual meeting of the American Society of Hematology.
“TRANSCEND NHL is the largest clinical study to date of CD19-directed CAR T cells in patients with relapsed/refractory aggressive B-cell lymphoma,” Dr. Abramson said.
The phase 1 trial (NCT02631044) includes 269 patients who received liso-cel. They were diagnosed with transformed follicular lymphoma (22%) or other indolent lymphoma (7%), high-grade B-cell lymphoma (13%), primary mediastinal large B-cell lymphoma (6%), grade 3B follicular lymphoma (1%), or diffuse large B-cell lymphoma not otherwise specified (51%).
At baseline, patients had received a median of three prior systemic therapies (range, one to eight). Some patients had received autologous (33%) or allogeneic (3%) transplant. Many patients were chemotherapy refractory (67%) or had never achieved a complete response to prior therapy (44%).
More than half of patients (59%) received bridging therapy during liso-cel manufacturing. All patients received lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel at 50 x 106 CAR T cells, 100 x 106 CAR T cells, or 150 x 106 CAR T cells.
Response and survival
The median follow-up was 12.0 months. The overall response rate was 73%, and the complete response rate was 53%.
“Remissions were rapid, with a median of 1 month from CAR T-cell infusion, and durable, with a median duration of response that has not been reached and 55% of patients remaining in response at 1 year,” Dr. Abramson said.
The median PFS was 6.8 months overall, not reached for patients who achieved a complete response, 2.8 months for patients with a partial response, and 1.1 months for patients with stable disease or progressive disease.
The median PFS was not reached for patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma, 5.0 months for high-grade B-cell lymphoma, 3.0 months for diffuse large B-cell lymphoma not otherwise specified, and 2.9 months in transformed indolent non-Hodgkin lymphoma.
The median overall survival was 21.1 months overall, not reached for patients who achieved a complete response, 9.0 months for patients who had a partial response, and 5.1 months for patients with stable disease or progressive disease.
Safety
Common treatment-emergent adverse events were neutropenia (63%), anemia (48%), fatigue (44%), nausea (33%), thrombocytopenia (31%), headache (30%), decreased appetite (28%), and diarrhea (26%).
Cytokine release syndrome (CRS) occurred in 42% of patients, and neurologic events occurred in 30%. Grade 3-4 CRS occurred in 2% of patients, and grade 3-4 neurologic events occurred in 10%. There were no cases of grade 5 CRS or neurologic events.
The median time to CRS onset was 5 days, and the median time to onset of neurologic events was 9 days. The median time to resolution of CRS and neurologic events was 5 days and 11 days, respectively.
“The low incidence of severe CRS and neurologic events and their late time of onset support using this product in a large range of patients and in the outpatient setting,” Dr. Abramson said.
There were seven grade 5 treatment-related adverse events, including diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, cardiomyopathy, fludarabine leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy.
This trial is sponsored by Bristol-Myers Squibb. Dr. Abramson reported relationships with Juno Therapeutics and Celgene, now owned by Bristol-Myers Squibb, and a range of other companies.
SOURCE: Abramson JS et al. ASH 2019, Abstract 241.
ORLANDO – Updated results from the TRANSCEND NHL trial include survival data with lisocabtagene maraleucel (liso-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory B-cell lymphomas.
The median progression-free survival (PFS) was 6.8 months, and the median overall survival was 21.1 months. PFS results were best among complete responders and among patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma.
Jeremy S. Abramson, MD, of Massachusetts General Hospital in Boston, presented these results at the annual meeting of the American Society of Hematology.
“TRANSCEND NHL is the largest clinical study to date of CD19-directed CAR T cells in patients with relapsed/refractory aggressive B-cell lymphoma,” Dr. Abramson said.
The phase 1 trial (NCT02631044) includes 269 patients who received liso-cel. They were diagnosed with transformed follicular lymphoma (22%) or other indolent lymphoma (7%), high-grade B-cell lymphoma (13%), primary mediastinal large B-cell lymphoma (6%), grade 3B follicular lymphoma (1%), or diffuse large B-cell lymphoma not otherwise specified (51%).
At baseline, patients had received a median of three prior systemic therapies (range, one to eight). Some patients had received autologous (33%) or allogeneic (3%) transplant. Many patients were chemotherapy refractory (67%) or had never achieved a complete response to prior therapy (44%).
More than half of patients (59%) received bridging therapy during liso-cel manufacturing. All patients received lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel at 50 x 106 CAR T cells, 100 x 106 CAR T cells, or 150 x 106 CAR T cells.
Response and survival
The median follow-up was 12.0 months. The overall response rate was 73%, and the complete response rate was 53%.
“Remissions were rapid, with a median of 1 month from CAR T-cell infusion, and durable, with a median duration of response that has not been reached and 55% of patients remaining in response at 1 year,” Dr. Abramson said.
The median PFS was 6.8 months overall, not reached for patients who achieved a complete response, 2.8 months for patients with a partial response, and 1.1 months for patients with stable disease or progressive disease.
The median PFS was not reached for patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma, 5.0 months for high-grade B-cell lymphoma, 3.0 months for diffuse large B-cell lymphoma not otherwise specified, and 2.9 months in transformed indolent non-Hodgkin lymphoma.
The median overall survival was 21.1 months overall, not reached for patients who achieved a complete response, 9.0 months for patients who had a partial response, and 5.1 months for patients with stable disease or progressive disease.
Safety
Common treatment-emergent adverse events were neutropenia (63%), anemia (48%), fatigue (44%), nausea (33%), thrombocytopenia (31%), headache (30%), decreased appetite (28%), and diarrhea (26%).
Cytokine release syndrome (CRS) occurred in 42% of patients, and neurologic events occurred in 30%. Grade 3-4 CRS occurred in 2% of patients, and grade 3-4 neurologic events occurred in 10%. There were no cases of grade 5 CRS or neurologic events.
The median time to CRS onset was 5 days, and the median time to onset of neurologic events was 9 days. The median time to resolution of CRS and neurologic events was 5 days and 11 days, respectively.
“The low incidence of severe CRS and neurologic events and their late time of onset support using this product in a large range of patients and in the outpatient setting,” Dr. Abramson said.
There were seven grade 5 treatment-related adverse events, including diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, cardiomyopathy, fludarabine leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy.
This trial is sponsored by Bristol-Myers Squibb. Dr. Abramson reported relationships with Juno Therapeutics and Celgene, now owned by Bristol-Myers Squibb, and a range of other companies.
SOURCE: Abramson JS et al. ASH 2019, Abstract 241.
ORLANDO – Updated results from the TRANSCEND NHL trial include survival data with lisocabtagene maraleucel (liso-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory B-cell lymphomas.
The median progression-free survival (PFS) was 6.8 months, and the median overall survival was 21.1 months. PFS results were best among complete responders and among patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma.
Jeremy S. Abramson, MD, of Massachusetts General Hospital in Boston, presented these results at the annual meeting of the American Society of Hematology.
“TRANSCEND NHL is the largest clinical study to date of CD19-directed CAR T cells in patients with relapsed/refractory aggressive B-cell lymphoma,” Dr. Abramson said.
The phase 1 trial (NCT02631044) includes 269 patients who received liso-cel. They were diagnosed with transformed follicular lymphoma (22%) or other indolent lymphoma (7%), high-grade B-cell lymphoma (13%), primary mediastinal large B-cell lymphoma (6%), grade 3B follicular lymphoma (1%), or diffuse large B-cell lymphoma not otherwise specified (51%).
At baseline, patients had received a median of three prior systemic therapies (range, one to eight). Some patients had received autologous (33%) or allogeneic (3%) transplant. Many patients were chemotherapy refractory (67%) or had never achieved a complete response to prior therapy (44%).
More than half of patients (59%) received bridging therapy during liso-cel manufacturing. All patients received lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel at 50 x 106 CAR T cells, 100 x 106 CAR T cells, or 150 x 106 CAR T cells.
Response and survival
The median follow-up was 12.0 months. The overall response rate was 73%, and the complete response rate was 53%.
“Remissions were rapid, with a median of 1 month from CAR T-cell infusion, and durable, with a median duration of response that has not been reached and 55% of patients remaining in response at 1 year,” Dr. Abramson said.
The median PFS was 6.8 months overall, not reached for patients who achieved a complete response, 2.8 months for patients with a partial response, and 1.1 months for patients with stable disease or progressive disease.
The median PFS was not reached for patients with primary mediastinal large B-cell lymphoma or transformed follicular lymphoma, 5.0 months for high-grade B-cell lymphoma, 3.0 months for diffuse large B-cell lymphoma not otherwise specified, and 2.9 months in transformed indolent non-Hodgkin lymphoma.
The median overall survival was 21.1 months overall, not reached for patients who achieved a complete response, 9.0 months for patients who had a partial response, and 5.1 months for patients with stable disease or progressive disease.
Safety
Common treatment-emergent adverse events were neutropenia (63%), anemia (48%), fatigue (44%), nausea (33%), thrombocytopenia (31%), headache (30%), decreased appetite (28%), and diarrhea (26%).
Cytokine release syndrome (CRS) occurred in 42% of patients, and neurologic events occurred in 30%. Grade 3-4 CRS occurred in 2% of patients, and grade 3-4 neurologic events occurred in 10%. There were no cases of grade 5 CRS or neurologic events.
The median time to CRS onset was 5 days, and the median time to onset of neurologic events was 9 days. The median time to resolution of CRS and neurologic events was 5 days and 11 days, respectively.
“The low incidence of severe CRS and neurologic events and their late time of onset support using this product in a large range of patients and in the outpatient setting,” Dr. Abramson said.
There were seven grade 5 treatment-related adverse events, including diffuse alveolar damage, pulmonary hemorrhage, multiple organ dysfunction syndrome, cardiomyopathy, fludarabine leukoencephalopathy, septic shock, and progressive multifocal leukoencephalopathy.
This trial is sponsored by Bristol-Myers Squibb. Dr. Abramson reported relationships with Juno Therapeutics and Celgene, now owned by Bristol-Myers Squibb, and a range of other companies.
SOURCE: Abramson JS et al. ASH 2019, Abstract 241.
REPORTING FROM ASH 2019
‘Real-world’ data show CAR T therapies are cost effective
ORLANDO – Chimeric antigen receptor (CAR) T-cell therapy has been hailed as a major advance and a game changer, but their cost has redefined the meaning of “expensive.”
However, new “real-world” data now suggests that CAR T-cell therapy may actually be cost effective, as it may lower other expenses related to the illness.
When used in a population of older adults with non-Hodgkin lymphoma, these new data show that CAR T-cell therapy cut related expenditures, compared with health care costs prior to receiving this treatment.
“CAR T therapy was associated with fewer hospitalizations, shorter time in the hospital, fewer ED visits, and lower total health care costs,” said lead study author Karl M. Kilgore, PhD, of Avalere Health in Washington, D.C.
He presented the findings at the 2019 annual meeting of the American Society of Hematology (abstract 793).
CAR T-cell therapies were approved in the United States in 2017. First came tisagenlecleucel (Kymriah, Novartis), for the treatment of pediatric and young adult patients with acute lymphoblastic leukemia, with a price tag of $475,000. Closely following it was axicabtagene ciloleucel (Yescarta, Kite/Gliead), indicated for adult patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who are ineligible for autologous stem cell transplant, with a price tag of $373,000.
The formidable price tags sent shock waves through the blood cancers community, which is struggling to incorporate this novel approach because of the remarkable responses that have been seen.
Real-world experience
In the current study, Dr. Kilgore and colleagues evaluated the demographic and clinical characteristics of Medicare patients who received CAR T therapy (axicabtagene ciloleucel or tisagenlecleucel) and then compared health care utilization, costs, and outcomes pre– and post–CAR T therapy.
“The goal of this study was to look at the real use of CAR T-cell therapy and real-world data on the use of these therapies,” said Dr. Kilgore. “And to look at health care utilization.”
Data was obtained from the Centers for Medicare & Medicaid Services 100% Medicare Fee-for-Service Part A and B claims data, and patients were included in the study if they had been diagnosed with lymphoma and received CAR T therapy between Oct. 1, 2017, and Sept. 30, 2018.
A total of 177 patients met all of the inclusion criteria and were included in the analysis.
The average age was 70 years, more than half (58.8%) were male, and they were primarily white (87.6%). Nearly all patients (91.5%) had a primary diagnosis of diffuse large B-cell lymphoma (DLBCL), as well as multiple comorbidities with 74.6% having a Charlson Comorbidity Index score of 3 or less. Fewer than 5% of patients had undergone a previous autologous stem cell transplant, and 51% had one or more comorbidities that would have disqualified them from participating in CAR T clinical trials (for example, renal failure, heart failure, recent history of deep vein thrombosis/pulmonary embolism).
Just over half of participants (52%) had been treated with intravenous chemotherapy in the 6 months prior to receiving CAR T-cell therapy, and 60% received outpatient lymphodepletion.
During their index episode of care for CAR T infusion, the patients spent a median of 16 days (interquartile range, 10) in the hospital during and 45.5% required ICU care after infusion. In the 6-month period prior to CAR T-cell therapy (preindex), 51.2% had been hospitalized at least once, and almost 20% had three or more periods of hospitalization. Of that group, 27.1% were readmitted during the postindex period.
Among patients who required hospitalization, the median length of stay preindex was 7 days and 5 days post index. The number of ED visits was also lower in the post versus preindex (15.8% vs. 29.9%).
“Patients spent 17% less time in the hospital 6 months after CAR T-cell therapy than before,” he said.
While there were no deaths during the postindex period, a small percentage (less than 5%) were admitted to hospice care. It is unclear if any patients received chemotherapy during the 100-day postindex period, which would suggest disease progression. However, the authors note that claims for the period might be lagging behind for some patients.
Dr. Kilgore pointed out that half of the patients had one or more chronic conditions that, in some cases, would have excluded them from clinical trials. “But 73% remain alive at 6 months,” he said. “We have data that goes out to 21 months, and over 50% are still alive at almost 2 years.”
As for cost, the median total health care costs during the preindex period were $51,999 (mean, 58,820; standard deviation, 45,701) and $14,014 post index (mean, 23,738; SD, 29,698). This extrapolates into $9,749 pre- versus $7,121 post index for each patient per month, which is a 27% decrease in expenditures.
Dr. Kilgore explained that the total paid amounts for CAR T from all sources (Medicare and patient) varied significantly, depending on whether patients were treated in a clinical trial and whether the hospital was reimbursed under standard Medicare prospective payment system for inpatient facilities or through the PPS-exempt payment system.
Impressive survival
Commenting on the study, Sarah Rutherford, MD, a hematologist at Weill Cornell Medical College, New York, and New York–Presbyterian, believes that the key takeaway from this study is that the majority of participants – who were older and sicker than many enrolled on CAR T-cell clinical trials – did quite well.
“Diffuse large B-cell lymphoma is a disease that usually causes people to die quickly if they are refractory to multiple lines of therapy, so the 6-month survival of 75% in this patient population is impressive,” she said. “A large proportion of these patients are likely to have died had they not received CAR T-cell therapy.”
Dr. Rutherford noted that the study authors analyzed the costs associated with patients in the pre– and post–CAR T-cell setting, finding that health care costs were lower following CAR T-cell therapy in this Medicare patient subset, compared with costs prior to the therapy.
“I think CAR T-cell use is certainly justified given the lack of efficacious therapies in relapsed and refractory DLBCL patients, and this study indicates that there may be a financial benefit as well, though the actual costs associated with CAR T-cell therapy were not included in the analysis,” she told Medscape Medical News.
Also weighing in on the study, James Essell, MD, from the U.S. Oncology Network, pointed out that CAR T-cell therapy is changing the paradigm of treatment. For example, refractory lymphoma has a life expectancy of about 6 months. “But with newer data we’re seeing about 50% of patients alive at 3 years after CAR T-cell therapy and we’re thinking that will equate into a cure,” he said.
Dr. Essell explained that, in the past, the scenario would be 6 months of chemotherapy, relapse, other chemotherapy, relapse, and then CAR T, but several clinical trials are now looking at giving CAR T at first relapse. “Instead of waiting until they’ve had a transplant, which is going to be about $100,000 at least, they are going to be randomized between autologous transplant and CAR T up front,” he said.
“We are also doing clinical trials through the network for patients who are not candidates for an autologous transplant,” Dr. Essell continued. “They will go straight to CAR-T therapy and that will really increase the cure rate because these are people who weren’t eligible for any curative therapy – and now they are being given a chance.”
Whether CAR T-cell use will expand to broader populations will depend on the results of the randomized trials that are ongoing now, he added.
“That’s our hypotheses right now, but they are being studied in a wide range of hematologic cancers, and in addition, there is a lot of research in solid tumors,” Dr. Essell said. “I don’t think you’d see this mass amount of research and dollars being poured into it if people didn’t think it was going to be a game changer.”
Dr. Kilgore has disclosed research funding from Kite Pharma. Several of the other coauthors have disclosed relationships with industry, which are noted in the abstract. Dr. Essell has disclosed no relevant financial relationships.
A version of this story originally appeared on Medscape.com.
ORLANDO – Chimeric antigen receptor (CAR) T-cell therapy has been hailed as a major advance and a game changer, but their cost has redefined the meaning of “expensive.”
However, new “real-world” data now suggests that CAR T-cell therapy may actually be cost effective, as it may lower other expenses related to the illness.
When used in a population of older adults with non-Hodgkin lymphoma, these new data show that CAR T-cell therapy cut related expenditures, compared with health care costs prior to receiving this treatment.
“CAR T therapy was associated with fewer hospitalizations, shorter time in the hospital, fewer ED visits, and lower total health care costs,” said lead study author Karl M. Kilgore, PhD, of Avalere Health in Washington, D.C.
He presented the findings at the 2019 annual meeting of the American Society of Hematology (abstract 793).
CAR T-cell therapies were approved in the United States in 2017. First came tisagenlecleucel (Kymriah, Novartis), for the treatment of pediatric and young adult patients with acute lymphoblastic leukemia, with a price tag of $475,000. Closely following it was axicabtagene ciloleucel (Yescarta, Kite/Gliead), indicated for adult patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who are ineligible for autologous stem cell transplant, with a price tag of $373,000.
The formidable price tags sent shock waves through the blood cancers community, which is struggling to incorporate this novel approach because of the remarkable responses that have been seen.
Real-world experience
In the current study, Dr. Kilgore and colleagues evaluated the demographic and clinical characteristics of Medicare patients who received CAR T therapy (axicabtagene ciloleucel or tisagenlecleucel) and then compared health care utilization, costs, and outcomes pre– and post–CAR T therapy.
“The goal of this study was to look at the real use of CAR T-cell therapy and real-world data on the use of these therapies,” said Dr. Kilgore. “And to look at health care utilization.”
Data was obtained from the Centers for Medicare & Medicaid Services 100% Medicare Fee-for-Service Part A and B claims data, and patients were included in the study if they had been diagnosed with lymphoma and received CAR T therapy between Oct. 1, 2017, and Sept. 30, 2018.
A total of 177 patients met all of the inclusion criteria and were included in the analysis.
The average age was 70 years, more than half (58.8%) were male, and they were primarily white (87.6%). Nearly all patients (91.5%) had a primary diagnosis of diffuse large B-cell lymphoma (DLBCL), as well as multiple comorbidities with 74.6% having a Charlson Comorbidity Index score of 3 or less. Fewer than 5% of patients had undergone a previous autologous stem cell transplant, and 51% had one or more comorbidities that would have disqualified them from participating in CAR T clinical trials (for example, renal failure, heart failure, recent history of deep vein thrombosis/pulmonary embolism).
Just over half of participants (52%) had been treated with intravenous chemotherapy in the 6 months prior to receiving CAR T-cell therapy, and 60% received outpatient lymphodepletion.
During their index episode of care for CAR T infusion, the patients spent a median of 16 days (interquartile range, 10) in the hospital during and 45.5% required ICU care after infusion. In the 6-month period prior to CAR T-cell therapy (preindex), 51.2% had been hospitalized at least once, and almost 20% had three or more periods of hospitalization. Of that group, 27.1% were readmitted during the postindex period.
Among patients who required hospitalization, the median length of stay preindex was 7 days and 5 days post index. The number of ED visits was also lower in the post versus preindex (15.8% vs. 29.9%).
“Patients spent 17% less time in the hospital 6 months after CAR T-cell therapy than before,” he said.
While there were no deaths during the postindex period, a small percentage (less than 5%) were admitted to hospice care. It is unclear if any patients received chemotherapy during the 100-day postindex period, which would suggest disease progression. However, the authors note that claims for the period might be lagging behind for some patients.
Dr. Kilgore pointed out that half of the patients had one or more chronic conditions that, in some cases, would have excluded them from clinical trials. “But 73% remain alive at 6 months,” he said. “We have data that goes out to 21 months, and over 50% are still alive at almost 2 years.”
As for cost, the median total health care costs during the preindex period were $51,999 (mean, 58,820; standard deviation, 45,701) and $14,014 post index (mean, 23,738; SD, 29,698). This extrapolates into $9,749 pre- versus $7,121 post index for each patient per month, which is a 27% decrease in expenditures.
Dr. Kilgore explained that the total paid amounts for CAR T from all sources (Medicare and patient) varied significantly, depending on whether patients were treated in a clinical trial and whether the hospital was reimbursed under standard Medicare prospective payment system for inpatient facilities or through the PPS-exempt payment system.
Impressive survival
Commenting on the study, Sarah Rutherford, MD, a hematologist at Weill Cornell Medical College, New York, and New York–Presbyterian, believes that the key takeaway from this study is that the majority of participants – who were older and sicker than many enrolled on CAR T-cell clinical trials – did quite well.
“Diffuse large B-cell lymphoma is a disease that usually causes people to die quickly if they are refractory to multiple lines of therapy, so the 6-month survival of 75% in this patient population is impressive,” she said. “A large proportion of these patients are likely to have died had they not received CAR T-cell therapy.”
Dr. Rutherford noted that the study authors analyzed the costs associated with patients in the pre– and post–CAR T-cell setting, finding that health care costs were lower following CAR T-cell therapy in this Medicare patient subset, compared with costs prior to the therapy.
“I think CAR T-cell use is certainly justified given the lack of efficacious therapies in relapsed and refractory DLBCL patients, and this study indicates that there may be a financial benefit as well, though the actual costs associated with CAR T-cell therapy were not included in the analysis,” she told Medscape Medical News.
Also weighing in on the study, James Essell, MD, from the U.S. Oncology Network, pointed out that CAR T-cell therapy is changing the paradigm of treatment. For example, refractory lymphoma has a life expectancy of about 6 months. “But with newer data we’re seeing about 50% of patients alive at 3 years after CAR T-cell therapy and we’re thinking that will equate into a cure,” he said.
Dr. Essell explained that, in the past, the scenario would be 6 months of chemotherapy, relapse, other chemotherapy, relapse, and then CAR T, but several clinical trials are now looking at giving CAR T at first relapse. “Instead of waiting until they’ve had a transplant, which is going to be about $100,000 at least, they are going to be randomized between autologous transplant and CAR T up front,” he said.
“We are also doing clinical trials through the network for patients who are not candidates for an autologous transplant,” Dr. Essell continued. “They will go straight to CAR-T therapy and that will really increase the cure rate because these are people who weren’t eligible for any curative therapy – and now they are being given a chance.”
Whether CAR T-cell use will expand to broader populations will depend on the results of the randomized trials that are ongoing now, he added.
“That’s our hypotheses right now, but they are being studied in a wide range of hematologic cancers, and in addition, there is a lot of research in solid tumors,” Dr. Essell said. “I don’t think you’d see this mass amount of research and dollars being poured into it if people didn’t think it was going to be a game changer.”
Dr. Kilgore has disclosed research funding from Kite Pharma. Several of the other coauthors have disclosed relationships with industry, which are noted in the abstract. Dr. Essell has disclosed no relevant financial relationships.
A version of this story originally appeared on Medscape.com.
ORLANDO – Chimeric antigen receptor (CAR) T-cell therapy has been hailed as a major advance and a game changer, but their cost has redefined the meaning of “expensive.”
However, new “real-world” data now suggests that CAR T-cell therapy may actually be cost effective, as it may lower other expenses related to the illness.
When used in a population of older adults with non-Hodgkin lymphoma, these new data show that CAR T-cell therapy cut related expenditures, compared with health care costs prior to receiving this treatment.
“CAR T therapy was associated with fewer hospitalizations, shorter time in the hospital, fewer ED visits, and lower total health care costs,” said lead study author Karl M. Kilgore, PhD, of Avalere Health in Washington, D.C.
He presented the findings at the 2019 annual meeting of the American Society of Hematology (abstract 793).
CAR T-cell therapies were approved in the United States in 2017. First came tisagenlecleucel (Kymriah, Novartis), for the treatment of pediatric and young adult patients with acute lymphoblastic leukemia, with a price tag of $475,000. Closely following it was axicabtagene ciloleucel (Yescarta, Kite/Gliead), indicated for adult patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma who are ineligible for autologous stem cell transplant, with a price tag of $373,000.
The formidable price tags sent shock waves through the blood cancers community, which is struggling to incorporate this novel approach because of the remarkable responses that have been seen.
Real-world experience
In the current study, Dr. Kilgore and colleagues evaluated the demographic and clinical characteristics of Medicare patients who received CAR T therapy (axicabtagene ciloleucel or tisagenlecleucel) and then compared health care utilization, costs, and outcomes pre– and post–CAR T therapy.
“The goal of this study was to look at the real use of CAR T-cell therapy and real-world data on the use of these therapies,” said Dr. Kilgore. “And to look at health care utilization.”
Data was obtained from the Centers for Medicare & Medicaid Services 100% Medicare Fee-for-Service Part A and B claims data, and patients were included in the study if they had been diagnosed with lymphoma and received CAR T therapy between Oct. 1, 2017, and Sept. 30, 2018.
A total of 177 patients met all of the inclusion criteria and were included in the analysis.
The average age was 70 years, more than half (58.8%) were male, and they were primarily white (87.6%). Nearly all patients (91.5%) had a primary diagnosis of diffuse large B-cell lymphoma (DLBCL), as well as multiple comorbidities with 74.6% having a Charlson Comorbidity Index score of 3 or less. Fewer than 5% of patients had undergone a previous autologous stem cell transplant, and 51% had one or more comorbidities that would have disqualified them from participating in CAR T clinical trials (for example, renal failure, heart failure, recent history of deep vein thrombosis/pulmonary embolism).
Just over half of participants (52%) had been treated with intravenous chemotherapy in the 6 months prior to receiving CAR T-cell therapy, and 60% received outpatient lymphodepletion.
During their index episode of care for CAR T infusion, the patients spent a median of 16 days (interquartile range, 10) in the hospital during and 45.5% required ICU care after infusion. In the 6-month period prior to CAR T-cell therapy (preindex), 51.2% had been hospitalized at least once, and almost 20% had three or more periods of hospitalization. Of that group, 27.1% were readmitted during the postindex period.
Among patients who required hospitalization, the median length of stay preindex was 7 days and 5 days post index. The number of ED visits was also lower in the post versus preindex (15.8% vs. 29.9%).
“Patients spent 17% less time in the hospital 6 months after CAR T-cell therapy than before,” he said.
While there were no deaths during the postindex period, a small percentage (less than 5%) were admitted to hospice care. It is unclear if any patients received chemotherapy during the 100-day postindex period, which would suggest disease progression. However, the authors note that claims for the period might be lagging behind for some patients.
Dr. Kilgore pointed out that half of the patients had one or more chronic conditions that, in some cases, would have excluded them from clinical trials. “But 73% remain alive at 6 months,” he said. “We have data that goes out to 21 months, and over 50% are still alive at almost 2 years.”
As for cost, the median total health care costs during the preindex period were $51,999 (mean, 58,820; standard deviation, 45,701) and $14,014 post index (mean, 23,738; SD, 29,698). This extrapolates into $9,749 pre- versus $7,121 post index for each patient per month, which is a 27% decrease in expenditures.
Dr. Kilgore explained that the total paid amounts for CAR T from all sources (Medicare and patient) varied significantly, depending on whether patients were treated in a clinical trial and whether the hospital was reimbursed under standard Medicare prospective payment system for inpatient facilities or through the PPS-exempt payment system.
Impressive survival
Commenting on the study, Sarah Rutherford, MD, a hematologist at Weill Cornell Medical College, New York, and New York–Presbyterian, believes that the key takeaway from this study is that the majority of participants – who were older and sicker than many enrolled on CAR T-cell clinical trials – did quite well.
“Diffuse large B-cell lymphoma is a disease that usually causes people to die quickly if they are refractory to multiple lines of therapy, so the 6-month survival of 75% in this patient population is impressive,” she said. “A large proportion of these patients are likely to have died had they not received CAR T-cell therapy.”
Dr. Rutherford noted that the study authors analyzed the costs associated with patients in the pre– and post–CAR T-cell setting, finding that health care costs were lower following CAR T-cell therapy in this Medicare patient subset, compared with costs prior to the therapy.
“I think CAR T-cell use is certainly justified given the lack of efficacious therapies in relapsed and refractory DLBCL patients, and this study indicates that there may be a financial benefit as well, though the actual costs associated with CAR T-cell therapy were not included in the analysis,” she told Medscape Medical News.
Also weighing in on the study, James Essell, MD, from the U.S. Oncology Network, pointed out that CAR T-cell therapy is changing the paradigm of treatment. For example, refractory lymphoma has a life expectancy of about 6 months. “But with newer data we’re seeing about 50% of patients alive at 3 years after CAR T-cell therapy and we’re thinking that will equate into a cure,” he said.
Dr. Essell explained that, in the past, the scenario would be 6 months of chemotherapy, relapse, other chemotherapy, relapse, and then CAR T, but several clinical trials are now looking at giving CAR T at first relapse. “Instead of waiting until they’ve had a transplant, which is going to be about $100,000 at least, they are going to be randomized between autologous transplant and CAR T up front,” he said.
“We are also doing clinical trials through the network for patients who are not candidates for an autologous transplant,” Dr. Essell continued. “They will go straight to CAR-T therapy and that will really increase the cure rate because these are people who weren’t eligible for any curative therapy – and now they are being given a chance.”
Whether CAR T-cell use will expand to broader populations will depend on the results of the randomized trials that are ongoing now, he added.
“That’s our hypotheses right now, but they are being studied in a wide range of hematologic cancers, and in addition, there is a lot of research in solid tumors,” Dr. Essell said. “I don’t think you’d see this mass amount of research and dollars being poured into it if people didn’t think it was going to be a game changer.”
Dr. Kilgore has disclosed research funding from Kite Pharma. Several of the other coauthors have disclosed relationships with industry, which are noted in the abstract. Dr. Essell has disclosed no relevant financial relationships.
A version of this story originally appeared on Medscape.com.
An off-the-shelf drug to rival CAR T cells: ‘very exciting’
ORLANDO – An investigational drug that can achieve the same results as complex cell therapy is creating a buzz at the American Society of Hematology (ASH) meeting.
For the last few years, attention at this meeting has focused on the chimeric antigen receptor (CAR) T cells, mainly “because of their incredible efficacy,” commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and director of the division of hematology at Johns Hopkins University, Baltimore.
But new results with an off-the-shelf product are “very exciting,” he said, because the drug can be given immediately and appears to achieve similar results.
The new product is mosunetuzumab (Genentech/Roche), a bispecific antibody that targets both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). It works by redirecting T cells to engage and eliminate malignant B cells.
“The concept here is that this monoclonal antibody engages T cells and directs their cytotoxicity against B cells – it’s basically an antibody using the patient’s own T cells to do what a CAR T cell would do,” Dr. Brodsky explained.
However, unlike CAR T cells, which are prepared for each individual patient in a complex process that involves genetic engineering that can take several weeks, mosunetuzumab is an off-the-shelf product that can be given to patients immediately (by intravenous infusion).
This is important, commented Dr. Brodsky, because very-poor-prognosis patients can deteriorate rapidly, and some may not survive while the CAR T cells are being made.
Clinical trial results
Clinical results come from a phase 1/1b trial (known as GO29781) conducted in 270 patients with poor-prognosis refractory/relapsed non-Hodgkin’s lymphoma. These patients had previously been treated with a median of three therapies; in addition, 30 patients (11%) were resistant to or had relapsed after an initial response to CAR T-cell therapy, and 77 patients (29%) had progressed after a stem cell transplant.
“These patients had no available therapy that would be expected to improve survival,” noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.
All patients received mosunetuzumab with an initial treatment of eight cycles. Patients who achieved complete remission (CR) stopped therapy, while patients who had a partial response or had stable disease, continued treatment for 17 cycles.
Two-thirds of patients (n = 180; 67%) had aggressive lymphomas, mainly diffuse large B-cell lymphoma (DLBCL; n = 117), while 85 patients (31%) had indolent disease, mainly follicular lymphoma (FL; n = 82). Objective responses were seen in 46 of 124 patients (37%) with aggressive lymphomas, and 24 (19%) of these patients achieved a CR.
Among patients with indolent lymphoma, objective responses were seen in 42 of 67 patients (63%), and 29 of 67 (43%) had CR.
The complete remissions appear to be long lasting, Dr. Schuster commented. With a median follow-up of 6 months since achieving CR, 17 of 24 patients (71%) with aggressive lymphoma and 24 of 29 patients (83%) with indolent lymphomas remained free of disease.
“Some patients have remained in remission without additional therapy for more than a year,” he commented.
In the subgroup of 30 patients who had previously received CAR T-cell therapy, the objective response rate was 38.9%, and CR was achieved in 4 patients (22%). These rates are similar to what was seen in patients with aggressive lymphoma who had not previously received CAR T-cell therapy, Dr. Schuster commented.
He also noted that in some of these patients, molecular testing showed that the previously administered CAR T cells increased in number. This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR T-cell treatment.
Dr. Schuster also highlighted the results of repeat treatment with mosunetuzumab. Patients who achieved CR stopped treatment – but if they relapsed, they were treated again, and the responses seen on this repeat treatment were similar to those seen with initial treatment. “This is not seen with the CAR T cells,” he noted.
Adverse events with mosunetuzumab were similar to those seen with CAR T cells, he noted, namely cytokine release syndrome, which was mostly mild and seen in 29% of patients, and neurologic toxicity, which was moderately severe in 4% patients.
Overall, the results show that “mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T,” Dr. Schuster commented in a statement.
Approached for comment, Peter Martin MD, chief of the Lymphoma Program at Weill Cornell Medicine, New York, and New York-Presbyterian, said he was excited to see these new data. “It’s good news any time we find something with the potential to save lives.”
“The more options that we have to offer to people with lymphoma the better,” he told Medscape Medical News. “There will always be scenarios where one approach might be better than another. I think there is a good chance that bispecific antibodies will have fairly broad approval in previously treated DLBCL. In many centers, it may be that bispecific antibodies are used most frequently post–CAR T cells, while in other areas people who aren’t candidates for CAR T cells or can’t receive them for whatever reason [could benefit from this new approach].”
Laurie Sehn, MD, MPH, medical oncologist at the University of British Columbia in Vancouver, Canada, and chair of the Lymphoma Tumour Group, as well as an associate editor of ASH journal Blood, also commented for Medscape Medical News.
She agreed that the new data are exciting and noted that this abstract was chosen for the plenary session. She thought the data in the 30 patients who had already been treated with CAR T cells was interesting. “This is a patient population with no other options that offer durable benefit, and mosunetuzumab clearly has clinical activity, with encouraging responses.”
Dr. Sehn also noted that toxicity seen with the drug was “far less” than has been seen with CAR T cells, and the risk of high-grade cytokine release syndrome and neurological toxicity is “very low.”
There are several other new products that are using this bispecific technology, she noted. One example is Regeneron’s REGN1979, a bispecific antibody targeting CD20 and CD3, which is also being investigated in a clinical trial in relapsed/refractory B-cell non-Hodgkin’s lymphoma, including in patients who were previously treated with CAR T cells (abstract 762).
How would it be used clinically?
In response to a question from Medscape Medical News, Dr. Schuster suggested that initial use of mosunetuzumab would be in patients who have already tried CAR T-cell therapy and had either not responded or relapsed – in lymphoma, this is about two-thirds of patients who are treated with this approach. This group of patients represents an unmet medical need, and this indication may be the quickest route to approval, he suggested.
Gary Schiller, MD, from UCLA Health, who moderated the press briefing agreed, and said this would be the quickest route to market because it would need only a phase 2 clinical trial in this specific patient population. But this would likely be only the first use for this product, and then it could be expanded to a broader patient population, he added.
Another use would for mosunetuzumab would be to enhance CAR T-cell responses by redirecting the CAR T cells to other antigens without doing any additional gene editing, Dr. Schuster commented. The idea here is to “revive” previously administered CAR T cells that have stopped working, Dr. Schiller added.
This is a chemotherapy-free approach, Dr. Schuster emphasized. “In patients who have not had a lot of chemotherapy, you can see an increase in T cells,” he commented.
Mosunetuzumab “stimulates and invigorates T cells,” and it could be useful as a pretreatment or a bridge to CAR T-cell therapy, he said.
So the product could be used before CAR T-cell therapy, and equally it could be used after CAR T-cell therapy because it could boost responses in both cases.
“Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents,” he added.
Genentech says that mosunetuzumab and another bispecific antibody, CD20-TCB, are being evaluated in a robust clinical development program, both as a monotherapies and in combination with other therapies, in both aggressive and indolent non-Hodgkin’s lymphoma.
Dr. Schuster reported relationships with Celgene, Genentech, Merck, Pharmacyclics, Acerta, AbbVie, Gilead, Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, and Novartis. Coauthors also have multiple disclosures, and several are employees of Genentech and Roche. Dr. Sehn consults with several pharmaceutics companies, including Verastem, Roche/Genentech, Morphosys, Takeda, Janssen, Lundbeck, Amgen, Teva, and AbbVie.
A version of this story originally appeared on Medscape.com.
ORLANDO – An investigational drug that can achieve the same results as complex cell therapy is creating a buzz at the American Society of Hematology (ASH) meeting.
For the last few years, attention at this meeting has focused on the chimeric antigen receptor (CAR) T cells, mainly “because of their incredible efficacy,” commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and director of the division of hematology at Johns Hopkins University, Baltimore.
But new results with an off-the-shelf product are “very exciting,” he said, because the drug can be given immediately and appears to achieve similar results.
The new product is mosunetuzumab (Genentech/Roche), a bispecific antibody that targets both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). It works by redirecting T cells to engage and eliminate malignant B cells.
“The concept here is that this monoclonal antibody engages T cells and directs their cytotoxicity against B cells – it’s basically an antibody using the patient’s own T cells to do what a CAR T cell would do,” Dr. Brodsky explained.
However, unlike CAR T cells, which are prepared for each individual patient in a complex process that involves genetic engineering that can take several weeks, mosunetuzumab is an off-the-shelf product that can be given to patients immediately (by intravenous infusion).
This is important, commented Dr. Brodsky, because very-poor-prognosis patients can deteriorate rapidly, and some may not survive while the CAR T cells are being made.
Clinical trial results
Clinical results come from a phase 1/1b trial (known as GO29781) conducted in 270 patients with poor-prognosis refractory/relapsed non-Hodgkin’s lymphoma. These patients had previously been treated with a median of three therapies; in addition, 30 patients (11%) were resistant to or had relapsed after an initial response to CAR T-cell therapy, and 77 patients (29%) had progressed after a stem cell transplant.
“These patients had no available therapy that would be expected to improve survival,” noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.
All patients received mosunetuzumab with an initial treatment of eight cycles. Patients who achieved complete remission (CR) stopped therapy, while patients who had a partial response or had stable disease, continued treatment for 17 cycles.
Two-thirds of patients (n = 180; 67%) had aggressive lymphomas, mainly diffuse large B-cell lymphoma (DLBCL; n = 117), while 85 patients (31%) had indolent disease, mainly follicular lymphoma (FL; n = 82). Objective responses were seen in 46 of 124 patients (37%) with aggressive lymphomas, and 24 (19%) of these patients achieved a CR.
Among patients with indolent lymphoma, objective responses were seen in 42 of 67 patients (63%), and 29 of 67 (43%) had CR.
The complete remissions appear to be long lasting, Dr. Schuster commented. With a median follow-up of 6 months since achieving CR, 17 of 24 patients (71%) with aggressive lymphoma and 24 of 29 patients (83%) with indolent lymphomas remained free of disease.
“Some patients have remained in remission without additional therapy for more than a year,” he commented.
In the subgroup of 30 patients who had previously received CAR T-cell therapy, the objective response rate was 38.9%, and CR was achieved in 4 patients (22%). These rates are similar to what was seen in patients with aggressive lymphoma who had not previously received CAR T-cell therapy, Dr. Schuster commented.
He also noted that in some of these patients, molecular testing showed that the previously administered CAR T cells increased in number. This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR T-cell treatment.
Dr. Schuster also highlighted the results of repeat treatment with mosunetuzumab. Patients who achieved CR stopped treatment – but if they relapsed, they were treated again, and the responses seen on this repeat treatment were similar to those seen with initial treatment. “This is not seen with the CAR T cells,” he noted.
Adverse events with mosunetuzumab were similar to those seen with CAR T cells, he noted, namely cytokine release syndrome, which was mostly mild and seen in 29% of patients, and neurologic toxicity, which was moderately severe in 4% patients.
Overall, the results show that “mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T,” Dr. Schuster commented in a statement.
Approached for comment, Peter Martin MD, chief of the Lymphoma Program at Weill Cornell Medicine, New York, and New York-Presbyterian, said he was excited to see these new data. “It’s good news any time we find something with the potential to save lives.”
“The more options that we have to offer to people with lymphoma the better,” he told Medscape Medical News. “There will always be scenarios where one approach might be better than another. I think there is a good chance that bispecific antibodies will have fairly broad approval in previously treated DLBCL. In many centers, it may be that bispecific antibodies are used most frequently post–CAR T cells, while in other areas people who aren’t candidates for CAR T cells or can’t receive them for whatever reason [could benefit from this new approach].”
Laurie Sehn, MD, MPH, medical oncologist at the University of British Columbia in Vancouver, Canada, and chair of the Lymphoma Tumour Group, as well as an associate editor of ASH journal Blood, also commented for Medscape Medical News.
She agreed that the new data are exciting and noted that this abstract was chosen for the plenary session. She thought the data in the 30 patients who had already been treated with CAR T cells was interesting. “This is a patient population with no other options that offer durable benefit, and mosunetuzumab clearly has clinical activity, with encouraging responses.”
Dr. Sehn also noted that toxicity seen with the drug was “far less” than has been seen with CAR T cells, and the risk of high-grade cytokine release syndrome and neurological toxicity is “very low.”
There are several other new products that are using this bispecific technology, she noted. One example is Regeneron’s REGN1979, a bispecific antibody targeting CD20 and CD3, which is also being investigated in a clinical trial in relapsed/refractory B-cell non-Hodgkin’s lymphoma, including in patients who were previously treated with CAR T cells (abstract 762).
How would it be used clinically?
In response to a question from Medscape Medical News, Dr. Schuster suggested that initial use of mosunetuzumab would be in patients who have already tried CAR T-cell therapy and had either not responded or relapsed – in lymphoma, this is about two-thirds of patients who are treated with this approach. This group of patients represents an unmet medical need, and this indication may be the quickest route to approval, he suggested.
Gary Schiller, MD, from UCLA Health, who moderated the press briefing agreed, and said this would be the quickest route to market because it would need only a phase 2 clinical trial in this specific patient population. But this would likely be only the first use for this product, and then it could be expanded to a broader patient population, he added.
Another use would for mosunetuzumab would be to enhance CAR T-cell responses by redirecting the CAR T cells to other antigens without doing any additional gene editing, Dr. Schuster commented. The idea here is to “revive” previously administered CAR T cells that have stopped working, Dr. Schiller added.
This is a chemotherapy-free approach, Dr. Schuster emphasized. “In patients who have not had a lot of chemotherapy, you can see an increase in T cells,” he commented.
Mosunetuzumab “stimulates and invigorates T cells,” and it could be useful as a pretreatment or a bridge to CAR T-cell therapy, he said.
So the product could be used before CAR T-cell therapy, and equally it could be used after CAR T-cell therapy because it could boost responses in both cases.
“Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents,” he added.
Genentech says that mosunetuzumab and another bispecific antibody, CD20-TCB, are being evaluated in a robust clinical development program, both as a monotherapies and in combination with other therapies, in both aggressive and indolent non-Hodgkin’s lymphoma.
Dr. Schuster reported relationships with Celgene, Genentech, Merck, Pharmacyclics, Acerta, AbbVie, Gilead, Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, and Novartis. Coauthors also have multiple disclosures, and several are employees of Genentech and Roche. Dr. Sehn consults with several pharmaceutics companies, including Verastem, Roche/Genentech, Morphosys, Takeda, Janssen, Lundbeck, Amgen, Teva, and AbbVie.
A version of this story originally appeared on Medscape.com.
ORLANDO – An investigational drug that can achieve the same results as complex cell therapy is creating a buzz at the American Society of Hematology (ASH) meeting.
For the last few years, attention at this meeting has focused on the chimeric antigen receptor (CAR) T cells, mainly “because of their incredible efficacy,” commented ASH Secretary Robert A. Brodsky, MD, professor of medicine and director of the division of hematology at Johns Hopkins University, Baltimore.
But new results with an off-the-shelf product are “very exciting,” he said, because the drug can be given immediately and appears to achieve similar results.
The new product is mosunetuzumab (Genentech/Roche), a bispecific antibody that targets both CD3 (on the surface of T cells) and CD20 (on the surface of B cells). It works by redirecting T cells to engage and eliminate malignant B cells.
“The concept here is that this monoclonal antibody engages T cells and directs their cytotoxicity against B cells – it’s basically an antibody using the patient’s own T cells to do what a CAR T cell would do,” Dr. Brodsky explained.
However, unlike CAR T cells, which are prepared for each individual patient in a complex process that involves genetic engineering that can take several weeks, mosunetuzumab is an off-the-shelf product that can be given to patients immediately (by intravenous infusion).
This is important, commented Dr. Brodsky, because very-poor-prognosis patients can deteriorate rapidly, and some may not survive while the CAR T cells are being made.
Clinical trial results
Clinical results come from a phase 1/1b trial (known as GO29781) conducted in 270 patients with poor-prognosis refractory/relapsed non-Hodgkin’s lymphoma. These patients had previously been treated with a median of three therapies; in addition, 30 patients (11%) were resistant to or had relapsed after an initial response to CAR T-cell therapy, and 77 patients (29%) had progressed after a stem cell transplant.
“These patients had no available therapy that would be expected to improve survival,” noted lead author Stephen J. Schuster, MD, of Abramson Cancer Center at the University of Pennsylvania in Philadelphia.
All patients received mosunetuzumab with an initial treatment of eight cycles. Patients who achieved complete remission (CR) stopped therapy, while patients who had a partial response or had stable disease, continued treatment for 17 cycles.
Two-thirds of patients (n = 180; 67%) had aggressive lymphomas, mainly diffuse large B-cell lymphoma (DLBCL; n = 117), while 85 patients (31%) had indolent disease, mainly follicular lymphoma (FL; n = 82). Objective responses were seen in 46 of 124 patients (37%) with aggressive lymphomas, and 24 (19%) of these patients achieved a CR.
Among patients with indolent lymphoma, objective responses were seen in 42 of 67 patients (63%), and 29 of 67 (43%) had CR.
The complete remissions appear to be long lasting, Dr. Schuster commented. With a median follow-up of 6 months since achieving CR, 17 of 24 patients (71%) with aggressive lymphoma and 24 of 29 patients (83%) with indolent lymphomas remained free of disease.
“Some patients have remained in remission without additional therapy for more than a year,” he commented.
In the subgroup of 30 patients who had previously received CAR T-cell therapy, the objective response rate was 38.9%, and CR was achieved in 4 patients (22%). These rates are similar to what was seen in patients with aggressive lymphoma who had not previously received CAR T-cell therapy, Dr. Schuster commented.
He also noted that in some of these patients, molecular testing showed that the previously administered CAR T cells increased in number. This suggests that, in addition to its ability to kill cancerous B cells, mosunetuzumab may also help augment the effect of the prior CAR T-cell treatment.
Dr. Schuster also highlighted the results of repeat treatment with mosunetuzumab. Patients who achieved CR stopped treatment – but if they relapsed, they were treated again, and the responses seen on this repeat treatment were similar to those seen with initial treatment. “This is not seen with the CAR T cells,” he noted.
Adverse events with mosunetuzumab were similar to those seen with CAR T cells, he noted, namely cytokine release syndrome, which was mostly mild and seen in 29% of patients, and neurologic toxicity, which was moderately severe in 4% patients.
Overall, the results show that “mosunetuzumab generates long-lasting responses with a very tolerable safety profile in patients with B-cell non-Hodgkin lymphomas for whom multiple prior treatments have failed and whose prognosis is poor. Of particular interest, we are seeing durable complete remissions in patients whose lymphomas progressed after CAR T,” Dr. Schuster commented in a statement.
Approached for comment, Peter Martin MD, chief of the Lymphoma Program at Weill Cornell Medicine, New York, and New York-Presbyterian, said he was excited to see these new data. “It’s good news any time we find something with the potential to save lives.”
“The more options that we have to offer to people with lymphoma the better,” he told Medscape Medical News. “There will always be scenarios where one approach might be better than another. I think there is a good chance that bispecific antibodies will have fairly broad approval in previously treated DLBCL. In many centers, it may be that bispecific antibodies are used most frequently post–CAR T cells, while in other areas people who aren’t candidates for CAR T cells or can’t receive them for whatever reason [could benefit from this new approach].”
Laurie Sehn, MD, MPH, medical oncologist at the University of British Columbia in Vancouver, Canada, and chair of the Lymphoma Tumour Group, as well as an associate editor of ASH journal Blood, also commented for Medscape Medical News.
She agreed that the new data are exciting and noted that this abstract was chosen for the plenary session. She thought the data in the 30 patients who had already been treated with CAR T cells was interesting. “This is a patient population with no other options that offer durable benefit, and mosunetuzumab clearly has clinical activity, with encouraging responses.”
Dr. Sehn also noted that toxicity seen with the drug was “far less” than has been seen with CAR T cells, and the risk of high-grade cytokine release syndrome and neurological toxicity is “very low.”
There are several other new products that are using this bispecific technology, she noted. One example is Regeneron’s REGN1979, a bispecific antibody targeting CD20 and CD3, which is also being investigated in a clinical trial in relapsed/refractory B-cell non-Hodgkin’s lymphoma, including in patients who were previously treated with CAR T cells (abstract 762).
How would it be used clinically?
In response to a question from Medscape Medical News, Dr. Schuster suggested that initial use of mosunetuzumab would be in patients who have already tried CAR T-cell therapy and had either not responded or relapsed – in lymphoma, this is about two-thirds of patients who are treated with this approach. This group of patients represents an unmet medical need, and this indication may be the quickest route to approval, he suggested.
Gary Schiller, MD, from UCLA Health, who moderated the press briefing agreed, and said this would be the quickest route to market because it would need only a phase 2 clinical trial in this specific patient population. But this would likely be only the first use for this product, and then it could be expanded to a broader patient population, he added.
Another use would for mosunetuzumab would be to enhance CAR T-cell responses by redirecting the CAR T cells to other antigens without doing any additional gene editing, Dr. Schuster commented. The idea here is to “revive” previously administered CAR T cells that have stopped working, Dr. Schiller added.
This is a chemotherapy-free approach, Dr. Schuster emphasized. “In patients who have not had a lot of chemotherapy, you can see an increase in T cells,” he commented.
Mosunetuzumab “stimulates and invigorates T cells,” and it could be useful as a pretreatment or a bridge to CAR T-cell therapy, he said.
So the product could be used before CAR T-cell therapy, and equally it could be used after CAR T-cell therapy because it could boost responses in both cases.
“Larger, randomized trials are needed to further confirm these promising data and determine whether the treatment benefit of mosunetuzumab is enhanced when it is used earlier in the course of lymphoma therapy or in combination with other agents,” he added.
Genentech says that mosunetuzumab and another bispecific antibody, CD20-TCB, are being evaluated in a robust clinical development program, both as a monotherapies and in combination with other therapies, in both aggressive and indolent non-Hodgkin’s lymphoma.
Dr. Schuster reported relationships with Celgene, Genentech, Merck, Pharmacyclics, Acerta, AbbVie, Gilead, Nordic Nanovector, Pfizer, AstraZeneca, Loxo Oncology, and Novartis. Coauthors also have multiple disclosures, and several are employees of Genentech and Roche. Dr. Sehn consults with several pharmaceutics companies, including Verastem, Roche/Genentech, Morphosys, Takeda, Janssen, Lundbeck, Amgen, Teva, and AbbVie.
A version of this story originally appeared on Medscape.com.
Pembrolizumab plus chemo boosts pCR rate in TNBC
SAN ANTONIO – Adding pembrolizumab to chemotherapy in the neoadjuvant setting increased the likelihood that women with stage III or early node-positive triple-negative breast cancer (TNBC) would have a pathologic complete response and sustained clinical benefit, results of the phase 3 KEYNOTE-522 study showed.
Among 602 patients evaluable in a definitive pathological complete response (pCR) analysis, the pCR rate was 64.8% for those treated with chemotherapy plus pembrolizumab (Keytruda), compared with 51.2% for patients treated with chemotherapy plus placebo, reported Peter Schmid, MD, PhD, from Barts Cancer Institute in London.
“The addition of neoadjuvant pembrolizumab to chemotherapy provided a significant increase in the path CR rate in all patients, but also a larger magnitude of path CR benefit versus chemotherapy alone in patients with higher-risk disease, such as stage III disease or node-positive early triple-negative breast cancer,” he said at the annual San Antonio Breast Cancer Symposium.
The overall pCR results were originally reported at the 2019 annual meeting of the European Society for Medical Oncology. At SABCS 2019, he reported pCR results for specific subgroups in KEYNOTE-522.
Investigators enrolled patients aged 18 years or older with newly diagnosed TNBC of either stage T1cN1-2, or T2-4N0-2 and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients also had to have at least two separate tumor cores from the primary tumor for assessment of programmed death–ligand 1 (PD-L1).
After stratification for nodal status, tumor size, and carboplatin schedule (once weekly or every 3 weeks), patients were randomized to receive either pembrolizumab 200 mg every 3 weeks or placebo plus neoadjuvant carboplatin and paclitaxel for four 3-week cycles, followed by four cycles of chemotherapy with either doxorubicin or epirubicin plus cyclophosphamide (AC or EC). Patients went on to surgery, then received adjuvant therapy for nine cycles with either pembrolizumab at the neoadjuvant dose and schedule or placebo.
At the first preplanned interim analysis for event-free survival (EFS) based on 1,174 patients followed for a median of 15.5 months, events had occurred in 7.4% of patients on pembro/chemo, compared with 11.8% on placebo/chemo, but this difference did not meet the prespecified P value boundary of .000051 for significance, Dr. Schmid acknowledged.
When the investigators looked at pCR by disease stage, however, they saw the following benefits across all stages in the study:
- Stage IIA: 73.1% with pembrolizumab versus 62.1% with placebo, difference 11%.
- Stage IIB: 56.2% versus 48.4%, difference 7.8%.
- Stage IIIA: 66.7% versus 42.1%, difference 24.6%.
- Stage IIIB: 48.6% versus 23.1%, difference 25.6%.
The greatest benefit for the addition of pembrolizumab to chemotherapy appeared to be in the higher disease stages, Dr. Schmid said.
There was also a benefit from pembrolizumab for patients with both node-negative disease (pCR, 64.9% vs. 58.6% in the placebo arm) and node-positive disease (64.8% vs. 44.1%, respectively).
pCR rates were also superior with pembrolizumab versus placebo in patients who were PD-L1 negative, defined as a combined positive score (CPS) less than 1 (45.3% vs. 30.3%), as well as PD-L1–positive patients at each of three cutoff values: CPS 1 or greater (68.9% vs. 54.9%), CPS 10 or greater (77.9% vs. 59.8%), and CPS 20 or greater (81.7% vs. 62.5%).
Interestingly, adding pembrolizumab boosted pCR rates both in patients with exposure to a full planned course of chemotherapy (69.7% vs. 55.3% with placebo) and in those who received less than the full course (51.1% vs. 35.7%).
The most common immune-mediated adverse events with the largest between-group differences involved the thyroid, including hypothyroidism (in 14.9% of patients on pembrolizumab and 5.7% of those on placebo), hyperthyroidism (5.1% vs. 1.8%), and thyroiditis (1.7% vs. 1.0%).
“Immune-mediated adverse events are consistent with the known profiles of each regimen, and there’s no new safety signal, no new safety concern at this point in time,” Dr. Schmid said.
Further follow-up will be needed to determine EFS benefit and long-term safety. Investigators plan to perform additional biomarker analyses, including tumor-infiltrating lymphocytes and BRCA, he added.
“Will the KEYNOTE-522 regimen be the new standard of care if approved?” asked invited discussant Kevin Kalinsky, MD, MS, from Columbia University Irving Medical Center in New York. “These are exciting data, both in pCR and early event-free survival. But there’s a risk: a risk of overtreatment, as well as potentially [serious] toxicity in patients with curable disease.”
“The take-home is that this regimen will likely be practice changing in some patients, and with the absence of having a predictor, the benefit may outweigh the risk most in patients with high clinical risk,” he added.
The study was funded by Merck Sharp & Dohme. Dr. Schmid reported advising/consulting for and receiving honoraria from Merck. Dr. Kalinsky disclosed has disclosed that he receives salary from Array Biopharma, has received fees from various companies (not including Merck), and has contracted research with multiple companies, not including Merck.
SOURCE: Schmid P et al. SABCS 2019, Abstract GS3-03.
SAN ANTONIO – Adding pembrolizumab to chemotherapy in the neoadjuvant setting increased the likelihood that women with stage III or early node-positive triple-negative breast cancer (TNBC) would have a pathologic complete response and sustained clinical benefit, results of the phase 3 KEYNOTE-522 study showed.
Among 602 patients evaluable in a definitive pathological complete response (pCR) analysis, the pCR rate was 64.8% for those treated with chemotherapy plus pembrolizumab (Keytruda), compared with 51.2% for patients treated with chemotherapy plus placebo, reported Peter Schmid, MD, PhD, from Barts Cancer Institute in London.
“The addition of neoadjuvant pembrolizumab to chemotherapy provided a significant increase in the path CR rate in all patients, but also a larger magnitude of path CR benefit versus chemotherapy alone in patients with higher-risk disease, such as stage III disease or node-positive early triple-negative breast cancer,” he said at the annual San Antonio Breast Cancer Symposium.
The overall pCR results were originally reported at the 2019 annual meeting of the European Society for Medical Oncology. At SABCS 2019, he reported pCR results for specific subgroups in KEYNOTE-522.
Investigators enrolled patients aged 18 years or older with newly diagnosed TNBC of either stage T1cN1-2, or T2-4N0-2 and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients also had to have at least two separate tumor cores from the primary tumor for assessment of programmed death–ligand 1 (PD-L1).
After stratification for nodal status, tumor size, and carboplatin schedule (once weekly or every 3 weeks), patients were randomized to receive either pembrolizumab 200 mg every 3 weeks or placebo plus neoadjuvant carboplatin and paclitaxel for four 3-week cycles, followed by four cycles of chemotherapy with either doxorubicin or epirubicin plus cyclophosphamide (AC or EC). Patients went on to surgery, then received adjuvant therapy for nine cycles with either pembrolizumab at the neoadjuvant dose and schedule or placebo.
At the first preplanned interim analysis for event-free survival (EFS) based on 1,174 patients followed for a median of 15.5 months, events had occurred in 7.4% of patients on pembro/chemo, compared with 11.8% on placebo/chemo, but this difference did not meet the prespecified P value boundary of .000051 for significance, Dr. Schmid acknowledged.
When the investigators looked at pCR by disease stage, however, they saw the following benefits across all stages in the study:
- Stage IIA: 73.1% with pembrolizumab versus 62.1% with placebo, difference 11%.
- Stage IIB: 56.2% versus 48.4%, difference 7.8%.
- Stage IIIA: 66.7% versus 42.1%, difference 24.6%.
- Stage IIIB: 48.6% versus 23.1%, difference 25.6%.
The greatest benefit for the addition of pembrolizumab to chemotherapy appeared to be in the higher disease stages, Dr. Schmid said.
There was also a benefit from pembrolizumab for patients with both node-negative disease (pCR, 64.9% vs. 58.6% in the placebo arm) and node-positive disease (64.8% vs. 44.1%, respectively).
pCR rates were also superior with pembrolizumab versus placebo in patients who were PD-L1 negative, defined as a combined positive score (CPS) less than 1 (45.3% vs. 30.3%), as well as PD-L1–positive patients at each of three cutoff values: CPS 1 or greater (68.9% vs. 54.9%), CPS 10 or greater (77.9% vs. 59.8%), and CPS 20 or greater (81.7% vs. 62.5%).
Interestingly, adding pembrolizumab boosted pCR rates both in patients with exposure to a full planned course of chemotherapy (69.7% vs. 55.3% with placebo) and in those who received less than the full course (51.1% vs. 35.7%).
The most common immune-mediated adverse events with the largest between-group differences involved the thyroid, including hypothyroidism (in 14.9% of patients on pembrolizumab and 5.7% of those on placebo), hyperthyroidism (5.1% vs. 1.8%), and thyroiditis (1.7% vs. 1.0%).
“Immune-mediated adverse events are consistent with the known profiles of each regimen, and there’s no new safety signal, no new safety concern at this point in time,” Dr. Schmid said.
Further follow-up will be needed to determine EFS benefit and long-term safety. Investigators plan to perform additional biomarker analyses, including tumor-infiltrating lymphocytes and BRCA, he added.
“Will the KEYNOTE-522 regimen be the new standard of care if approved?” asked invited discussant Kevin Kalinsky, MD, MS, from Columbia University Irving Medical Center in New York. “These are exciting data, both in pCR and early event-free survival. But there’s a risk: a risk of overtreatment, as well as potentially [serious] toxicity in patients with curable disease.”
“The take-home is that this regimen will likely be practice changing in some patients, and with the absence of having a predictor, the benefit may outweigh the risk most in patients with high clinical risk,” he added.
The study was funded by Merck Sharp & Dohme. Dr. Schmid reported advising/consulting for and receiving honoraria from Merck. Dr. Kalinsky disclosed has disclosed that he receives salary from Array Biopharma, has received fees from various companies (not including Merck), and has contracted research with multiple companies, not including Merck.
SOURCE: Schmid P et al. SABCS 2019, Abstract GS3-03.
SAN ANTONIO – Adding pembrolizumab to chemotherapy in the neoadjuvant setting increased the likelihood that women with stage III or early node-positive triple-negative breast cancer (TNBC) would have a pathologic complete response and sustained clinical benefit, results of the phase 3 KEYNOTE-522 study showed.
Among 602 patients evaluable in a definitive pathological complete response (pCR) analysis, the pCR rate was 64.8% for those treated with chemotherapy plus pembrolizumab (Keytruda), compared with 51.2% for patients treated with chemotherapy plus placebo, reported Peter Schmid, MD, PhD, from Barts Cancer Institute in London.
“The addition of neoadjuvant pembrolizumab to chemotherapy provided a significant increase in the path CR rate in all patients, but also a larger magnitude of path CR benefit versus chemotherapy alone in patients with higher-risk disease, such as stage III disease or node-positive early triple-negative breast cancer,” he said at the annual San Antonio Breast Cancer Symposium.
The overall pCR results were originally reported at the 2019 annual meeting of the European Society for Medical Oncology. At SABCS 2019, he reported pCR results for specific subgroups in KEYNOTE-522.
Investigators enrolled patients aged 18 years or older with newly diagnosed TNBC of either stage T1cN1-2, or T2-4N0-2 and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients also had to have at least two separate tumor cores from the primary tumor for assessment of programmed death–ligand 1 (PD-L1).
After stratification for nodal status, tumor size, and carboplatin schedule (once weekly or every 3 weeks), patients were randomized to receive either pembrolizumab 200 mg every 3 weeks or placebo plus neoadjuvant carboplatin and paclitaxel for four 3-week cycles, followed by four cycles of chemotherapy with either doxorubicin or epirubicin plus cyclophosphamide (AC or EC). Patients went on to surgery, then received adjuvant therapy for nine cycles with either pembrolizumab at the neoadjuvant dose and schedule or placebo.
At the first preplanned interim analysis for event-free survival (EFS) based on 1,174 patients followed for a median of 15.5 months, events had occurred in 7.4% of patients on pembro/chemo, compared with 11.8% on placebo/chemo, but this difference did not meet the prespecified P value boundary of .000051 for significance, Dr. Schmid acknowledged.
When the investigators looked at pCR by disease stage, however, they saw the following benefits across all stages in the study:
- Stage IIA: 73.1% with pembrolizumab versus 62.1% with placebo, difference 11%.
- Stage IIB: 56.2% versus 48.4%, difference 7.8%.
- Stage IIIA: 66.7% versus 42.1%, difference 24.6%.
- Stage IIIB: 48.6% versus 23.1%, difference 25.6%.
The greatest benefit for the addition of pembrolizumab to chemotherapy appeared to be in the higher disease stages, Dr. Schmid said.
There was also a benefit from pembrolizumab for patients with both node-negative disease (pCR, 64.9% vs. 58.6% in the placebo arm) and node-positive disease (64.8% vs. 44.1%, respectively).
pCR rates were also superior with pembrolizumab versus placebo in patients who were PD-L1 negative, defined as a combined positive score (CPS) less than 1 (45.3% vs. 30.3%), as well as PD-L1–positive patients at each of three cutoff values: CPS 1 or greater (68.9% vs. 54.9%), CPS 10 or greater (77.9% vs. 59.8%), and CPS 20 or greater (81.7% vs. 62.5%).
Interestingly, adding pembrolizumab boosted pCR rates both in patients with exposure to a full planned course of chemotherapy (69.7% vs. 55.3% with placebo) and in those who received less than the full course (51.1% vs. 35.7%).
The most common immune-mediated adverse events with the largest between-group differences involved the thyroid, including hypothyroidism (in 14.9% of patients on pembrolizumab and 5.7% of those on placebo), hyperthyroidism (5.1% vs. 1.8%), and thyroiditis (1.7% vs. 1.0%).
“Immune-mediated adverse events are consistent with the known profiles of each regimen, and there’s no new safety signal, no new safety concern at this point in time,” Dr. Schmid said.
Further follow-up will be needed to determine EFS benefit and long-term safety. Investigators plan to perform additional biomarker analyses, including tumor-infiltrating lymphocytes and BRCA, he added.
“Will the KEYNOTE-522 regimen be the new standard of care if approved?” asked invited discussant Kevin Kalinsky, MD, MS, from Columbia University Irving Medical Center in New York. “These are exciting data, both in pCR and early event-free survival. But there’s a risk: a risk of overtreatment, as well as potentially [serious] toxicity in patients with curable disease.”
“The take-home is that this regimen will likely be practice changing in some patients, and with the absence of having a predictor, the benefit may outweigh the risk most in patients with high clinical risk,” he added.
The study was funded by Merck Sharp & Dohme. Dr. Schmid reported advising/consulting for and receiving honoraria from Merck. Dr. Kalinsky disclosed has disclosed that he receives salary from Array Biopharma, has received fees from various companies (not including Merck), and has contracted research with multiple companies, not including Merck.
SOURCE: Schmid P et al. SABCS 2019, Abstract GS3-03.
REPORTING FROM SABCS 2019
Off-the-shelf cellular therapy shows promise in the lab
ORLANDO – A cellular therapy called FT596 is active against B-cell malignancies and, when combined with rituximab, can be more effective than traditional chimeric antigen receptor (CAR) T cells, preclinical research findings suggest.
FT596 is a universal, anti-CD19 CAR natural killer (NK) cell therapy derived from a master induced pluripotent stem cell (iPSC) line.
FT596 reduced tumor growth in mouse models of leukemia and lymphoma. When combined with rituximab, FT596 was able to overcome CD19 antigen escape.
Jode P. Goodridge, PhD, of Fate Therapeutics in San Diego, presented these results at the annual meeting of the American Society of Hematology.
Dr. Goodridge explained that FT596 begins with a source material, such as a fibroblast, that is reprogrammed into an iPSC progenitor cell. That cell is sorted and expanded into a renewable, homogeneous, pluripotent master iPSC line. The iPSCs are differentiated into CD34 cells, which are differentiated into NK cells. The iPSC-derived NK cells are then modified with the following:
- An anti-CD19 CAR that is optimized for NK-cell biology and contains an NKG2D transmembrane domain, a 2B4 costimulatory domain, and a CD3-zeta signaling domain.
- An interleukin-15 receptor fusion that promotes cell survival and reduces the need for cytokine support.
- A high-affinity 158V, noncleavable CD16 Fc receptor that enhances antibody-dependent cellular cytotoxicity when FT596 is combined with a monoclonal antibody such as rituximab.
Dr. Goodridge presented results with FT596, both alone and in combination with rituximab, in vitro and in vivo.
When compared with no treatment, three doses of FT596 monotherapy reduced tumor growth in a mouse model of leukemia (Nalm6). FT596 plus rituximab reduced tumor growth in a mouse model of lymphoma (Raji), when compared with no treatment or rituximab alone.
Three doses of FT596 proved more effective than a single dose of CD19 CAR T-cell therapy in a mouse model of lymphoma (Raji). FT596 both reduced tumor growth and prolonged survival in the mice.
Lastly, in vitro experiments in Raji cells showed that FT596 plus rituximab can produce deeper responses than primary CAR-T cells, and the combination can prevent antigen escape.
Dr. Goodridge said these results support the phase 1 study of FT596, given as monotherapy or in combination with rituximab or obinutuzumab, in patients with relapsed/refractory B-cell lymphomas or chronic lymphocytic leukemia.
Dr. Goodridge is employed by Fate Therapeutics, the company developing FT596.
SOURCE: Goodridge JP et al. ASH 2019. Abstract 301.
ORLANDO – A cellular therapy called FT596 is active against B-cell malignancies and, when combined with rituximab, can be more effective than traditional chimeric antigen receptor (CAR) T cells, preclinical research findings suggest.
FT596 is a universal, anti-CD19 CAR natural killer (NK) cell therapy derived from a master induced pluripotent stem cell (iPSC) line.
FT596 reduced tumor growth in mouse models of leukemia and lymphoma. When combined with rituximab, FT596 was able to overcome CD19 antigen escape.
Jode P. Goodridge, PhD, of Fate Therapeutics in San Diego, presented these results at the annual meeting of the American Society of Hematology.
Dr. Goodridge explained that FT596 begins with a source material, such as a fibroblast, that is reprogrammed into an iPSC progenitor cell. That cell is sorted and expanded into a renewable, homogeneous, pluripotent master iPSC line. The iPSCs are differentiated into CD34 cells, which are differentiated into NK cells. The iPSC-derived NK cells are then modified with the following:
- An anti-CD19 CAR that is optimized for NK-cell biology and contains an NKG2D transmembrane domain, a 2B4 costimulatory domain, and a CD3-zeta signaling domain.
- An interleukin-15 receptor fusion that promotes cell survival and reduces the need for cytokine support.
- A high-affinity 158V, noncleavable CD16 Fc receptor that enhances antibody-dependent cellular cytotoxicity when FT596 is combined with a monoclonal antibody such as rituximab.
Dr. Goodridge presented results with FT596, both alone and in combination with rituximab, in vitro and in vivo.
When compared with no treatment, three doses of FT596 monotherapy reduced tumor growth in a mouse model of leukemia (Nalm6). FT596 plus rituximab reduced tumor growth in a mouse model of lymphoma (Raji), when compared with no treatment or rituximab alone.
Three doses of FT596 proved more effective than a single dose of CD19 CAR T-cell therapy in a mouse model of lymphoma (Raji). FT596 both reduced tumor growth and prolonged survival in the mice.
Lastly, in vitro experiments in Raji cells showed that FT596 plus rituximab can produce deeper responses than primary CAR-T cells, and the combination can prevent antigen escape.
Dr. Goodridge said these results support the phase 1 study of FT596, given as monotherapy or in combination with rituximab or obinutuzumab, in patients with relapsed/refractory B-cell lymphomas or chronic lymphocytic leukemia.
Dr. Goodridge is employed by Fate Therapeutics, the company developing FT596.
SOURCE: Goodridge JP et al. ASH 2019. Abstract 301.
ORLANDO – A cellular therapy called FT596 is active against B-cell malignancies and, when combined with rituximab, can be more effective than traditional chimeric antigen receptor (CAR) T cells, preclinical research findings suggest.
FT596 is a universal, anti-CD19 CAR natural killer (NK) cell therapy derived from a master induced pluripotent stem cell (iPSC) line.
FT596 reduced tumor growth in mouse models of leukemia and lymphoma. When combined with rituximab, FT596 was able to overcome CD19 antigen escape.
Jode P. Goodridge, PhD, of Fate Therapeutics in San Diego, presented these results at the annual meeting of the American Society of Hematology.
Dr. Goodridge explained that FT596 begins with a source material, such as a fibroblast, that is reprogrammed into an iPSC progenitor cell. That cell is sorted and expanded into a renewable, homogeneous, pluripotent master iPSC line. The iPSCs are differentiated into CD34 cells, which are differentiated into NK cells. The iPSC-derived NK cells are then modified with the following:
- An anti-CD19 CAR that is optimized for NK-cell biology and contains an NKG2D transmembrane domain, a 2B4 costimulatory domain, and a CD3-zeta signaling domain.
- An interleukin-15 receptor fusion that promotes cell survival and reduces the need for cytokine support.
- A high-affinity 158V, noncleavable CD16 Fc receptor that enhances antibody-dependent cellular cytotoxicity when FT596 is combined with a monoclonal antibody such as rituximab.
Dr. Goodridge presented results with FT596, both alone and in combination with rituximab, in vitro and in vivo.
When compared with no treatment, three doses of FT596 monotherapy reduced tumor growth in a mouse model of leukemia (Nalm6). FT596 plus rituximab reduced tumor growth in a mouse model of lymphoma (Raji), when compared with no treatment or rituximab alone.
Three doses of FT596 proved more effective than a single dose of CD19 CAR T-cell therapy in a mouse model of lymphoma (Raji). FT596 both reduced tumor growth and prolonged survival in the mice.
Lastly, in vitro experiments in Raji cells showed that FT596 plus rituximab can produce deeper responses than primary CAR-T cells, and the combination can prevent antigen escape.
Dr. Goodridge said these results support the phase 1 study of FT596, given as monotherapy or in combination with rituximab or obinutuzumab, in patients with relapsed/refractory B-cell lymphomas or chronic lymphocytic leukemia.
Dr. Goodridge is employed by Fate Therapeutics, the company developing FT596.
SOURCE: Goodridge JP et al. ASH 2019. Abstract 301.
REPORTING FROM ASH 2019
Bispecific CAR T-cells yield high response rate in relapsed/refractory myeloma
ORLANDO – A dual-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated a high overall response rate, a long response duration, and manageable safety in patients with relapsed or refractory multiple myeloma, according to an investigator in a phase 1 study.
The overall response rate exceeded 90%, and about three-quarters of patients remained progression-free at 9 months after treatment with the CAR T-cell therapy, which targets both B-cell maturation antigen (BCMA) and CD38, the study investigator reported.
Grade 3 or greater cytokine release syndrome (CRS) occurred in about one-quarter of the patients, and no neurotoxicity was observed, according to investigator Yu Hu, MD, of Tongji Medical College in Hubei, China.
“,” Dr. Hu said in a press conference.
Short-term relapse has been a “major challenge” with current CAR T-cell therapies currently under investigation for myeloma, most of which target BCMA, according to Dr. Hu.
He said the bispecific CAR T-cell therapy under investigation, known as BM38, was designed to target antigen loss and increase persistence of effector cells. According to the investigator, this was the first study to focus on an anti-BCMA and CD38 dual-targeted CAR T-cell therapy for patients with relapsed or refractory multiple myeloma.
Gary J. Schiller, MD, of UCLA Health, who moderated the press conference, said that while dual-targeting is a potentially “attractive” approach in these hard-to-treat patients, further follow-up is needed to see duration of response and to see if antigen escape re-emerges.
“Cellular therapy is costly, in terms of toxicity as well as financial costs, so you would like to see what the durability of responses is before engaging in that as a late-stage therapy, not to mention moving it up front,” Dr. Schiller said in an interview.
The median progression-free survival (PFS) duration had not been reached at the time of this report, though the 9-month PFS rate was 78.87%, according to the data presented by Dr. Hu.
In the phase 1 study, 22 patients received BM38 CAR T-cell infusions following a fludarabine and cyclophosphamide preconditioning regimen. The median patient age was 59 years, and 50% were male. Nearly three-quarters (72%) had a cytogenetic abnormality, and the median number of prior therapies approached four (range, two to nine prior therapies).
Twenty of the patients (90.9%) had a response: 12 who achieved stringent complete remission, 2 with very good partial response, 5 with partial responses, and 1 with a minimal response.
Of 9 patients with extramedullary disease, 8 achieved partial or complete elimination of tumors, Dr. Hu said in his presentation.
Cytokine release syndrome occurred in 20 patients (90.91%), 5 of whom experienced severe cases (22.73%), according to the reported data. There was no observed neurotoxicity, according to the report, while almost all had hematologic toxicities. Three experienced hepatotoxicity and one had nephrotoxicity, according to Dr. Hu.
The phase 1 study was supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project Fund of Hubei Province of China, and Cellyan Therapeutics. The senior author of the study was affiliated with Cellyan Therapeutics. Dr. Hu and coauthors reported that they had no relevant conflicts of interest to declare.
SOURCE: Li C et al. ASH 2019. Abstract 930.
ORLANDO – A dual-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated a high overall response rate, a long response duration, and manageable safety in patients with relapsed or refractory multiple myeloma, according to an investigator in a phase 1 study.
The overall response rate exceeded 90%, and about three-quarters of patients remained progression-free at 9 months after treatment with the CAR T-cell therapy, which targets both B-cell maturation antigen (BCMA) and CD38, the study investigator reported.
Grade 3 or greater cytokine release syndrome (CRS) occurred in about one-quarter of the patients, and no neurotoxicity was observed, according to investigator Yu Hu, MD, of Tongji Medical College in Hubei, China.
“,” Dr. Hu said in a press conference.
Short-term relapse has been a “major challenge” with current CAR T-cell therapies currently under investigation for myeloma, most of which target BCMA, according to Dr. Hu.
He said the bispecific CAR T-cell therapy under investigation, known as BM38, was designed to target antigen loss and increase persistence of effector cells. According to the investigator, this was the first study to focus on an anti-BCMA and CD38 dual-targeted CAR T-cell therapy for patients with relapsed or refractory multiple myeloma.
Gary J. Schiller, MD, of UCLA Health, who moderated the press conference, said that while dual-targeting is a potentially “attractive” approach in these hard-to-treat patients, further follow-up is needed to see duration of response and to see if antigen escape re-emerges.
“Cellular therapy is costly, in terms of toxicity as well as financial costs, so you would like to see what the durability of responses is before engaging in that as a late-stage therapy, not to mention moving it up front,” Dr. Schiller said in an interview.
The median progression-free survival (PFS) duration had not been reached at the time of this report, though the 9-month PFS rate was 78.87%, according to the data presented by Dr. Hu.
In the phase 1 study, 22 patients received BM38 CAR T-cell infusions following a fludarabine and cyclophosphamide preconditioning regimen. The median patient age was 59 years, and 50% were male. Nearly three-quarters (72%) had a cytogenetic abnormality, and the median number of prior therapies approached four (range, two to nine prior therapies).
Twenty of the patients (90.9%) had a response: 12 who achieved stringent complete remission, 2 with very good partial response, 5 with partial responses, and 1 with a minimal response.
Of 9 patients with extramedullary disease, 8 achieved partial or complete elimination of tumors, Dr. Hu said in his presentation.
Cytokine release syndrome occurred in 20 patients (90.91%), 5 of whom experienced severe cases (22.73%), according to the reported data. There was no observed neurotoxicity, according to the report, while almost all had hematologic toxicities. Three experienced hepatotoxicity and one had nephrotoxicity, according to Dr. Hu.
The phase 1 study was supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project Fund of Hubei Province of China, and Cellyan Therapeutics. The senior author of the study was affiliated with Cellyan Therapeutics. Dr. Hu and coauthors reported that they had no relevant conflicts of interest to declare.
SOURCE: Li C et al. ASH 2019. Abstract 930.
ORLANDO – A dual-targeted chimeric antigen receptor (CAR) T-cell therapy has demonstrated a high overall response rate, a long response duration, and manageable safety in patients with relapsed or refractory multiple myeloma, according to an investigator in a phase 1 study.
The overall response rate exceeded 90%, and about three-quarters of patients remained progression-free at 9 months after treatment with the CAR T-cell therapy, which targets both B-cell maturation antigen (BCMA) and CD38, the study investigator reported.
Grade 3 or greater cytokine release syndrome (CRS) occurred in about one-quarter of the patients, and no neurotoxicity was observed, according to investigator Yu Hu, MD, of Tongji Medical College in Hubei, China.
“,” Dr. Hu said in a press conference.
Short-term relapse has been a “major challenge” with current CAR T-cell therapies currently under investigation for myeloma, most of which target BCMA, according to Dr. Hu.
He said the bispecific CAR T-cell therapy under investigation, known as BM38, was designed to target antigen loss and increase persistence of effector cells. According to the investigator, this was the first study to focus on an anti-BCMA and CD38 dual-targeted CAR T-cell therapy for patients with relapsed or refractory multiple myeloma.
Gary J. Schiller, MD, of UCLA Health, who moderated the press conference, said that while dual-targeting is a potentially “attractive” approach in these hard-to-treat patients, further follow-up is needed to see duration of response and to see if antigen escape re-emerges.
“Cellular therapy is costly, in terms of toxicity as well as financial costs, so you would like to see what the durability of responses is before engaging in that as a late-stage therapy, not to mention moving it up front,” Dr. Schiller said in an interview.
The median progression-free survival (PFS) duration had not been reached at the time of this report, though the 9-month PFS rate was 78.87%, according to the data presented by Dr. Hu.
In the phase 1 study, 22 patients received BM38 CAR T-cell infusions following a fludarabine and cyclophosphamide preconditioning regimen. The median patient age was 59 years, and 50% were male. Nearly three-quarters (72%) had a cytogenetic abnormality, and the median number of prior therapies approached four (range, two to nine prior therapies).
Twenty of the patients (90.9%) had a response: 12 who achieved stringent complete remission, 2 with very good partial response, 5 with partial responses, and 1 with a minimal response.
Of 9 patients with extramedullary disease, 8 achieved partial or complete elimination of tumors, Dr. Hu said in his presentation.
Cytokine release syndrome occurred in 20 patients (90.91%), 5 of whom experienced severe cases (22.73%), according to the reported data. There was no observed neurotoxicity, according to the report, while almost all had hematologic toxicities. Three experienced hepatotoxicity and one had nephrotoxicity, according to Dr. Hu.
The phase 1 study was supported by the National Natural Science Foundation of China, the Major Technological Innovation Special Project Fund of Hubei Province of China, and Cellyan Therapeutics. The senior author of the study was affiliated with Cellyan Therapeutics. Dr. Hu and coauthors reported that they had no relevant conflicts of interest to declare.
SOURCE: Li C et al. ASH 2019. Abstract 930.
REPORTING FROM ASH 2019
High complete response rate seen with novel CAR-T for myeloma
ORLANDO – A novel chimeric antigen receptor T (CAR T) cell construct is associated with deep clinical responses in patients with multiple myeloma for whom prior lines of therapy – some numbering in the double digits – have failed.
Among 29 patients with multiple myeloma enrolled in a phase 1b/2 trial of JNJ-4528, the overall response rate (ORR) at 6 months median follow-up was 100%, including 69% complete responses, with 27 patients remaining free of disease progression at a median of 6 months, reported Deepu Madduri, MD, of Icahn School of Medicine at Mount Sinai, New York.
“These are very heavily pretreated patients, and so getting early and deep responses is quite amazing,” she said at a briefing prior to presentation of the data at the annual meeting of the American Society of Hematology.
JNJ-4528 is a second-generation CAR T containing two single-domain antibodies targeted against B-cell maturation protein (BCMA). As previously reported, an identical CAR T cell construct showed a high overall response with manageable toxicities in 74 patients with relapsed/refractory multiple myeloma. JNJ-4528 was granted a breakthrough therapy designation for relapsed/refractory multiple myeloma by the Food and Drug Administration on Dec. 6, 2019, and a priority medicines (PRIME) designation by the European Medicines Agency in April 2019.
BCMA was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells. Several research groups are currently investigating CAR T cells or monoclonal antibodies targeted to BCMA. The product closest to receiving FDA approval is likely BB2121.
At ASH 2019, Dr. Madduri presented results from the phase 1b portion of the CARTITUDE-1 trial. The investigators enrolled patients with multiple myeloma with measurable diseases as assessed by M-protein or serum free light chain levels who had experienced disease progression on at least 3 prior lines of therapy, or whose disease was refractory to at least two lines of therapy with a proteasome inhibitor, immunomodulatory drug (IMiD), and an anti-CD38 antibody.
Patients underwent apheresis for T-cell collection, with bridging therapy allowed until the expanded T cells could be delivered.
Following T-cell depletion with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 over 3 days, patients received a single weight-based infusion (compared with fixed-dose infusions used with other CAR T cell constructs).
The dose was targeted at 0.75x106 CAR-positive cells/kg, with a target range of 0.5–1.0x106, administered 5-7 days after the start of the conditioning regimen.
A total of 29 patients, median age 60, were evaluable for the safety and efficacy endpoints. One-fourth of the patients had a high-risk cytogenetic profile. The patients had received a median of 5 prior lines of therapy, with one patient receiving 18 prior lines. Of the 29 patients, 25 (86%) had previously undergone autologous transplantation.
As noted before, the ORR after a median follow-up of 6 months was 100%, with 69% completer responses, 17% very good partial responses, and 14% partial responses. The median time to complete response was 1 month (range 1 to 9 months). All but two patients remained free of disease progression at the median 6-month follow-up.
Nearly all patients (27) developed cytokine release syndrome (CRS), and one patient with prolonged grade 4 CRS died from related complications 99 days after infusion.
The median time to onset of CRS was 7 days with more than 90% of cases occurring between days 5 and 9.
Neurotoxicities, specifically immune effector cell–associated neurotoxicity syndrome (ICANS), were infrequent in CRS, and when they did occur were generally low grade, with only 1 grade 3 ICANS event.
Asked in an interview whether the impressive response rates seen with JNJ-4528 might persist over time, Dr. Madduri acknowledged that follow-up is still relatively short.
“This product is unique in that has a CD8 central memory phenotype preferentially, and we’re hoping that this would play a central role in the durability of response because they’re memory cells, but I think at this time we don’t know,” she said.
The CARTITUDE-1 trial is funded by Janssen Research & Development. Dr. Madduri disclosed serving as a consultant to Janssen and to Takeda, Foundation Medicine, AbbVie, and Celgene.
SOURCE: Madduri D et al. ASH 2019. Abstract 577.
ORLANDO – A novel chimeric antigen receptor T (CAR T) cell construct is associated with deep clinical responses in patients with multiple myeloma for whom prior lines of therapy – some numbering in the double digits – have failed.
Among 29 patients with multiple myeloma enrolled in a phase 1b/2 trial of JNJ-4528, the overall response rate (ORR) at 6 months median follow-up was 100%, including 69% complete responses, with 27 patients remaining free of disease progression at a median of 6 months, reported Deepu Madduri, MD, of Icahn School of Medicine at Mount Sinai, New York.
“These are very heavily pretreated patients, and so getting early and deep responses is quite amazing,” she said at a briefing prior to presentation of the data at the annual meeting of the American Society of Hematology.
JNJ-4528 is a second-generation CAR T containing two single-domain antibodies targeted against B-cell maturation protein (BCMA). As previously reported, an identical CAR T cell construct showed a high overall response with manageable toxicities in 74 patients with relapsed/refractory multiple myeloma. JNJ-4528 was granted a breakthrough therapy designation for relapsed/refractory multiple myeloma by the Food and Drug Administration on Dec. 6, 2019, and a priority medicines (PRIME) designation by the European Medicines Agency in April 2019.
BCMA was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells. Several research groups are currently investigating CAR T cells or monoclonal antibodies targeted to BCMA. The product closest to receiving FDA approval is likely BB2121.
At ASH 2019, Dr. Madduri presented results from the phase 1b portion of the CARTITUDE-1 trial. The investigators enrolled patients with multiple myeloma with measurable diseases as assessed by M-protein or serum free light chain levels who had experienced disease progression on at least 3 prior lines of therapy, or whose disease was refractory to at least two lines of therapy with a proteasome inhibitor, immunomodulatory drug (IMiD), and an anti-CD38 antibody.
Patients underwent apheresis for T-cell collection, with bridging therapy allowed until the expanded T cells could be delivered.
Following T-cell depletion with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 over 3 days, patients received a single weight-based infusion (compared with fixed-dose infusions used with other CAR T cell constructs).
The dose was targeted at 0.75x106 CAR-positive cells/kg, with a target range of 0.5–1.0x106, administered 5-7 days after the start of the conditioning regimen.
A total of 29 patients, median age 60, were evaluable for the safety and efficacy endpoints. One-fourth of the patients had a high-risk cytogenetic profile. The patients had received a median of 5 prior lines of therapy, with one patient receiving 18 prior lines. Of the 29 patients, 25 (86%) had previously undergone autologous transplantation.
As noted before, the ORR after a median follow-up of 6 months was 100%, with 69% completer responses, 17% very good partial responses, and 14% partial responses. The median time to complete response was 1 month (range 1 to 9 months). All but two patients remained free of disease progression at the median 6-month follow-up.
Nearly all patients (27) developed cytokine release syndrome (CRS), and one patient with prolonged grade 4 CRS died from related complications 99 days after infusion.
The median time to onset of CRS was 7 days with more than 90% of cases occurring between days 5 and 9.
Neurotoxicities, specifically immune effector cell–associated neurotoxicity syndrome (ICANS), were infrequent in CRS, and when they did occur were generally low grade, with only 1 grade 3 ICANS event.
Asked in an interview whether the impressive response rates seen with JNJ-4528 might persist over time, Dr. Madduri acknowledged that follow-up is still relatively short.
“This product is unique in that has a CD8 central memory phenotype preferentially, and we’re hoping that this would play a central role in the durability of response because they’re memory cells, but I think at this time we don’t know,” she said.
The CARTITUDE-1 trial is funded by Janssen Research & Development. Dr. Madduri disclosed serving as a consultant to Janssen and to Takeda, Foundation Medicine, AbbVie, and Celgene.
SOURCE: Madduri D et al. ASH 2019. Abstract 577.
ORLANDO – A novel chimeric antigen receptor T (CAR T) cell construct is associated with deep clinical responses in patients with multiple myeloma for whom prior lines of therapy – some numbering in the double digits – have failed.
Among 29 patients with multiple myeloma enrolled in a phase 1b/2 trial of JNJ-4528, the overall response rate (ORR) at 6 months median follow-up was 100%, including 69% complete responses, with 27 patients remaining free of disease progression at a median of 6 months, reported Deepu Madduri, MD, of Icahn School of Medicine at Mount Sinai, New York.
“These are very heavily pretreated patients, and so getting early and deep responses is quite amazing,” she said at a briefing prior to presentation of the data at the annual meeting of the American Society of Hematology.
JNJ-4528 is a second-generation CAR T containing two single-domain antibodies targeted against B-cell maturation protein (BCMA). As previously reported, an identical CAR T cell construct showed a high overall response with manageable toxicities in 74 patients with relapsed/refractory multiple myeloma. JNJ-4528 was granted a breakthrough therapy designation for relapsed/refractory multiple myeloma by the Food and Drug Administration on Dec. 6, 2019, and a priority medicines (PRIME) designation by the European Medicines Agency in April 2019.
BCMA was first described in myeloma in 2004 as a mechanism for the growth and survival of malignant plasma cells. Several research groups are currently investigating CAR T cells or monoclonal antibodies targeted to BCMA. The product closest to receiving FDA approval is likely BB2121.
At ASH 2019, Dr. Madduri presented results from the phase 1b portion of the CARTITUDE-1 trial. The investigators enrolled patients with multiple myeloma with measurable diseases as assessed by M-protein or serum free light chain levels who had experienced disease progression on at least 3 prior lines of therapy, or whose disease was refractory to at least two lines of therapy with a proteasome inhibitor, immunomodulatory drug (IMiD), and an anti-CD38 antibody.
Patients underwent apheresis for T-cell collection, with bridging therapy allowed until the expanded T cells could be delivered.
Following T-cell depletion with cyclophosphamide 300 mg/m2 and fludarabine 30 mg/m2 over 3 days, patients received a single weight-based infusion (compared with fixed-dose infusions used with other CAR T cell constructs).
The dose was targeted at 0.75x106 CAR-positive cells/kg, with a target range of 0.5–1.0x106, administered 5-7 days after the start of the conditioning regimen.
A total of 29 patients, median age 60, were evaluable for the safety and efficacy endpoints. One-fourth of the patients had a high-risk cytogenetic profile. The patients had received a median of 5 prior lines of therapy, with one patient receiving 18 prior lines. Of the 29 patients, 25 (86%) had previously undergone autologous transplantation.
As noted before, the ORR after a median follow-up of 6 months was 100%, with 69% completer responses, 17% very good partial responses, and 14% partial responses. The median time to complete response was 1 month (range 1 to 9 months). All but two patients remained free of disease progression at the median 6-month follow-up.
Nearly all patients (27) developed cytokine release syndrome (CRS), and one patient with prolonged grade 4 CRS died from related complications 99 days after infusion.
The median time to onset of CRS was 7 days with more than 90% of cases occurring between days 5 and 9.
Neurotoxicities, specifically immune effector cell–associated neurotoxicity syndrome (ICANS), were infrequent in CRS, and when they did occur were generally low grade, with only 1 grade 3 ICANS event.
Asked in an interview whether the impressive response rates seen with JNJ-4528 might persist over time, Dr. Madduri acknowledged that follow-up is still relatively short.
“This product is unique in that has a CD8 central memory phenotype preferentially, and we’re hoping that this would play a central role in the durability of response because they’re memory cells, but I think at this time we don’t know,” she said.
The CARTITUDE-1 trial is funded by Janssen Research & Development. Dr. Madduri disclosed serving as a consultant to Janssen and to Takeda, Foundation Medicine, AbbVie, and Celgene.
SOURCE: Madduri D et al. ASH 2019. Abstract 577.
REPORTING FROM ASH 2019
Patient-reported outcomes support first-line pembrolizumab for NSCLC
Patient-reported outcomes support pembrolizumab plus chemotherapy for first-line treatment of metastatic non–small cell lung cancer (NSCLC), based on results from the KEYNOTE-407 trial.
At week 18, patients given pembrolizumab more often reported clinically meaningful health-related quality of life improvements than those in the placebo group, according to lead author Julien Mazieres, MD, PhD, of Paul Sabatier University in Toulouse, France, and colleagues.
Writing in the Journal of Clinical Oncology, the investigators explained that these findings build upon previously published results from KEYNOTE-407, which showed that adding pembrolizumab to chemotherapy in the first line could extend both progression-free and overall survival among patients with NSCLC. The benefits to quality of life associated with pembrolizumab align with similar findings from the KEYNOTE-024 and KEYNOTE-189 trials, they added.
The present analysis involved 559 patients with treatment-naive metastatic NSCLC. Patients were randomized to receive 4 cycles of placebo or pembrolizumab once every 3 weeks with carboplatin-based chemotherapy, followed by pembrolizumab or placebo for an additional 31 cycles. Health-related quality of life was assessed by two measures: the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and QLQ–Lung Cancer Module 13 (QLQ-LC13).
Of the 559 patients enrolled, 554 completed at least one QLQ-C30 assessment and 553 completed at least one QLQ-LC13 assessment. These quality of life scores were compared temporally within treatment groups, from baseline to week 9 and week 18, and between groups. The investigators also analyzed median time to deterioration in chest pain, cough, and dyspnea.
Results showed that patients in the pembrolizumab group had statistically significant improvements in patient-reported outcomes over time and more frequently reported improvements than patients in the placebo group. Specifically, in the pembrolizumab group, least-squares mean score improved from baseline to week 9 (1.8) and week 18 (4.3); in comparison, least-squares mean score deteriorated in the placebo group from baseline to week 9 (–1.8) and week 18 (–0.57). Compared with placebo, treatment with pembrolizumab was associated with a least-squares mean change of 3.6 at week 9 (nominal P = .0337) and 4.9 at week 18 (nominal P = .0060). Stated differently, at week 18, compared with placebo, more patients in the pembrolizumab group reported clinically meaningful improvements in health-related quality of life (36.2% vs. 27.7%), and relatively fewer reported deterioration (22.8% vs. 31.3%). Median time to deterioration in symptoms was not reached in either treatment arm.
“These health-related quality of life findings, along with the improved efficacy (including overall survival benefit) of pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel, support its use as a first-line treatment of metastatic squamous NSCLC, regardless of programmed death–ligand 1 expression,” the investigators concluded.
The study was funded by Merck. The investigators reported additional relationships with Novartis, Genentech, Pfizer, and others.
SOURCE: Mazieres J et al. J Clin Oncol. 2019 Nov 21. doi: 10.1200/JCO.19.01348.
Patient-reported outcomes support pembrolizumab plus chemotherapy for first-line treatment of metastatic non–small cell lung cancer (NSCLC), based on results from the KEYNOTE-407 trial.
At week 18, patients given pembrolizumab more often reported clinically meaningful health-related quality of life improvements than those in the placebo group, according to lead author Julien Mazieres, MD, PhD, of Paul Sabatier University in Toulouse, France, and colleagues.
Writing in the Journal of Clinical Oncology, the investigators explained that these findings build upon previously published results from KEYNOTE-407, which showed that adding pembrolizumab to chemotherapy in the first line could extend both progression-free and overall survival among patients with NSCLC. The benefits to quality of life associated with pembrolizumab align with similar findings from the KEYNOTE-024 and KEYNOTE-189 trials, they added.
The present analysis involved 559 patients with treatment-naive metastatic NSCLC. Patients were randomized to receive 4 cycles of placebo or pembrolizumab once every 3 weeks with carboplatin-based chemotherapy, followed by pembrolizumab or placebo for an additional 31 cycles. Health-related quality of life was assessed by two measures: the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and QLQ–Lung Cancer Module 13 (QLQ-LC13).
Of the 559 patients enrolled, 554 completed at least one QLQ-C30 assessment and 553 completed at least one QLQ-LC13 assessment. These quality of life scores were compared temporally within treatment groups, from baseline to week 9 and week 18, and between groups. The investigators also analyzed median time to deterioration in chest pain, cough, and dyspnea.
Results showed that patients in the pembrolizumab group had statistically significant improvements in patient-reported outcomes over time and more frequently reported improvements than patients in the placebo group. Specifically, in the pembrolizumab group, least-squares mean score improved from baseline to week 9 (1.8) and week 18 (4.3); in comparison, least-squares mean score deteriorated in the placebo group from baseline to week 9 (–1.8) and week 18 (–0.57). Compared with placebo, treatment with pembrolizumab was associated with a least-squares mean change of 3.6 at week 9 (nominal P = .0337) and 4.9 at week 18 (nominal P = .0060). Stated differently, at week 18, compared with placebo, more patients in the pembrolizumab group reported clinically meaningful improvements in health-related quality of life (36.2% vs. 27.7%), and relatively fewer reported deterioration (22.8% vs. 31.3%). Median time to deterioration in symptoms was not reached in either treatment arm.
“These health-related quality of life findings, along with the improved efficacy (including overall survival benefit) of pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel, support its use as a first-line treatment of metastatic squamous NSCLC, regardless of programmed death–ligand 1 expression,” the investigators concluded.
The study was funded by Merck. The investigators reported additional relationships with Novartis, Genentech, Pfizer, and others.
SOURCE: Mazieres J et al. J Clin Oncol. 2019 Nov 21. doi: 10.1200/JCO.19.01348.
Patient-reported outcomes support pembrolizumab plus chemotherapy for first-line treatment of metastatic non–small cell lung cancer (NSCLC), based on results from the KEYNOTE-407 trial.
At week 18, patients given pembrolizumab more often reported clinically meaningful health-related quality of life improvements than those in the placebo group, according to lead author Julien Mazieres, MD, PhD, of Paul Sabatier University in Toulouse, France, and colleagues.
Writing in the Journal of Clinical Oncology, the investigators explained that these findings build upon previously published results from KEYNOTE-407, which showed that adding pembrolizumab to chemotherapy in the first line could extend both progression-free and overall survival among patients with NSCLC. The benefits to quality of life associated with pembrolizumab align with similar findings from the KEYNOTE-024 and KEYNOTE-189 trials, they added.
The present analysis involved 559 patients with treatment-naive metastatic NSCLC. Patients were randomized to receive 4 cycles of placebo or pembrolizumab once every 3 weeks with carboplatin-based chemotherapy, followed by pembrolizumab or placebo for an additional 31 cycles. Health-related quality of life was assessed by two measures: the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and QLQ–Lung Cancer Module 13 (QLQ-LC13).
Of the 559 patients enrolled, 554 completed at least one QLQ-C30 assessment and 553 completed at least one QLQ-LC13 assessment. These quality of life scores were compared temporally within treatment groups, from baseline to week 9 and week 18, and between groups. The investigators also analyzed median time to deterioration in chest pain, cough, and dyspnea.
Results showed that patients in the pembrolizumab group had statistically significant improvements in patient-reported outcomes over time and more frequently reported improvements than patients in the placebo group. Specifically, in the pembrolizumab group, least-squares mean score improved from baseline to week 9 (1.8) and week 18 (4.3); in comparison, least-squares mean score deteriorated in the placebo group from baseline to week 9 (–1.8) and week 18 (–0.57). Compared with placebo, treatment with pembrolizumab was associated with a least-squares mean change of 3.6 at week 9 (nominal P = .0337) and 4.9 at week 18 (nominal P = .0060). Stated differently, at week 18, compared with placebo, more patients in the pembrolizumab group reported clinically meaningful improvements in health-related quality of life (36.2% vs. 27.7%), and relatively fewer reported deterioration (22.8% vs. 31.3%). Median time to deterioration in symptoms was not reached in either treatment arm.
“These health-related quality of life findings, along with the improved efficacy (including overall survival benefit) of pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel, support its use as a first-line treatment of metastatic squamous NSCLC, regardless of programmed death–ligand 1 expression,” the investigators concluded.
The study was funded by Merck. The investigators reported additional relationships with Novartis, Genentech, Pfizer, and others.
SOURCE: Mazieres J et al. J Clin Oncol. 2019 Nov 21. doi: 10.1200/JCO.19.01348.
FROM THE JOURNAL OF CLINICAL ONCOLOGY