ALL

A disease risk index is now available for pediatric patients with acute myeloid leukemia or acute lymphoblastic leukemia who undergo allogeneic hematopoietic stem cell transplantation.

The model, which was developed and validated using data from more than 2,000 patients, stratifies probabilities of leukemia-free survival (LFS) into four risk groups for acute myeloid leukemia (AML) and three risk groups for acute lymphoblastic leukemia (ALL), reported lead author Muna Qayed, MD, of Emory University, Atlanta, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“The outcome of stem cell transplantation for hematologic malignancy is influenced by disease type, cytogenetics, and disease status at transplantation,” Dr. Qayed said. “In adults, these attributes were used to develop the disease risk index, or DRI, that can stratify patients for overall survival for purposes such as prognostication or clinical trial entry.”

But no such model exists for pediatric patients, Dr. Qayed said, noting that the adult DRI was found to be inaccurate when applied to children.

“[T]he [adult] DRI did not differentiate [pediatric] patients by overall survival,” Dr. Qayed said. “Therefore, knowing that pediatric AML and ALL differ biologically from adult leukemia, and further, treatment strategies differ between adults and children, we aimed to develop a pediatric-specific DRI.”

This involved analysis of data from 1,135 children with AML and 1,228 children with ALL who underwent transplantation between 2008 and 2017. All patients had myeloablative conditioning, and 75% received an unrelated donor graft. Haploidentical transplants were excluded because of small sample size.

Analyses were conducted in AML and ALL cohorts, with patients in each population randomized to training and validation subgroups in a 1:1 ratio. The primary outcome was LFS. Cox regression models were used to identify significant characteristics, which were then integrated into a prognostic scoring system for the training groups. These scoring systems were then tested in the validation subgroups. Maximum likelihood was used to identify age cutoffs, which were 3 years for AML and 2 years for ALL.

In both cohorts, disease status at transplantation was characterized by complete remission and minimal residual disease status.

In the AML cohort, approximately one-third of patients were in first complete remission with negative minimal residual disease. Risk was stratified into four groups, including good, intermediate, high, and very high risk, with respective 5-year LFS probabilities of 81%, 56%, 44%, and 21%. Independent predictors of poorer outcome included unfavorable cytogenetics, first or second complete remission with minimal residual disease positivity, relapse at transplantation, and age less than 3 years.

In the ALL cohort, risk was stratified into three risk tiers: good, intermediate, and high, with 5-year LFS probabilities of 68%, 50%, and 15%, respectively. Independent predictors of poorer outcome included age less than 2 years, relapse at transplantation, and second complete remission regardless of minimal residual disease status.

The models for each disease also predicted overall survival.

For AML, hazard ratios, ascending from good to very-high-risk tiers, were 1.00, 3.52, 4.67, and 8.62. For ALL risk tiers, ascending hazard ratios were 1.00, 2.16, and 3.86.

“In summary, the pediatric disease risk index validated for leukemia-free survival and overall survival successfully stratifies children with acute leukemia at the time of transplantation,” Dr. Qayed said.

She concluded her presentation by highlighting the practicality and relevance of the new scoring system.

“The components included in the scoring system used information that is readily available pretransplantation, lending support to the deliverability of the prognostic scoring system,” Dr. Qayed said. “It can further be used for improved interpretation of multicenter data and in clinical trials for risk stratification.”

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., first emphasized the clinical importance of an accurate disease risk index for pediatric patients.

“When going into transplant, the No. 1 question that all parents will ask is: ‘Will my child be cured?’ ” she said.

According to Dr. Shah, the risk model developed by Dr. Qayed and colleagues is built on a strong foundation, including adequate sample size, comprehensive disease characterization, exclusion of patients that did not undergo myeloablative conditioning, and use of minimal residual disease status.

Still, more work is needed, Dr. Shah said.

“This DRI will need to be prospectively tested and compared to other established risk factors. For instance, minimal residual disease alone can be further stratified and has a significant role in establishing risk for posttransplant relapse. And the development of acute graft-versus-host disease also plays an important role in posttransplant relapse.”

Dr. Shah went on to outline potential areas of improvement.

“[F]uture directions for this study could include incorporation of early posttransplant events like graft-versus-host disease, potential stratification of the minimal residual disease results among those patients in complete remission, and potential application of this DRI to the adolescent and young adult population, which may have slight variation even from the adult DRI.”The study was funded by the National Institutes of Health. The investigators disclosed no conflicts of interest

SOURCE: Qayed M et al. ASCO 2020, Abstract 7503.

A disease risk index is now available for pediatric patients with acute myeloid leukemia or acute lymphoblastic leukemia who undergo allogeneic hematopoietic stem cell transplantation.

The model, which was developed and validated using data from more than 2,000 patients, stratifies probabilities of leukemia-free survival (LFS) into four risk groups for acute myeloid leukemia (AML) and three risk groups for acute lymphoblastic leukemia (ALL), reported lead author Muna Qayed, MD, of Emory University, Atlanta, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“The outcome of stem cell transplantation for hematologic malignancy is influenced by disease type, cytogenetics, and disease status at transplantation,” Dr. Qayed said. “In adults, these attributes were used to develop the disease risk index, or DRI, that can stratify patients for overall survival for purposes such as prognostication or clinical trial entry.”

But no such model exists for pediatric patients, Dr. Qayed said, noting that the adult DRI was found to be inaccurate when applied to children.

“[T]he [adult] DRI did not differentiate [pediatric] patients by overall survival,” Dr. Qayed said. “Therefore, knowing that pediatric AML and ALL differ biologically from adult leukemia, and further, treatment strategies differ between adults and children, we aimed to develop a pediatric-specific DRI.”

This involved analysis of data from 1,135 children with AML and 1,228 children with ALL who underwent transplantation between 2008 and 2017. All patients had myeloablative conditioning, and 75% received an unrelated donor graft. Haploidentical transplants were excluded because of small sample size.

Analyses were conducted in AML and ALL cohorts, with patients in each population randomized to training and validation subgroups in a 1:1 ratio. The primary outcome was LFS. Cox regression models were used to identify significant characteristics, which were then integrated into a prognostic scoring system for the training groups. These scoring systems were then tested in the validation subgroups. Maximum likelihood was used to identify age cutoffs, which were 3 years for AML and 2 years for ALL.

In both cohorts, disease status at transplantation was characterized by complete remission and minimal residual disease status.

In the AML cohort, approximately one-third of patients were in first complete remission with negative minimal residual disease. Risk was stratified into four groups, including good, intermediate, high, and very high risk, with respective 5-year LFS probabilities of 81%, 56%, 44%, and 21%. Independent predictors of poorer outcome included unfavorable cytogenetics, first or second complete remission with minimal residual disease positivity, relapse at transplantation, and age less than 3 years.

In the ALL cohort, risk was stratified into three risk tiers: good, intermediate, and high, with 5-year LFS probabilities of 68%, 50%, and 15%, respectively. Independent predictors of poorer outcome included age less than 2 years, relapse at transplantation, and second complete remission regardless of minimal residual disease status.

The models for each disease also predicted overall survival.

For AML, hazard ratios, ascending from good to very-high-risk tiers, were 1.00, 3.52, 4.67, and 8.62. For ALL risk tiers, ascending hazard ratios were 1.00, 2.16, and 3.86.

“In summary, the pediatric disease risk index validated for leukemia-free survival and overall survival successfully stratifies children with acute leukemia at the time of transplantation,” Dr. Qayed said.

She concluded her presentation by highlighting the practicality and relevance of the new scoring system.

“The components included in the scoring system used information that is readily available pretransplantation, lending support to the deliverability of the prognostic scoring system,” Dr. Qayed said. “It can further be used for improved interpretation of multicenter data and in clinical trials for risk stratification.”

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., first emphasized the clinical importance of an accurate disease risk index for pediatric patients.

“When going into transplant, the No. 1 question that all parents will ask is: ‘Will my child be cured?’ ” she said.

According to Dr. Shah, the risk model developed by Dr. Qayed and colleagues is built on a strong foundation, including adequate sample size, comprehensive disease characterization, exclusion of patients that did not undergo myeloablative conditioning, and use of minimal residual disease status.

Still, more work is needed, Dr. Shah said.

“This DRI will need to be prospectively tested and compared to other established risk factors. For instance, minimal residual disease alone can be further stratified and has a significant role in establishing risk for posttransplant relapse. And the development of acute graft-versus-host disease also plays an important role in posttransplant relapse.”

Dr. Shah went on to outline potential areas of improvement.

“[F]uture directions for this study could include incorporation of early posttransplant events like graft-versus-host disease, potential stratification of the minimal residual disease results among those patients in complete remission, and potential application of this DRI to the adolescent and young adult population, which may have slight variation even from the adult DRI.”The study was funded by the National Institutes of Health. The investigators disclosed no conflicts of interest

SOURCE: Qayed M et al. ASCO 2020, Abstract 7503.

A disease risk index is now available for pediatric patients with acute myeloid leukemia or acute lymphoblastic leukemia who undergo allogeneic hematopoietic stem cell transplantation.

The model, which was developed and validated using data from more than 2,000 patients, stratifies probabilities of leukemia-free survival (LFS) into four risk groups for acute myeloid leukemia (AML) and three risk groups for acute lymphoblastic leukemia (ALL), reported lead author Muna Qayed, MD, of Emory University, Atlanta, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

“The outcome of stem cell transplantation for hematologic malignancy is influenced by disease type, cytogenetics, and disease status at transplantation,” Dr. Qayed said. “In adults, these attributes were used to develop the disease risk index, or DRI, that can stratify patients for overall survival for purposes such as prognostication or clinical trial entry.”

But no such model exists for pediatric patients, Dr. Qayed said, noting that the adult DRI was found to be inaccurate when applied to children.

“[T]he [adult] DRI did not differentiate [pediatric] patients by overall survival,” Dr. Qayed said. “Therefore, knowing that pediatric AML and ALL differ biologically from adult leukemia, and further, treatment strategies differ between adults and children, we aimed to develop a pediatric-specific DRI.”

This involved analysis of data from 1,135 children with AML and 1,228 children with ALL who underwent transplantation between 2008 and 2017. All patients had myeloablative conditioning, and 75% received an unrelated donor graft. Haploidentical transplants were excluded because of small sample size.

Analyses were conducted in AML and ALL cohorts, with patients in each population randomized to training and validation subgroups in a 1:1 ratio. The primary outcome was LFS. Cox regression models were used to identify significant characteristics, which were then integrated into a prognostic scoring system for the training groups. These scoring systems were then tested in the validation subgroups. Maximum likelihood was used to identify age cutoffs, which were 3 years for AML and 2 years for ALL.

In both cohorts, disease status at transplantation was characterized by complete remission and minimal residual disease status.

In the AML cohort, approximately one-third of patients were in first complete remission with negative minimal residual disease. Risk was stratified into four groups, including good, intermediate, high, and very high risk, with respective 5-year LFS probabilities of 81%, 56%, 44%, and 21%. Independent predictors of poorer outcome included unfavorable cytogenetics, first or second complete remission with minimal residual disease positivity, relapse at transplantation, and age less than 3 years.

In the ALL cohort, risk was stratified into three risk tiers: good, intermediate, and high, with 5-year LFS probabilities of 68%, 50%, and 15%, respectively. Independent predictors of poorer outcome included age less than 2 years, relapse at transplantation, and second complete remission regardless of minimal residual disease status.

The models for each disease also predicted overall survival.

For AML, hazard ratios, ascending from good to very-high-risk tiers, were 1.00, 3.52, 4.67, and 8.62. For ALL risk tiers, ascending hazard ratios were 1.00, 2.16, and 3.86.

“In summary, the pediatric disease risk index validated for leukemia-free survival and overall survival successfully stratifies children with acute leukemia at the time of transplantation,” Dr. Qayed said.

She concluded her presentation by highlighting the practicality and relevance of the new scoring system.

“The components included in the scoring system used information that is readily available pretransplantation, lending support to the deliverability of the prognostic scoring system,” Dr. Qayed said. “It can further be used for improved interpretation of multicenter data and in clinical trials for risk stratification.”

In a virtual presentation, invited discussant Nirali N. Shah, MD, of the National Cancer Institute, Bethesda, Md., first emphasized the clinical importance of an accurate disease risk index for pediatric patients.

“When going into transplant, the No. 1 question that all parents will ask is: ‘Will my child be cured?’ ” she said.

According to Dr. Shah, the risk model developed by Dr. Qayed and colleagues is built on a strong foundation, including adequate sample size, comprehensive disease characterization, exclusion of patients that did not undergo myeloablative conditioning, and use of minimal residual disease status.

Still, more work is needed, Dr. Shah said.

“This DRI will need to be prospectively tested and compared to other established risk factors. For instance, minimal residual disease alone can be further stratified and has a significant role in establishing risk for posttransplant relapse. And the development of acute graft-versus-host disease also plays an important role in posttransplant relapse.”

Dr. Shah went on to outline potential areas of improvement.

“[F]uture directions for this study could include incorporation of early posttransplant events like graft-versus-host disease, potential stratification of the minimal residual disease results among those patients in complete remission, and potential application of this DRI to the adolescent and young adult population, which may have slight variation even from the adult DRI.”The study was funded by the National Institutes of Health. The investigators disclosed no conflicts of interest

SOURCE: Qayed M et al. ASCO 2020, Abstract 7503.

A treatment schedule of very attenuated chemotherapy using standard drugs is feasible and effective in frail and elderly patients with acute lymphoblastic leukemia (ALL), according to a prospective study published in Clinical Lymphoma, Myeloma & Leukemia.

VashiDonsk/Creative Commons/CC ASA 3.0

The study comprised 67 previously untreated patients with B- or T-lineage Philadelphia chromosome–negative ALL from 30 Spanish hospitals who were enrolled in the prospective, multicenter ALL-07FRAIL trial (NCT01358201) from the Spanish PETHEMA (Programa Español de Tratamientos en Hematologia) group from January 2008 to October 2019.

The median patient age in this analysis was 67 years and 51 patients (76%) were older than 70 years. The median Charlson Comorbidity Index was 5, with the main comorbidities being cardiovascular (47 patients), other neoplasia (24), diabetes (17), and very advanced age (>80 years; 12).

The attenuated treatment regimen consisted of a prephase with dexamethasone and intrathecal therapy with methotrexate was given for a maximum of 1 week. Then weekly induction therapy consisted of weekly vincristine (capped at 1 mg/week) and daily dexamethasone with a progressively decreasing dose along 4 weeks, as well as two additional doses of intrathecal methotrexate.

Those patients who achieved complete remission received maintenance therapy with mercaptopurine and methotrexate to complete 2 years of treatment. In addition, reinduction pulses with vincristine and dexamethasone were given every 3 months during the first year, according to Josep-Maria Ribera, MD, of the Universitat Autònoma de Barcelona, Badalona, Spain and colleagues on behalf of the PETHEMA group of the Spanish Society of Hematology.

The complete remission rate was 54% (36/67 patients). The median disease-free survival and overall survival were 6.9 months and 7.6 months, respectively.

Of the 32 patients who initiated maintenance therapy, 5 patients died of infection (2), hemorrhage (2), and acute cognitive impairment (1), and 23 relapsed, with a cumulative incidence of relapse of 74% and a median time to relapse of 12.3 months.

The most frequent toxic events reported were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases) followed by infections, metabolic (mainly hyperglycemia), and neurologic, according to the researchers.

“The lack of similar trials specifically directed to this frail population is one of the major strengths of this study, and we consider that this minimal chemotherapy approach could be used as a backbone for addition of immuno/targeted therapy in this subset of infirm patients,” the researchers concluded.

The study was supported by the CERCA Program/Generalitat de Catalunya and the Josep Carreras Leukemia Research Institute. The authors reported having no disclosures.

[email protected]

SOURCE: Ribera J-M et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 5. doi: 10.1016/j.clml.2020.03.011.

A treatment schedule of very attenuated chemotherapy using standard drugs is feasible and effective in frail and elderly patients with acute lymphoblastic leukemia (ALL), according to a prospective study published in Clinical Lymphoma, Myeloma & Leukemia.

VashiDonsk/Creative Commons/CC ASA 3.0

The study comprised 67 previously untreated patients with B- or T-lineage Philadelphia chromosome–negative ALL from 30 Spanish hospitals who were enrolled in the prospective, multicenter ALL-07FRAIL trial (NCT01358201) from the Spanish PETHEMA (Programa Español de Tratamientos en Hematologia) group from January 2008 to October 2019.

The median patient age in this analysis was 67 years and 51 patients (76%) were older than 70 years. The median Charlson Comorbidity Index was 5, with the main comorbidities being cardiovascular (47 patients), other neoplasia (24), diabetes (17), and very advanced age (>80 years; 12).

The attenuated treatment regimen consisted of a prephase with dexamethasone and intrathecal therapy with methotrexate was given for a maximum of 1 week. Then weekly induction therapy consisted of weekly vincristine (capped at 1 mg/week) and daily dexamethasone with a progressively decreasing dose along 4 weeks, as well as two additional doses of intrathecal methotrexate.

Those patients who achieved complete remission received maintenance therapy with mercaptopurine and methotrexate to complete 2 years of treatment. In addition, reinduction pulses with vincristine and dexamethasone were given every 3 months during the first year, according to Josep-Maria Ribera, MD, of the Universitat Autònoma de Barcelona, Badalona, Spain and colleagues on behalf of the PETHEMA group of the Spanish Society of Hematology.

The complete remission rate was 54% (36/67 patients). The median disease-free survival and overall survival were 6.9 months and 7.6 months, respectively.

Of the 32 patients who initiated maintenance therapy, 5 patients died of infection (2), hemorrhage (2), and acute cognitive impairment (1), and 23 relapsed, with a cumulative incidence of relapse of 74% and a median time to relapse of 12.3 months.

The most frequent toxic events reported were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases) followed by infections, metabolic (mainly hyperglycemia), and neurologic, according to the researchers.

“The lack of similar trials specifically directed to this frail population is one of the major strengths of this study, and we consider that this minimal chemotherapy approach could be used as a backbone for addition of immuno/targeted therapy in this subset of infirm patients,” the researchers concluded.

The study was supported by the CERCA Program/Generalitat de Catalunya and the Josep Carreras Leukemia Research Institute. The authors reported having no disclosures.

[email protected]

SOURCE: Ribera J-M et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 5. doi: 10.1016/j.clml.2020.03.011.

A treatment schedule of very attenuated chemotherapy using standard drugs is feasible and effective in frail and elderly patients with acute lymphoblastic leukemia (ALL), according to a prospective study published in Clinical Lymphoma, Myeloma & Leukemia.

VashiDonsk/Creative Commons/CC ASA 3.0

The study comprised 67 previously untreated patients with B- or T-lineage Philadelphia chromosome–negative ALL from 30 Spanish hospitals who were enrolled in the prospective, multicenter ALL-07FRAIL trial (NCT01358201) from the Spanish PETHEMA (Programa Español de Tratamientos en Hematologia) group from January 2008 to October 2019.

The median patient age in this analysis was 67 years and 51 patients (76%) were older than 70 years. The median Charlson Comorbidity Index was 5, with the main comorbidities being cardiovascular (47 patients), other neoplasia (24), diabetes (17), and very advanced age (>80 years; 12).

The attenuated treatment regimen consisted of a prephase with dexamethasone and intrathecal therapy with methotrexate was given for a maximum of 1 week. Then weekly induction therapy consisted of weekly vincristine (capped at 1 mg/week) and daily dexamethasone with a progressively decreasing dose along 4 weeks, as well as two additional doses of intrathecal methotrexate.

Those patients who achieved complete remission received maintenance therapy with mercaptopurine and methotrexate to complete 2 years of treatment. In addition, reinduction pulses with vincristine and dexamethasone were given every 3 months during the first year, according to Josep-Maria Ribera, MD, of the Universitat Autònoma de Barcelona, Badalona, Spain and colleagues on behalf of the PETHEMA group of the Spanish Society of Hematology.

The complete remission rate was 54% (36/67 patients). The median disease-free survival and overall survival were 6.9 months and 7.6 months, respectively.

Of the 32 patients who initiated maintenance therapy, 5 patients died of infection (2), hemorrhage (2), and acute cognitive impairment (1), and 23 relapsed, with a cumulative incidence of relapse of 74% and a median time to relapse of 12.3 months.

The most frequent toxic events reported were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases) followed by infections, metabolic (mainly hyperglycemia), and neurologic, according to the researchers.

“The lack of similar trials specifically directed to this frail population is one of the major strengths of this study, and we consider that this minimal chemotherapy approach could be used as a backbone for addition of immuno/targeted therapy in this subset of infirm patients,” the researchers concluded.

The study was supported by the CERCA Program/Generalitat de Catalunya and the Josep Carreras Leukemia Research Institute. The authors reported having no disclosures.

[email protected]

SOURCE: Ribera J-M et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 5. doi: 10.1016/j.clml.2020.03.011.

A universal chimeric antigen receptor (CAR) T-cell therapy produced responses in adults with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL), according to initial findings from an ongoing study.

The first five patients enrolled in this first-in-human study received conditioning and an infusion of the premanufactured CD7-targeted CAR T-cell therapy, TruUCAR GC027.

All five patients achieved a complete remission (CR) or CR with incomplete count recovery (CRi), although one patient had a morphological relapse at 1 month.

Xinxin Wang, PhD, reported these results at the AACR Virtual Meeting I. Dr. Wang is employed by Gracell Biotechnologies in Shanghai, China, which is the company developing TruUCAR GC027.

The CAR T-cell therapy is manufactured using lentivirus and leukopaks from HLA-mismatched healthy donors, according to Dr. Wang. TruUCAR GC027 contains second-generation CAR T cells with genomic disruption of TCR-alpha and CD7 to help prevent graft-versus-host disease and fratricide.

TruUCAR GC027 was previously shown to expand and have antileukemic activity in a murine model, Dr. Wang noted.
 

Patients and treatment

The five patients in the phase 1 study had a median age of 24 years (range, 19 to 38 years). They had heavily pretreated T-ALL, with a median of 5 prior lines of therapy (range, 1-9). Baseline bone marrow tumor burden ranged from 4% to 80.2% (median, 38.2%).

None of the patients received prior allogeneic hematopoietic stem cell transplant.

All patients received a preconditioning chemotherapy regimen. One patient received TruUCAR GC027 at dose level 1 (6 x 10⁶ cells/kg), three patients received dose level 2 (1 x 10⁷ cells/kg), and one patient received dose level 3 (1.5 x 10⁷ cells/kg) – each as a single infusion.
 

Expansion, response, and safety

“GC027 expansion, analyzed by flow [cytometry] was observed in most of the patients treated,” Dr. Wang said. “We started to see GC027 in the peripheral blood as early as day 5, with peaks around day 7-14.”

All five patients had a CR or CRi at the first postinfusion evaluation, which occurred at day 14 in four of the five patients. Four patients also achieved minimum residual disease (MRD) negativity by 1 month of follow-up and remained in MRD-negative CR at the February 6, 2020, data cutoff.

One patient achieved MRD-positive CR at day 14 but experienced morphological relapse at 1 month.

In the four patients with MRD-negative CR at 1 month, cellular expansion was observed as early as day 5 and continued for 2 weeks, but the patient who relapsed at day 29 showed no cellular expansion on flow cytometry, Dr. Wang said.

However, by a more sensitive quantitative polymerase chain reaction analysis, cellular expansion was observed in all five patients starting as early as day 1 after infusion, although the patient who relapsed had the shortest duration of expansion.

All patients developed cytokine release syndrome (CRS). Four patients experienced grade 3 CRS, and one experienced grade 4 CRS.

“The CRS was manageable and reversible,” Dr. Wang said, adding that none of the patients experienced neurotoxicity or graft-versus-host disease.

Prolonged cytopenia occurred in four patients, including one grade 1 case, two grade 3 cases, and one grade 4 case. Grade 3 pulmonary infections occurred in three patients, and grade 3 neutropenia occurred in all five patients.
 

‘Very impressive’ early results

Dr. Wang said the responses observed in this trial are notable because T-ALL constitutes 20%-25% of all adult ALL and 12%-15% of all pediatric ALL. T-ALL is highly aggressive, with event-free and overall survival of less than 25% in the relapsed setting. Dr. Wang noted that, despite the high unmet medical need and lack of treatment options for T-ALL, the development of novel immunotherapies has lagged.

One challenge is that T-ALL and normal T cells share common surface antigens, so targeted therapies for T-ALL will also target normal T cells. Another challenge is the potential contamination by malignant cells in autologous T-cell products, Dr. Wang said, noting that this can be avoided with universal CAR T cells.

Further, CD7 is a good target for T-ALL because it is expressed in more than 95% of T-ALL patients, she added.

“[TruUCAR GC027] demonstrated a very promising early response rate ... and showed a manageable toxicity profile at all three dose levels,” Dr. Wang said in closing, noting that further evaluation is warranted.

Indeed, the results of this next-generation CAR T-cell trial are “very impressive,” said invited discussant Yvonne Y. Chen, PhD, of the University of California, Los Angeles.

There have been concerns that “off-the-shelf” CAR T-cell products like TruUCAR GC027 might be limited by factors such as a reduced level of CAR T-cell persistence and therefore reduced efficacy leading to a need for repeat dosing, Dr. Chen noted. However, Dr. Wang and her colleagues showed a 100% CR/CRi rate with a single dose of CAR T cells and without graft-versus-host disease or neurotoxicity, Dr. Chen emphasized.

“I think it’s also important to note, however, that there’s quite a high incidence rate of grade 3 or higher toxicities, including CRS,” Dr. Chen said. “I suspect this may have something to do with the fairly high dosing levels used in this trial.”

The “big question,” however, is durability of the response, Dr. Chen said. “And this is something that the field will really watch as this trial progresses beyond the 7-month monitoring period ... reported today.”

Dr. Wang is an employee of Gracell Biotechnologies. Dr. Chen is cofounder of Kalthera Therapeutics and a scientific adviser for Gritstone Oncology and Notch Therapeutics.

[email protected]

SOURCE: Wang X et al. AACR 2020, Abstract CT052.

A universal chimeric antigen receptor (CAR) T-cell therapy produced responses in adults with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL), according to initial findings from an ongoing study.

The first five patients enrolled in this first-in-human study received conditioning and an infusion of the premanufactured CD7-targeted CAR T-cell therapy, TruUCAR GC027.

All five patients achieved a complete remission (CR) or CR with incomplete count recovery (CRi), although one patient had a morphological relapse at 1 month.

Xinxin Wang, PhD, reported these results at the AACR Virtual Meeting I. Dr. Wang is employed by Gracell Biotechnologies in Shanghai, China, which is the company developing TruUCAR GC027.

The CAR T-cell therapy is manufactured using lentivirus and leukopaks from HLA-mismatched healthy donors, according to Dr. Wang. TruUCAR GC027 contains second-generation CAR T cells with genomic disruption of TCR-alpha and CD7 to help prevent graft-versus-host disease and fratricide.

TruUCAR GC027 was previously shown to expand and have antileukemic activity in a murine model, Dr. Wang noted.
 

Patients and treatment

The five patients in the phase 1 study had a median age of 24 years (range, 19 to 38 years). They had heavily pretreated T-ALL, with a median of 5 prior lines of therapy (range, 1-9). Baseline bone marrow tumor burden ranged from 4% to 80.2% (median, 38.2%).

None of the patients received prior allogeneic hematopoietic stem cell transplant.

All patients received a preconditioning chemotherapy regimen. One patient received TruUCAR GC027 at dose level 1 (6 x 10⁶ cells/kg), three patients received dose level 2 (1 x 10⁷ cells/kg), and one patient received dose level 3 (1.5 x 10⁷ cells/kg) – each as a single infusion.
 

Expansion, response, and safety

“GC027 expansion, analyzed by flow [cytometry] was observed in most of the patients treated,” Dr. Wang said. “We started to see GC027 in the peripheral blood as early as day 5, with peaks around day 7-14.”

All five patients had a CR or CRi at the first postinfusion evaluation, which occurred at day 14 in four of the five patients. Four patients also achieved minimum residual disease (MRD) negativity by 1 month of follow-up and remained in MRD-negative CR at the February 6, 2020, data cutoff.

One patient achieved MRD-positive CR at day 14 but experienced morphological relapse at 1 month.

In the four patients with MRD-negative CR at 1 month, cellular expansion was observed as early as day 5 and continued for 2 weeks, but the patient who relapsed at day 29 showed no cellular expansion on flow cytometry, Dr. Wang said.

However, by a more sensitive quantitative polymerase chain reaction analysis, cellular expansion was observed in all five patients starting as early as day 1 after infusion, although the patient who relapsed had the shortest duration of expansion.

All patients developed cytokine release syndrome (CRS). Four patients experienced grade 3 CRS, and one experienced grade 4 CRS.

“The CRS was manageable and reversible,” Dr. Wang said, adding that none of the patients experienced neurotoxicity or graft-versus-host disease.

Prolonged cytopenia occurred in four patients, including one grade 1 case, two grade 3 cases, and one grade 4 case. Grade 3 pulmonary infections occurred in three patients, and grade 3 neutropenia occurred in all five patients.
 

‘Very impressive’ early results

Dr. Wang said the responses observed in this trial are notable because T-ALL constitutes 20%-25% of all adult ALL and 12%-15% of all pediatric ALL. T-ALL is highly aggressive, with event-free and overall survival of less than 25% in the relapsed setting. Dr. Wang noted that, despite the high unmet medical need and lack of treatment options for T-ALL, the development of novel immunotherapies has lagged.

One challenge is that T-ALL and normal T cells share common surface antigens, so targeted therapies for T-ALL will also target normal T cells. Another challenge is the potential contamination by malignant cells in autologous T-cell products, Dr. Wang said, noting that this can be avoided with universal CAR T cells.

Further, CD7 is a good target for T-ALL because it is expressed in more than 95% of T-ALL patients, she added.

“[TruUCAR GC027] demonstrated a very promising early response rate ... and showed a manageable toxicity profile at all three dose levels,” Dr. Wang said in closing, noting that further evaluation is warranted.

Indeed, the results of this next-generation CAR T-cell trial are “very impressive,” said invited discussant Yvonne Y. Chen, PhD, of the University of California, Los Angeles.

There have been concerns that “off-the-shelf” CAR T-cell products like TruUCAR GC027 might be limited by factors such as a reduced level of CAR T-cell persistence and therefore reduced efficacy leading to a need for repeat dosing, Dr. Chen noted. However, Dr. Wang and her colleagues showed a 100% CR/CRi rate with a single dose of CAR T cells and without graft-versus-host disease or neurotoxicity, Dr. Chen emphasized.

“I think it’s also important to note, however, that there’s quite a high incidence rate of grade 3 or higher toxicities, including CRS,” Dr. Chen said. “I suspect this may have something to do with the fairly high dosing levels used in this trial.”

The “big question,” however, is durability of the response, Dr. Chen said. “And this is something that the field will really watch as this trial progresses beyond the 7-month monitoring period ... reported today.”

Dr. Wang is an employee of Gracell Biotechnologies. Dr. Chen is cofounder of Kalthera Therapeutics and a scientific adviser for Gritstone Oncology and Notch Therapeutics.

[email protected]

SOURCE: Wang X et al. AACR 2020, Abstract CT052.

A universal chimeric antigen receptor (CAR) T-cell therapy produced responses in adults with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL), according to initial findings from an ongoing study.

The first five patients enrolled in this first-in-human study received conditioning and an infusion of the premanufactured CD7-targeted CAR T-cell therapy, TruUCAR GC027.

All five patients achieved a complete remission (CR) or CR with incomplete count recovery (CRi), although one patient had a morphological relapse at 1 month.

Xinxin Wang, PhD, reported these results at the AACR Virtual Meeting I. Dr. Wang is employed by Gracell Biotechnologies in Shanghai, China, which is the company developing TruUCAR GC027.

The CAR T-cell therapy is manufactured using lentivirus and leukopaks from HLA-mismatched healthy donors, according to Dr. Wang. TruUCAR GC027 contains second-generation CAR T cells with genomic disruption of TCR-alpha and CD7 to help prevent graft-versus-host disease and fratricide.

TruUCAR GC027 was previously shown to expand and have antileukemic activity in a murine model, Dr. Wang noted.
 

Patients and treatment

The five patients in the phase 1 study had a median age of 24 years (range, 19 to 38 years). They had heavily pretreated T-ALL, with a median of 5 prior lines of therapy (range, 1-9). Baseline bone marrow tumor burden ranged from 4% to 80.2% (median, 38.2%).

None of the patients received prior allogeneic hematopoietic stem cell transplant.

All patients received a preconditioning chemotherapy regimen. One patient received TruUCAR GC027 at dose level 1 (6 x 10⁶ cells/kg), three patients received dose level 2 (1 x 10⁷ cells/kg), and one patient received dose level 3 (1.5 x 10⁷ cells/kg) – each as a single infusion.
 

Expansion, response, and safety

“GC027 expansion, analyzed by flow [cytometry] was observed in most of the patients treated,” Dr. Wang said. “We started to see GC027 in the peripheral blood as early as day 5, with peaks around day 7-14.”

All five patients had a CR or CRi at the first postinfusion evaluation, which occurred at day 14 in four of the five patients. Four patients also achieved minimum residual disease (MRD) negativity by 1 month of follow-up and remained in MRD-negative CR at the February 6, 2020, data cutoff.

One patient achieved MRD-positive CR at day 14 but experienced morphological relapse at 1 month.

In the four patients with MRD-negative CR at 1 month, cellular expansion was observed as early as day 5 and continued for 2 weeks, but the patient who relapsed at day 29 showed no cellular expansion on flow cytometry, Dr. Wang said.

However, by a more sensitive quantitative polymerase chain reaction analysis, cellular expansion was observed in all five patients starting as early as day 1 after infusion, although the patient who relapsed had the shortest duration of expansion.

All patients developed cytokine release syndrome (CRS). Four patients experienced grade 3 CRS, and one experienced grade 4 CRS.

“The CRS was manageable and reversible,” Dr. Wang said, adding that none of the patients experienced neurotoxicity or graft-versus-host disease.

Prolonged cytopenia occurred in four patients, including one grade 1 case, two grade 3 cases, and one grade 4 case. Grade 3 pulmonary infections occurred in three patients, and grade 3 neutropenia occurred in all five patients.
 

‘Very impressive’ early results

Dr. Wang said the responses observed in this trial are notable because T-ALL constitutes 20%-25% of all adult ALL and 12%-15% of all pediatric ALL. T-ALL is highly aggressive, with event-free and overall survival of less than 25% in the relapsed setting. Dr. Wang noted that, despite the high unmet medical need and lack of treatment options for T-ALL, the development of novel immunotherapies has lagged.

One challenge is that T-ALL and normal T cells share common surface antigens, so targeted therapies for T-ALL will also target normal T cells. Another challenge is the potential contamination by malignant cells in autologous T-cell products, Dr. Wang said, noting that this can be avoided with universal CAR T cells.

Further, CD7 is a good target for T-ALL because it is expressed in more than 95% of T-ALL patients, she added.

“[TruUCAR GC027] demonstrated a very promising early response rate ... and showed a manageable toxicity profile at all three dose levels,” Dr. Wang said in closing, noting that further evaluation is warranted.

Indeed, the results of this next-generation CAR T-cell trial are “very impressive,” said invited discussant Yvonne Y. Chen, PhD, of the University of California, Los Angeles.

There have been concerns that “off-the-shelf” CAR T-cell products like TruUCAR GC027 might be limited by factors such as a reduced level of CAR T-cell persistence and therefore reduced efficacy leading to a need for repeat dosing, Dr. Chen noted. However, Dr. Wang and her colleagues showed a 100% CR/CRi rate with a single dose of CAR T cells and without graft-versus-host disease or neurotoxicity, Dr. Chen emphasized.

“I think it’s also important to note, however, that there’s quite a high incidence rate of grade 3 or higher toxicities, including CRS,” Dr. Chen said. “I suspect this may have something to do with the fairly high dosing levels used in this trial.”

The “big question,” however, is durability of the response, Dr. Chen said. “And this is something that the field will really watch as this trial progresses beyond the 7-month monitoring period ... reported today.”

Dr. Wang is an employee of Gracell Biotechnologies. Dr. Chen is cofounder of Kalthera Therapeutics and a scientific adviser for Gritstone Oncology and Notch Therapeutics.

[email protected]

SOURCE: Wang X et al. AACR 2020, Abstract CT052.

CD123, a membrane-bound interleukin-3 receptor, is overexpressed in many hematological malignancies, and it has been found useful in characterizing both acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL). CD123 expression also appears positively correlated with the presence of minimal residual disease (MRD) after treatment, and may be useful as a marker of treatment success, according to a report presented online in Clinical Lymphoma, Myeloma and Leukemia.

Nupur Das, MD, and colleagues from the Dr B.R. Ambedkar Institute Rotary Cancer Hospital, New Delhi, India, evaluated the pattern of CD123 expression across different subtypes of acute leukemia to assess its utility as a diagnostic marker, and to assess its impact on MRD assessment and early treatment outcome.

The evaluated the expression of CD123 in 757 samples of acute leukemia (479 treatment-naive and 278 follow-up samples) and compared the results with post-induction morphological remission (CR) and measurable residual disease (MRD) status.

The researchers used cut-offs of 5%, 10%, and 20% CD123-expression positive results to define a case as CD123 positive. On this basis, expression of CD123 was observed in 75.6%, 66.2%. and 50% of AML samples and 88.6%, 81.8%, and 75% of B-ALL samples respectively. They also found that none of the 12 T cell acute lymphoblastic leukemia (T-ALL) cases expressed CD123.

In addition, they found that CD123 expression was associated with MRD-positive status in both B-ALL (P < .001) and AML (P = .001).

“MRD is already an established post-treatment prognostication tool in acute leukemia and hence, the positive correlation of CD123 expression with MRD positivity in AML signifies its utility as an important marker to assess early response to therapy,” the researchers stated.

The authors reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Das N et al. Clin Lymphoma Myeloma Leuk. 2020 May 10; doi.org/10.1016/j.clml.2020.05.004.

CD123, a membrane-bound interleukin-3 receptor, is overexpressed in many hematological malignancies, and it has been found useful in characterizing both acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL). CD123 expression also appears positively correlated with the presence of minimal residual disease (MRD) after treatment, and may be useful as a marker of treatment success, according to a report presented online in Clinical Lymphoma, Myeloma and Leukemia.

Nupur Das, MD, and colleagues from the Dr B.R. Ambedkar Institute Rotary Cancer Hospital, New Delhi, India, evaluated the pattern of CD123 expression across different subtypes of acute leukemia to assess its utility as a diagnostic marker, and to assess its impact on MRD assessment and early treatment outcome.

The evaluated the expression of CD123 in 757 samples of acute leukemia (479 treatment-naive and 278 follow-up samples) and compared the results with post-induction morphological remission (CR) and measurable residual disease (MRD) status.

The researchers used cut-offs of 5%, 10%, and 20% CD123-expression positive results to define a case as CD123 positive. On this basis, expression of CD123 was observed in 75.6%, 66.2%. and 50% of AML samples and 88.6%, 81.8%, and 75% of B-ALL samples respectively. They also found that none of the 12 T cell acute lymphoblastic leukemia (T-ALL) cases expressed CD123.

In addition, they found that CD123 expression was associated with MRD-positive status in both B-ALL (P < .001) and AML (P = .001).

“MRD is already an established post-treatment prognostication tool in acute leukemia and hence, the positive correlation of CD123 expression with MRD positivity in AML signifies its utility as an important marker to assess early response to therapy,” the researchers stated.

The authors reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Das N et al. Clin Lymphoma Myeloma Leuk. 2020 May 10; doi.org/10.1016/j.clml.2020.05.004.

CD123, a membrane-bound interleukin-3 receptor, is overexpressed in many hematological malignancies, and it has been found useful in characterizing both acute myeloid leukemia (AML) and B-acute lymphoblastic leukemia (B-ALL). CD123 expression also appears positively correlated with the presence of minimal residual disease (MRD) after treatment, and may be useful as a marker of treatment success, according to a report presented online in Clinical Lymphoma, Myeloma and Leukemia.

Nupur Das, MD, and colleagues from the Dr B.R. Ambedkar Institute Rotary Cancer Hospital, New Delhi, India, evaluated the pattern of CD123 expression across different subtypes of acute leukemia to assess its utility as a diagnostic marker, and to assess its impact on MRD assessment and early treatment outcome.

The evaluated the expression of CD123 in 757 samples of acute leukemia (479 treatment-naive and 278 follow-up samples) and compared the results with post-induction morphological remission (CR) and measurable residual disease (MRD) status.

The researchers used cut-offs of 5%, 10%, and 20% CD123-expression positive results to define a case as CD123 positive. On this basis, expression of CD123 was observed in 75.6%, 66.2%. and 50% of AML samples and 88.6%, 81.8%, and 75% of B-ALL samples respectively. They also found that none of the 12 T cell acute lymphoblastic leukemia (T-ALL) cases expressed CD123.

In addition, they found that CD123 expression was associated with MRD-positive status in both B-ALL (P < .001) and AML (P = .001).

“MRD is already an established post-treatment prognostication tool in acute leukemia and hence, the positive correlation of CD123 expression with MRD positivity in AML signifies its utility as an important marker to assess early response to therapy,” the researchers stated.

The authors reported that they had no conflicts of interest.
 

[email protected]

SOURCE: Das N et al. Clin Lymphoma Myeloma Leuk. 2020 May 10; doi.org/10.1016/j.clml.2020.05.004.

The application of improved chemotherapy regimens and novel chemotherapy for acute lymphoblastic leukemia (ALL) has increased the complete remission rate to 85%-90%, however, secondary ALL is common, and the prolonged long-term survival rate is only 30%-50% among ALL patients.

Favorable outcomes decrease with increasing age, and overall survival is greater for adult patients with de novo ALL, compared with patients with secondary ALL, according to the Jiansheng Zhong of the department of hematology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China, and colleagues in a new study published online in Clinical Lymphoma, Myeloma & Leukemia.

The researchers retrospectively analyzed the results of 8,305 ALL patients undergoing chemotherapy from the Surveillance, Epidemiology, and End Results (SEER) database during 1975 to 2015, of which 7,454 (80.1%) cases were in the de novo ALL group, and 851 (19.9%) cases were in the secondary acute lymphoblastic leukemia (sALL) group. They used propensity matching before assessing overall survival between the two groups.

Demographically, the results showed that women ALL patients had a lower risk of death than men [hazard ratio (HR) = .93, P < .01], and that the mortality in blacks was higher than that of whites (HR = 1.29, P < .001).

For both ALL groups, patients aged 45-75 years and patients 75 years and older had a higher risk of death than younger patients (HR = 1.82, P < .001 and HR = 3.85, P < .001, respectively).

Although the mean age of de novo ALL group was significantly less than that of the sALL group (51.1 vs. 60.3 years, P < .001), after the propensity matching, the 1-, 2-, 3-, 4- and 5-year overall survival of the de novo ALL group was higher than that of the sALL group at all ages (18-75 years, P < .001).

The authors speculated that one reason for the across-the-board increased mortality in sALL, compared with de novo ALL, might be the fact that sALL patients have been reported to have more MLL gene rearrangements and chromosomal aberrations than are found in de novo ALL. This has previously been suggested as the reason for poor prognosis in secondary ALL patients.

One limitation of the study mentioned by the authors was the lack of individualized chemotherapy data available for analysis. “Considering that the features of sALL and chemotherapeutic modalities or therapy protocols may affect the mortality of sALL, more work is needed to be done in the future to demonstrate the association between chemotherapy and the prognosis of ALL patients, and the influence of cytogenetic lesions and molecular characteristics on sALL,” they concluded.

The authors declared they had no conflicts of interest.
 

[email protected]

SOURCE: Zhong J et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 30; doi.org/10.1016/j.clml.2020.04.013.

The application of improved chemotherapy regimens and novel chemotherapy for acute lymphoblastic leukemia (ALL) has increased the complete remission rate to 85%-90%, however, secondary ALL is common, and the prolonged long-term survival rate is only 30%-50% among ALL patients.

Favorable outcomes decrease with increasing age, and overall survival is greater for adult patients with de novo ALL, compared with patients with secondary ALL, according to the Jiansheng Zhong of the department of hematology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China, and colleagues in a new study published online in Clinical Lymphoma, Myeloma & Leukemia.

The researchers retrospectively analyzed the results of 8,305 ALL patients undergoing chemotherapy from the Surveillance, Epidemiology, and End Results (SEER) database during 1975 to 2015, of which 7,454 (80.1%) cases were in the de novo ALL group, and 851 (19.9%) cases were in the secondary acute lymphoblastic leukemia (sALL) group. They used propensity matching before assessing overall survival between the two groups.

Demographically, the results showed that women ALL patients had a lower risk of death than men [hazard ratio (HR) = .93, P < .01], and that the mortality in blacks was higher than that of whites (HR = 1.29, P < .001).

For both ALL groups, patients aged 45-75 years and patients 75 years and older had a higher risk of death than younger patients (HR = 1.82, P < .001 and HR = 3.85, P < .001, respectively).

Although the mean age of de novo ALL group was significantly less than that of the sALL group (51.1 vs. 60.3 years, P < .001), after the propensity matching, the 1-, 2-, 3-, 4- and 5-year overall survival of the de novo ALL group was higher than that of the sALL group at all ages (18-75 years, P < .001).

The authors speculated that one reason for the across-the-board increased mortality in sALL, compared with de novo ALL, might be the fact that sALL patients have been reported to have more MLL gene rearrangements and chromosomal aberrations than are found in de novo ALL. This has previously been suggested as the reason for poor prognosis in secondary ALL patients.

One limitation of the study mentioned by the authors was the lack of individualized chemotherapy data available for analysis. “Considering that the features of sALL and chemotherapeutic modalities or therapy protocols may affect the mortality of sALL, more work is needed to be done in the future to demonstrate the association between chemotherapy and the prognosis of ALL patients, and the influence of cytogenetic lesions and molecular characteristics on sALL,” they concluded.

The authors declared they had no conflicts of interest.
 

[email protected]

SOURCE: Zhong J et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 30; doi.org/10.1016/j.clml.2020.04.013.

The application of improved chemotherapy regimens and novel chemotherapy for acute lymphoblastic leukemia (ALL) has increased the complete remission rate to 85%-90%, however, secondary ALL is common, and the prolonged long-term survival rate is only 30%-50% among ALL patients.

Favorable outcomes decrease with increasing age, and overall survival is greater for adult patients with de novo ALL, compared with patients with secondary ALL, according to the Jiansheng Zhong of the department of hematology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, China, and colleagues in a new study published online in Clinical Lymphoma, Myeloma & Leukemia.

The researchers retrospectively analyzed the results of 8,305 ALL patients undergoing chemotherapy from the Surveillance, Epidemiology, and End Results (SEER) database during 1975 to 2015, of which 7,454 (80.1%) cases were in the de novo ALL group, and 851 (19.9%) cases were in the secondary acute lymphoblastic leukemia (sALL) group. They used propensity matching before assessing overall survival between the two groups.

Demographically, the results showed that women ALL patients had a lower risk of death than men [hazard ratio (HR) = .93, P < .01], and that the mortality in blacks was higher than that of whites (HR = 1.29, P < .001).

For both ALL groups, patients aged 45-75 years and patients 75 years and older had a higher risk of death than younger patients (HR = 1.82, P < .001 and HR = 3.85, P < .001, respectively).

Although the mean age of de novo ALL group was significantly less than that of the sALL group (51.1 vs. 60.3 years, P < .001), after the propensity matching, the 1-, 2-, 3-, 4- and 5-year overall survival of the de novo ALL group was higher than that of the sALL group at all ages (18-75 years, P < .001).

The authors speculated that one reason for the across-the-board increased mortality in sALL, compared with de novo ALL, might be the fact that sALL patients have been reported to have more MLL gene rearrangements and chromosomal aberrations than are found in de novo ALL. This has previously been suggested as the reason for poor prognosis in secondary ALL patients.

One limitation of the study mentioned by the authors was the lack of individualized chemotherapy data available for analysis. “Considering that the features of sALL and chemotherapeutic modalities or therapy protocols may affect the mortality of sALL, more work is needed to be done in the future to demonstrate the association between chemotherapy and the prognosis of ALL patients, and the influence of cytogenetic lesions and molecular characteristics on sALL,” they concluded.

The authors declared they had no conflicts of interest.
 

[email protected]

SOURCE: Zhong J et al. Clin Lymphoma Myeloma Leuk. 2020 Apr 30; doi.org/10.1016/j.clml.2020.04.013.

The SARS-CoV-2 pandemic poses significant risks to leukemia patients and their providers, impacting every aspect of care from diagnosis through therapy, according to an editorial letter published online in Leukemia Research.

VashiDonsk/Creative Commons/CC ASA 3.0

One key concern to be considered is the risk of missed or delayed diagnosis due to the pandemic conditions. An estimated 50%-75% of patients with acute leukemia are febrile at diagnosis and this puts them at high risk of a misdiagnosis of COVID-19 upon initial evaluation. As with other oncological conditions (primary mediastinal lymphoma or lung cancer, for example), which often present with a cough with or without fever, their symptoms “are likely to be considered trivial after a negative SARS-CoV-2 test,” with patients then being sent home without further assessment. In a rapidly progressing disease such as acute leukemia, this could lead to critical delays in therapeutic intervention.

The authors, from the Service and Central Laboratory of Hematology, Lausanne (Switzerland) University Hospital, also discussed the problems that might occur with regard to most standard forms of therapy. In particular, they addressed potential impacts of the pandemic on chemotherapy, bone marrow transplantation, maintenance treatments, supportive measures, and targeted therapies.

Of particular concern, “most patients may suffer from postponed chemotherapy, due to a shortage of isolation beds and blood products or the wish to avoid immunosuppressive treatments,” the authors noted, warning that “delay in chemotherapy initiation may negatively affect prognosis, [particularly in patients under age 60] with favorable- or intermediate-risk disease.”

With regard to stem cell transplantation, the authors detail the many potential difficulties with regard to procedures involving both donors and recipients, and warn that in some cases, delay in transplant could result in the reappearance of a significant minimal residual disease, which has a well-established negative impact on survival.

The authors also noted that blood product shortages have already begun in most affected countries, and how, in response, transfusion societies have called for conservative transfusion policies in strict adherence to evidence-based guidelines for patient’s blood management.

“COVID-19 will result in numerous casualties. Acute leukemia patients are at a higher risk of severe complications,” the authors stated. In particular, physicians should especially be aware of how treatment for acute leukemia may have “interactions with other drugs used to treat SARS-CoV-2–related infections/complications such as antibiotics, antiviral drugs, and various other drugs that prolong QTc or impact targeted-therapy pharmacokinetics,” they concluded.

The authors reported that they received no government or private funding for this research, and that they had no conflicts of interest.

[email protected]

SOURCE: Gavillet M et al. Leuk. Res. 2020. doi.org/10.1016/j.leukres.2020.106353.

The SARS-CoV-2 pandemic poses significant risks to leukemia patients and their providers, impacting every aspect of care from diagnosis through therapy, according to an editorial letter published online in Leukemia Research.

VashiDonsk/Creative Commons/CC ASA 3.0

One key concern to be considered is the risk of missed or delayed diagnosis due to the pandemic conditions. An estimated 50%-75% of patients with acute leukemia are febrile at diagnosis and this puts them at high risk of a misdiagnosis of COVID-19 upon initial evaluation. As with other oncological conditions (primary mediastinal lymphoma or lung cancer, for example), which often present with a cough with or without fever, their symptoms “are likely to be considered trivial after a negative SARS-CoV-2 test,” with patients then being sent home without further assessment. In a rapidly progressing disease such as acute leukemia, this could lead to critical delays in therapeutic intervention.

The authors, from the Service and Central Laboratory of Hematology, Lausanne (Switzerland) University Hospital, also discussed the problems that might occur with regard to most standard forms of therapy. In particular, they addressed potential impacts of the pandemic on chemotherapy, bone marrow transplantation, maintenance treatments, supportive measures, and targeted therapies.

Of particular concern, “most patients may suffer from postponed chemotherapy, due to a shortage of isolation beds and blood products or the wish to avoid immunosuppressive treatments,” the authors noted, warning that “delay in chemotherapy initiation may negatively affect prognosis, [particularly in patients under age 60] with favorable- or intermediate-risk disease.”

With regard to stem cell transplantation, the authors detail the many potential difficulties with regard to procedures involving both donors and recipients, and warn that in some cases, delay in transplant could result in the reappearance of a significant minimal residual disease, which has a well-established negative impact on survival.

The authors also noted that blood product shortages have already begun in most affected countries, and how, in response, transfusion societies have called for conservative transfusion policies in strict adherence to evidence-based guidelines for patient’s blood management.

“COVID-19 will result in numerous casualties. Acute leukemia patients are at a higher risk of severe complications,” the authors stated. In particular, physicians should especially be aware of how treatment for acute leukemia may have “interactions with other drugs used to treat SARS-CoV-2–related infections/complications such as antibiotics, antiviral drugs, and various other drugs that prolong QTc or impact targeted-therapy pharmacokinetics,” they concluded.

The authors reported that they received no government or private funding for this research, and that they had no conflicts of interest.

[email protected]

SOURCE: Gavillet M et al. Leuk. Res. 2020. doi.org/10.1016/j.leukres.2020.106353.

The SARS-CoV-2 pandemic poses significant risks to leukemia patients and their providers, impacting every aspect of care from diagnosis through therapy, according to an editorial letter published online in Leukemia Research.

VashiDonsk/Creative Commons/CC ASA 3.0

One key concern to be considered is the risk of missed or delayed diagnosis due to the pandemic conditions. An estimated 50%-75% of patients with acute leukemia are febrile at diagnosis and this puts them at high risk of a misdiagnosis of COVID-19 upon initial evaluation. As with other oncological conditions (primary mediastinal lymphoma or lung cancer, for example), which often present with a cough with or without fever, their symptoms “are likely to be considered trivial after a negative SARS-CoV-2 test,” with patients then being sent home without further assessment. In a rapidly progressing disease such as acute leukemia, this could lead to critical delays in therapeutic intervention.

The authors, from the Service and Central Laboratory of Hematology, Lausanne (Switzerland) University Hospital, also discussed the problems that might occur with regard to most standard forms of therapy. In particular, they addressed potential impacts of the pandemic on chemotherapy, bone marrow transplantation, maintenance treatments, supportive measures, and targeted therapies.

Of particular concern, “most patients may suffer from postponed chemotherapy, due to a shortage of isolation beds and blood products or the wish to avoid immunosuppressive treatments,” the authors noted, warning that “delay in chemotherapy initiation may negatively affect prognosis, [particularly in patients under age 60] with favorable- or intermediate-risk disease.”

With regard to stem cell transplantation, the authors detail the many potential difficulties with regard to procedures involving both donors and recipients, and warn that in some cases, delay in transplant could result in the reappearance of a significant minimal residual disease, which has a well-established negative impact on survival.

The authors also noted that blood product shortages have already begun in most affected countries, and how, in response, transfusion societies have called for conservative transfusion policies in strict adherence to evidence-based guidelines for patient’s blood management.

“COVID-19 will result in numerous casualties. Acute leukemia patients are at a higher risk of severe complications,” the authors stated. In particular, physicians should especially be aware of how treatment for acute leukemia may have “interactions with other drugs used to treat SARS-CoV-2–related infections/complications such as antibiotics, antiviral drugs, and various other drugs that prolong QTc or impact targeted-therapy pharmacokinetics,” they concluded.

The authors reported that they received no government or private funding for this research, and that they had no conflicts of interest.

[email protected]

SOURCE: Gavillet M et al. Leuk. Res. 2020. doi.org/10.1016/j.leukres.2020.106353.

ORLANDO – A second hematopoietic stem cell transplant can be a successful salvage therapy for a child who has experienced a relapse following a first allogeneic transplant, investigators report.

Neil Osterweil/MDedge News

A retrospective study of 221 children who experienced a relapse after a first hematopoietic stem cell transplant (HSCT) showed that 3-year overall survival (OS) was six times higher among those who had second HSCT, compared with those who did not, reported Akshay Sharma, MBBS, from St. Jude’s Children’s Research Hospital in Memphis.

“We found that factors that are typically associated with poor outcomes after transplant such as disease status at the time of first transplantation – being in remission or not, type of transplant – myeloablative or reduced intensity, and choice of donor were generally not significantly predictive of outcomes following posttransplant relapse in our multivariable model,” he said at the Transplantation and Cellular Therapy Meetings.

Relapse is the most common cause of death after HSCT, and 20%-30% of children who undergo allogeneic HSCT will experience a relapse.

To study this issue, Dr. Sharma and colleagues took a retrospective look at 703 patients 21 and younger who received a first alloHSCT at St. Jude’s for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome from 1990 through 2018. Of this cohort, 211 patients (31%) experienced a relapse after transplant.

There were no significant differences between patients who had a relapse and those who did not in sex, race, conditioning-regimen intensity, performance status, donor type, or graft type (peripheral blood stem cell, umbilical cord blood, bone marrow), or in the incidence of acute graft-versus-host disease GVHD.

The investigators found that, as expected, outcomes were poor for patients who experienced a posttransplant relapse, with 3-year overall survival from relapse for the 221 patients of just 10%.

In multivariable analysis controlling for sex, disease status at the time of first transplant, interval from first transplant to relapse, management after relapse, chronic GVHD and year of relapse, factors significantly associated with worse overall survival were relapse within 6 months of transplant vs. later than 6 months (hazard ratio, 4.6; P < .001) and decade of transplant (HR, 2.6 for 1990-2000 and 1.6 for 2001-2010 vs. 2011-2018; P < .001).

In contrast, both second HSCT and donor lymphocyte infusion were associated with better overall survival, compared with postrelapse chemotherapy or supportive care (HR, 0.04 and 0.6, respectively; P < .001 for both comparisons).

A longer interval from first transplant to relapse was the strongest predictor of long-term survival, Dr. Sharma said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Among the 221 patients who had a relapse, 61 (28%) had a second HSCT, 28 (13%) received only donor lymphocyte infusions, without second transplant, and 132 (62%) received either chemotherapy or supportive care.

The 3-year overall survival rate for patients who received a second transplant was 28%, compared with 4% for those who did not have a repeat HSCT. The most important independent predictors for getting a second transplant were longer time to relapse after first transplant, first transplantation from a matched sibling donor instead of from a haploidentical donor, some degree of acute GVHD, and decade of first transplant (current decade vs. earlier decades).

The investigators also looked at guideline recommendations from both the American Society of Hematology and UK National Health Service regarding second allogenenic transplant after relapse.

ASH guidelines say that “patients with chemo-sensitive disease in remission who had a long initial remission (> 6-12 months) after first transplant and who never developed any GVHD” are most likely to benefit from a second transplant.

NHS guidelines say that a second transplant can be considered for patients who experience relapse more than 12 months after first alloHSCT. But as Dr. Sharma and colleagues discovered, patients who had a second transplant had better overall survival regardless of time from first to second transplant, compared with patients who had later relapses but no second transplant.

“With these data in mind, we submit that these ASH and NHS guidelines, which are based on older data from the 1900s and 2000 and are mostly based on adult data and do not include much pediatric data should be reconsidered, at least in the context of pediatric patients as we approach them,” he said.

Jaap-Jan Boelens, MD, PhD, a pediatric transplant specialist at Memorial Sloan Kettering Cancer Center in New York City, who was not involved in the study, said that the use of second transplant as salvage therapy is becoming more common at his center.

“But there is a little nuance,” he said in an interview. “If someone relapses a month after transplant, let’s say, it doesn’t make sense to go for another allo transplant. But if the interval between transplant is longer, more than half a year, we usually consider going for a second allo transplant.”

The decision to attempt a second transplant may also hinge on the disease the patient is being treated for, and on the depth of remission prior to relapse, he said.

Reggie E. Duerst, MD, director of the Stem Cell Transplant Program at Ann & Robert H. Lurie Children’s Hospital of Chicago, said that trying to replicate the conditions of the first transplant may not work.

“It’s also a function of who was the donor for the first transplant – was it a matched sibling? And then for the second one do you go to an unrelated donor, or a half-matched relative, banking on the fact that the donor’s immune system for the second transplant is going to be able to mediate some kind of graft-versus-leukemia effect that wasn’t there the first time around?” he said.

Dr. Duerst, who was not involved in the study, noted that, for some patients with lymphoid malignancies, chimeric antigen receptor (CAR) T-cell therapy may be a more effective salvage strategy than second transplant, but added that it’s still too soon to know which strategy will be more effective.

The study was supported by St. Jude’s, the American Society of Hematology, and the American Society for Transplantation and Cellular Therapy. Dr. Sharma, Dr. Boelens, and Dr. Duerst reported having no relevant disclosures.

SOURCE: Sharma A et al. TCT 2020, Abstract 116.

ORLANDO – A second hematopoietic stem cell transplant can be a successful salvage therapy for a child who has experienced a relapse following a first allogeneic transplant, investigators report.

Neil Osterweil/MDedge News

A retrospective study of 221 children who experienced a relapse after a first hematopoietic stem cell transplant (HSCT) showed that 3-year overall survival (OS) was six times higher among those who had second HSCT, compared with those who did not, reported Akshay Sharma, MBBS, from St. Jude’s Children’s Research Hospital in Memphis.

“We found that factors that are typically associated with poor outcomes after transplant such as disease status at the time of first transplantation – being in remission or not, type of transplant – myeloablative or reduced intensity, and choice of donor were generally not significantly predictive of outcomes following posttransplant relapse in our multivariable model,” he said at the Transplantation and Cellular Therapy Meetings.

Relapse is the most common cause of death after HSCT, and 20%-30% of children who undergo allogeneic HSCT will experience a relapse.

To study this issue, Dr. Sharma and colleagues took a retrospective look at 703 patients 21 and younger who received a first alloHSCT at St. Jude’s for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome from 1990 through 2018. Of this cohort, 211 patients (31%) experienced a relapse after transplant.

There were no significant differences between patients who had a relapse and those who did not in sex, race, conditioning-regimen intensity, performance status, donor type, or graft type (peripheral blood stem cell, umbilical cord blood, bone marrow), or in the incidence of acute graft-versus-host disease GVHD.

The investigators found that, as expected, outcomes were poor for patients who experienced a posttransplant relapse, with 3-year overall survival from relapse for the 221 patients of just 10%.

In multivariable analysis controlling for sex, disease status at the time of first transplant, interval from first transplant to relapse, management after relapse, chronic GVHD and year of relapse, factors significantly associated with worse overall survival were relapse within 6 months of transplant vs. later than 6 months (hazard ratio, 4.6; P < .001) and decade of transplant (HR, 2.6 for 1990-2000 and 1.6 for 2001-2010 vs. 2011-2018; P < .001).

In contrast, both second HSCT and donor lymphocyte infusion were associated with better overall survival, compared with postrelapse chemotherapy or supportive care (HR, 0.04 and 0.6, respectively; P < .001 for both comparisons).

A longer interval from first transplant to relapse was the strongest predictor of long-term survival, Dr. Sharma said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Among the 221 patients who had a relapse, 61 (28%) had a second HSCT, 28 (13%) received only donor lymphocyte infusions, without second transplant, and 132 (62%) received either chemotherapy or supportive care.

The 3-year overall survival rate for patients who received a second transplant was 28%, compared with 4% for those who did not have a repeat HSCT. The most important independent predictors for getting a second transplant were longer time to relapse after first transplant, first transplantation from a matched sibling donor instead of from a haploidentical donor, some degree of acute GVHD, and decade of first transplant (current decade vs. earlier decades).

The investigators also looked at guideline recommendations from both the American Society of Hematology and UK National Health Service regarding second allogenenic transplant after relapse.

ASH guidelines say that “patients with chemo-sensitive disease in remission who had a long initial remission (> 6-12 months) after first transplant and who never developed any GVHD” are most likely to benefit from a second transplant.

NHS guidelines say that a second transplant can be considered for patients who experience relapse more than 12 months after first alloHSCT. But as Dr. Sharma and colleagues discovered, patients who had a second transplant had better overall survival regardless of time from first to second transplant, compared with patients who had later relapses but no second transplant.

“With these data in mind, we submit that these ASH and NHS guidelines, which are based on older data from the 1900s and 2000 and are mostly based on adult data and do not include much pediatric data should be reconsidered, at least in the context of pediatric patients as we approach them,” he said.

Jaap-Jan Boelens, MD, PhD, a pediatric transplant specialist at Memorial Sloan Kettering Cancer Center in New York City, who was not involved in the study, said that the use of second transplant as salvage therapy is becoming more common at his center.

“But there is a little nuance,” he said in an interview. “If someone relapses a month after transplant, let’s say, it doesn’t make sense to go for another allo transplant. But if the interval between transplant is longer, more than half a year, we usually consider going for a second allo transplant.”

The decision to attempt a second transplant may also hinge on the disease the patient is being treated for, and on the depth of remission prior to relapse, he said.

Reggie E. Duerst, MD, director of the Stem Cell Transplant Program at Ann & Robert H. Lurie Children’s Hospital of Chicago, said that trying to replicate the conditions of the first transplant may not work.

“It’s also a function of who was the donor for the first transplant – was it a matched sibling? And then for the second one do you go to an unrelated donor, or a half-matched relative, banking on the fact that the donor’s immune system for the second transplant is going to be able to mediate some kind of graft-versus-leukemia effect that wasn’t there the first time around?” he said.

Dr. Duerst, who was not involved in the study, noted that, for some patients with lymphoid malignancies, chimeric antigen receptor (CAR) T-cell therapy may be a more effective salvage strategy than second transplant, but added that it’s still too soon to know which strategy will be more effective.

The study was supported by St. Jude’s, the American Society of Hematology, and the American Society for Transplantation and Cellular Therapy. Dr. Sharma, Dr. Boelens, and Dr. Duerst reported having no relevant disclosures.

SOURCE: Sharma A et al. TCT 2020, Abstract 116.

ORLANDO – A second hematopoietic stem cell transplant can be a successful salvage therapy for a child who has experienced a relapse following a first allogeneic transplant, investigators report.

Neil Osterweil/MDedge News

A retrospective study of 221 children who experienced a relapse after a first hematopoietic stem cell transplant (HSCT) showed that 3-year overall survival (OS) was six times higher among those who had second HSCT, compared with those who did not, reported Akshay Sharma, MBBS, from St. Jude’s Children’s Research Hospital in Memphis.

“We found that factors that are typically associated with poor outcomes after transplant such as disease status at the time of first transplantation – being in remission or not, type of transplant – myeloablative or reduced intensity, and choice of donor were generally not significantly predictive of outcomes following posttransplant relapse in our multivariable model,” he said at the Transplantation and Cellular Therapy Meetings.

Relapse is the most common cause of death after HSCT, and 20%-30% of children who undergo allogeneic HSCT will experience a relapse.

To study this issue, Dr. Sharma and colleagues took a retrospective look at 703 patients 21 and younger who received a first alloHSCT at St. Jude’s for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome from 1990 through 2018. Of this cohort, 211 patients (31%) experienced a relapse after transplant.

There were no significant differences between patients who had a relapse and those who did not in sex, race, conditioning-regimen intensity, performance status, donor type, or graft type (peripheral blood stem cell, umbilical cord blood, bone marrow), or in the incidence of acute graft-versus-host disease GVHD.

The investigators found that, as expected, outcomes were poor for patients who experienced a posttransplant relapse, with 3-year overall survival from relapse for the 221 patients of just 10%.

In multivariable analysis controlling for sex, disease status at the time of first transplant, interval from first transplant to relapse, management after relapse, chronic GVHD and year of relapse, factors significantly associated with worse overall survival were relapse within 6 months of transplant vs. later than 6 months (hazard ratio, 4.6; P < .001) and decade of transplant (HR, 2.6 for 1990-2000 and 1.6 for 2001-2010 vs. 2011-2018; P < .001).

In contrast, both second HSCT and donor lymphocyte infusion were associated with better overall survival, compared with postrelapse chemotherapy or supportive care (HR, 0.04 and 0.6, respectively; P < .001 for both comparisons).

A longer interval from first transplant to relapse was the strongest predictor of long-term survival, Dr. Sharma said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.

Among the 221 patients who had a relapse, 61 (28%) had a second HSCT, 28 (13%) received only donor lymphocyte infusions, without second transplant, and 132 (62%) received either chemotherapy or supportive care.

The 3-year overall survival rate for patients who received a second transplant was 28%, compared with 4% for those who did not have a repeat HSCT. The most important independent predictors for getting a second transplant were longer time to relapse after first transplant, first transplantation from a matched sibling donor instead of from a haploidentical donor, some degree of acute GVHD, and decade of first transplant (current decade vs. earlier decades).

The investigators also looked at guideline recommendations from both the American Society of Hematology and UK National Health Service regarding second allogenenic transplant after relapse.

ASH guidelines say that “patients with chemo-sensitive disease in remission who had a long initial remission (> 6-12 months) after first transplant and who never developed any GVHD” are most likely to benefit from a second transplant.

NHS guidelines say that a second transplant can be considered for patients who experience relapse more than 12 months after first alloHSCT. But as Dr. Sharma and colleagues discovered, patients who had a second transplant had better overall survival regardless of time from first to second transplant, compared with patients who had later relapses but no second transplant.

“With these data in mind, we submit that these ASH and NHS guidelines, which are based on older data from the 1900s and 2000 and are mostly based on adult data and do not include much pediatric data should be reconsidered, at least in the context of pediatric patients as we approach them,” he said.

Jaap-Jan Boelens, MD, PhD, a pediatric transplant specialist at Memorial Sloan Kettering Cancer Center in New York City, who was not involved in the study, said that the use of second transplant as salvage therapy is becoming more common at his center.

“But there is a little nuance,” he said in an interview. “If someone relapses a month after transplant, let’s say, it doesn’t make sense to go for another allo transplant. But if the interval between transplant is longer, more than half a year, we usually consider going for a second allo transplant.”

The decision to attempt a second transplant may also hinge on the disease the patient is being treated for, and on the depth of remission prior to relapse, he said.

Reggie E. Duerst, MD, director of the Stem Cell Transplant Program at Ann & Robert H. Lurie Children’s Hospital of Chicago, said that trying to replicate the conditions of the first transplant may not work.

“It’s also a function of who was the donor for the first transplant – was it a matched sibling? And then for the second one do you go to an unrelated donor, or a half-matched relative, banking on the fact that the donor’s immune system for the second transplant is going to be able to mediate some kind of graft-versus-leukemia effect that wasn’t there the first time around?” he said.

Dr. Duerst, who was not involved in the study, noted that, for some patients with lymphoid malignancies, chimeric antigen receptor (CAR) T-cell therapy may be a more effective salvage strategy than second transplant, but added that it’s still too soon to know which strategy will be more effective.

The study was supported by St. Jude’s, the American Society of Hematology, and the American Society for Transplantation and Cellular Therapy. Dr. Sharma, Dr. Boelens, and Dr. Duerst reported having no relevant disclosures.

SOURCE: Sharma A et al. TCT 2020, Abstract 116.

The International Association for the Study of Lung Cancer (IASLC) is naming the Translational Research Lectureship Award after Fred R. Hirsch, MD, PhD, of the Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

Dr. Hirsch was a longtime member of the IASLC and served as chief executive officer of the association from 2013 through October 2018. During this time, Dr. Hirsch grew the IASLC staff from 5 to 23 people and doubled the organization’s membership. The IASLC World Conference on Lung Cancer became an annual meeting under Dr. Hirsch’s direction and reported record attendance, according to their website.

The recipient of the Fred R. Hirsch Lectureship Award for Translational Research will be recognized at the IASLC 2020 World Conference on Lung Cancer, which is set to take place in Singapore on August 9-12, 2020.

In other news, the American Cancer Society (ACS) announced that it has awarded the 2020 Medal of Honor to three researchers. The recipients will be recognized at a black-tie ceremony in New York on Nov. 11, 2020.

Lewis C. Cantley, PhD, of Weill Cornell Medicine, New York, won the Medal of Honor for Basic Research. This award honors researchers whose work will have a “lasting impact on the cancer field” or who have made important discoveries or inventions within the field, according to the ACS.

Dr. Cantley won the award for research that has improved our understanding of cancer metabolism. He is known for his contributions to the discovery and study of phosphoinositide 3-kinase, which plays a role in many cancers and has become a target for therapies.

Leslie Bernstein, PhD, of City of Hope National Medical Center in Duarte, Calif., has won the Medal of Honor in Cancer Control. This award honors individuals who have made strides in public health, public communication, or public policy that have had an impact on cancer control.

Dr. Bernstein won the award for her work linking physical activity to a reduced risk of breast cancer. She is currently investigating links between hormone exposures, physical activity, obesity, and cancer, as well as examining how breast cancer impacts patients’ lives after treatment.

Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., has won the Medal of Honor in Clinical Research. This award honors researchers whose work has significantly improved cancer patients’ outcomes.

Dr. Pui won the award for his work in childhood acute lymphoblastic leukemia. Dr. Pui’s work has led to increased global treatment access, improved survival rates, and better quality of life for patients with childhood acute lymphoblastic leukemia.

[email protected]

The International Association for the Study of Lung Cancer (IASLC) is naming the Translational Research Lectureship Award after Fred R. Hirsch, MD, PhD, of the Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

Dr. Hirsch was a longtime member of the IASLC and served as chief executive officer of the association from 2013 through October 2018. During this time, Dr. Hirsch grew the IASLC staff from 5 to 23 people and doubled the organization’s membership. The IASLC World Conference on Lung Cancer became an annual meeting under Dr. Hirsch’s direction and reported record attendance, according to their website.

The recipient of the Fred R. Hirsch Lectureship Award for Translational Research will be recognized at the IASLC 2020 World Conference on Lung Cancer, which is set to take place in Singapore on August 9-12, 2020.

In other news, the American Cancer Society (ACS) announced that it has awarded the 2020 Medal of Honor to three researchers. The recipients will be recognized at a black-tie ceremony in New York on Nov. 11, 2020.

Lewis C. Cantley, PhD, of Weill Cornell Medicine, New York, won the Medal of Honor for Basic Research. This award honors researchers whose work will have a “lasting impact on the cancer field” or who have made important discoveries or inventions within the field, according to the ACS.

Dr. Cantley won the award for research that has improved our understanding of cancer metabolism. He is known for his contributions to the discovery and study of phosphoinositide 3-kinase, which plays a role in many cancers and has become a target for therapies.

Leslie Bernstein, PhD, of City of Hope National Medical Center in Duarte, Calif., has won the Medal of Honor in Cancer Control. This award honors individuals who have made strides in public health, public communication, or public policy that have had an impact on cancer control.

Dr. Bernstein won the award for her work linking physical activity to a reduced risk of breast cancer. She is currently investigating links between hormone exposures, physical activity, obesity, and cancer, as well as examining how breast cancer impacts patients’ lives after treatment.

Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., has won the Medal of Honor in Clinical Research. This award honors researchers whose work has significantly improved cancer patients’ outcomes.

Dr. Pui won the award for his work in childhood acute lymphoblastic leukemia. Dr. Pui’s work has led to increased global treatment access, improved survival rates, and better quality of life for patients with childhood acute lymphoblastic leukemia.

[email protected]

The International Association for the Study of Lung Cancer (IASLC) is naming the Translational Research Lectureship Award after Fred R. Hirsch, MD, PhD, of the Tisch Cancer Institute and Icahn School of Medicine at Mount Sinai, New York.

Dr. Hirsch was a longtime member of the IASLC and served as chief executive officer of the association from 2013 through October 2018. During this time, Dr. Hirsch grew the IASLC staff from 5 to 23 people and doubled the organization’s membership. The IASLC World Conference on Lung Cancer became an annual meeting under Dr. Hirsch’s direction and reported record attendance, according to their website.

The recipient of the Fred R. Hirsch Lectureship Award for Translational Research will be recognized at the IASLC 2020 World Conference on Lung Cancer, which is set to take place in Singapore on August 9-12, 2020.

In other news, the American Cancer Society (ACS) announced that it has awarded the 2020 Medal of Honor to three researchers. The recipients will be recognized at a black-tie ceremony in New York on Nov. 11, 2020.

Lewis C. Cantley, PhD, of Weill Cornell Medicine, New York, won the Medal of Honor for Basic Research. This award honors researchers whose work will have a “lasting impact on the cancer field” or who have made important discoveries or inventions within the field, according to the ACS.

Dr. Cantley won the award for research that has improved our understanding of cancer metabolism. He is known for his contributions to the discovery and study of phosphoinositide 3-kinase, which plays a role in many cancers and has become a target for therapies.

Leslie Bernstein, PhD, of City of Hope National Medical Center in Duarte, Calif., has won the Medal of Honor in Cancer Control. This award honors individuals who have made strides in public health, public communication, or public policy that have had an impact on cancer control.

Dr. Bernstein won the award for her work linking physical activity to a reduced risk of breast cancer. She is currently investigating links between hormone exposures, physical activity, obesity, and cancer, as well as examining how breast cancer impacts patients’ lives after treatment.

Ching-Hon Pui, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., has won the Medal of Honor in Clinical Research. This award honors researchers whose work has significantly improved cancer patients’ outcomes.

Dr. Pui won the award for his work in childhood acute lymphoblastic leukemia. Dr. Pui’s work has led to increased global treatment access, improved survival rates, and better quality of life for patients with childhood acute lymphoblastic leukemia.

[email protected]

ORLANDO – Inotuzumab ozogamicin (InO), a CD22-targeted antibody approved for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), showed promising safety and efficacy in children and young adults with R/R B-ALL in a phase 2 trial.

Of 48 patients aged 1-21 years enrolled in the Children’s Oncology Group (COG) Protocol AALL1621 and evaluable for response and toxicity after treatment with the approved adult InO dose, 19 achieved a complete response (CR) and 9 achieved a complete response with incomplete count recovery (CRi) after the first treatment cycle, for an overall CR/CRi rate of 58.3%, Maureen M. O’Brien, MD, reported at the annual meeting of the American Society of Hematology.

Of those with CR/CRi, 19 (65.5%) achieved minimal residual disease less than 0.01%, said Dr. O’Brien, a pediatric hematologist and medical director of the Leukemia/Lymphoma Program at the Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center.

Three patients had a partial response (PR), nine had stable disease (SD), and eight had progressive disease (PD), and one of each with PR and SD achieved CR/CRi after a second treatment cycle.

“Of note, two patients who were characterized as [having] progressive disease actually had marrow complete response with incomplete count recovery, but had progressive CNS disease,” she said.

Patients included in the single-arm trial had CD22-positive B-ALL, defined as B-ALL with greater than 20% of blasts expressing CD22, and were in at least their second relapse, were refractory to two prior induction regimens, or had a relapse after hematopoietic stem cell transplantation (HSCT). One exception was that patients with Down syndrome were allowed inclusion after a first relapse, she noted.

Median patient age was 9 years, four patients had CNS 3 status, three had Down syndrome, and most were heavily pretreated, with 32 in at least their second relapse.

“Most patients had significant marrow disease burden, with a median marrow blast percentage of 81%,” Dr. O’Brien said. “In terms of prior therapy, 23% had prior transplant, 23% had prior CD19 [chimeric antigen receptor (CAR)] T-cell therapy – including two patients with prior CD22 CAR T, and 29% of patients had received prior blinatumomab.”

All patients received one cycle of InO at a dose of 1.8mg/m², with .8mg/m² given on day 1 and 0.5mg/m2 given on days 8 and 15. Intrathecal therapy was determined based on CNS status.

Patients with at least stable disease at day 28 were eligible for a second cycle; those with CR or CRi received InO at a dose of 0.5 mg/m² on days 1, 8, and 15 in cycle 2, and those without CR/CRi received the same fractionated dose as in cycle 1. Patients with CR/CRi after two cycles were eligible for up to six total cycles at investigator discretion, Dr. O’Brien explained, adding that 26 of 40 patients eligible for cycle 2 proceeded, including 13 of 18 with MRD less than .01%, 6 of 10 with MRD of 0.01% or greater, and 7 of 12 with PR/SD.

After cycle 2, all 13 with MRD less than .01% maintained that MRD level, 3 of 6 with MRD of .01% or greater achieved MRD less than .01%, 2 of 7 with PR/SD achieved CRi with MRD of .01% or greater – and one of those 2 was MRD negative after a third cycle.

Seven patients received three or more cycles.

“Therapy was extremely well tolerated,” Dr. O’Brien said, noting that the most common nonhematological grade 3 or higher adverse events occurring in at least 5% of patients in cycle 1 were febrile neutropenia and infection, occurring in 27.1% and 16.7% of patients, respectively. “But toxicity was quite minimal.”

Hepatic toxicity included four cases of grade 3 alanine transaminase and one grade 3 bilirubin toxicity in cycle 1, and one grade 3 ALT in cycle 2.

“Importantly, there were no inotuzumab dose modifications or delays due to hepatic toxicity,” she said.

Nine patients experienced 11 dose-limiting toxicities in cycle 1, including 7 involving prolonged count recovery beyond day 42, which was not attributable to disease, and 4 nonhematologic events, including drug reaction with eosinophilia and systemic symptoms, bronchopulmonary hemorrhage, respiratory distress, and a postintrathecal methotrexate stroke.

Sinusoidal obstruction syndrome (SOS) developed in 5 of the 48 patients, all in patients who underwent transplant after InO treatment. Only one of the five had undergone a prior transplant. All SOS cases were grade 3 and were treated with defibrotide; four cases resolved quickly, and one was resolving at the time of death from other causes, she said.

“We found no evidence of association with age, conditioning regimen, SOS prophylaxis, cumulative InO exposure, or time from InO to transplant, bearing in mind that it is a small number of cases, so analysis is limited,” she added.

Central CD22 evaluation in 27 patients with pre– and post–cycle 1 samples showed that 11 of those patients had residual disease at the end of cycle 1.

“There is clearly a subset of patients for whom the resistance mechanism does not seem to have any bearing on CD22, as it was still highly expressed at the time of relapse, but there are a significant number of patients who have downregulation of CD22 expression or a subset of blasts that were CD22 negative at the time of relapse,” she said. “Notably, two of three patients with baseline partial CD22 expression – so less than 90% ... did not achieve a morphologic complete response, and both of these patients had KMT2A rearrangements.”

The findings are important, because 10%-20% of children and young adults with B-ALL will relapse, and therapies that can bridge patients to HSCT or CAR T-cell therapy are critical for improving outcomes, Dr. O’Brien said, explaining that InO, a humanized CD22 IgG4 antibody conjugated to calicheamicin, was approved in adults based on “the impressive results from the INNOVATE trial, compared with chemotherapy,” but prospective data on its efficacy and safety in pediatric patients are lacking.

Retrospective data from a compassionate use program in children demonstrated a response rate of 67% in a heavily pretreated population, and phase 1 data from the ITCC-059 trial presented in a poster at the ASH meeting also showed “quite impressive results,” but a major concern has been hepatic toxicity, including SOS, she said.

Given the observed safety and efficacy in the current phase 2 trial, investigation in children will continue, she said, explaining that “COG is now undertaking a phase 3 trial – AALL1732 – which will randomize patients to chemotherapy [with or without] inotuzumab for patients aged 1-25 with newly diagnosed high-risk B-ALL.”

COG AALL1621 was funded by NCTN grants, St. Baldrick’s Foundation, and Pfizer. Dr. O’Brien reported research funding from Pfizer, Celgene, AbbVie, Amgen, Bristol-Myers Squibb, and BTG.

[email protected]

SOURCE: O’Brien M et al. ASH 2019, Abstract 741.

ORLANDO – Inotuzumab ozogamicin (InO), a CD22-targeted antibody approved for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), showed promising safety and efficacy in children and young adults with R/R B-ALL in a phase 2 trial.

Of 48 patients aged 1-21 years enrolled in the Children’s Oncology Group (COG) Protocol AALL1621 and evaluable for response and toxicity after treatment with the approved adult InO dose, 19 achieved a complete response (CR) and 9 achieved a complete response with incomplete count recovery (CRi) after the first treatment cycle, for an overall CR/CRi rate of 58.3%, Maureen M. O’Brien, MD, reported at the annual meeting of the American Society of Hematology.

Of those with CR/CRi, 19 (65.5%) achieved minimal residual disease less than 0.01%, said Dr. O’Brien, a pediatric hematologist and medical director of the Leukemia/Lymphoma Program at the Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center.

Three patients had a partial response (PR), nine had stable disease (SD), and eight had progressive disease (PD), and one of each with PR and SD achieved CR/CRi after a second treatment cycle.

“Of note, two patients who were characterized as [having] progressive disease actually had marrow complete response with incomplete count recovery, but had progressive CNS disease,” she said.

Patients included in the single-arm trial had CD22-positive B-ALL, defined as B-ALL with greater than 20% of blasts expressing CD22, and were in at least their second relapse, were refractory to two prior induction regimens, or had a relapse after hematopoietic stem cell transplantation (HSCT). One exception was that patients with Down syndrome were allowed inclusion after a first relapse, she noted.

Median patient age was 9 years, four patients had CNS 3 status, three had Down syndrome, and most were heavily pretreated, with 32 in at least their second relapse.

“Most patients had significant marrow disease burden, with a median marrow blast percentage of 81%,” Dr. O’Brien said. “In terms of prior therapy, 23% had prior transplant, 23% had prior CD19 [chimeric antigen receptor (CAR)] T-cell therapy – including two patients with prior CD22 CAR T, and 29% of patients had received prior blinatumomab.”

All patients received one cycle of InO at a dose of 1.8mg/m², with .8mg/m² given on day 1 and 0.5mg/m2 given on days 8 and 15. Intrathecal therapy was determined based on CNS status.

Patients with at least stable disease at day 28 were eligible for a second cycle; those with CR or CRi received InO at a dose of 0.5 mg/m² on days 1, 8, and 15 in cycle 2, and those without CR/CRi received the same fractionated dose as in cycle 1. Patients with CR/CRi after two cycles were eligible for up to six total cycles at investigator discretion, Dr. O’Brien explained, adding that 26 of 40 patients eligible for cycle 2 proceeded, including 13 of 18 with MRD less than .01%, 6 of 10 with MRD of 0.01% or greater, and 7 of 12 with PR/SD.

After cycle 2, all 13 with MRD less than .01% maintained that MRD level, 3 of 6 with MRD of .01% or greater achieved MRD less than .01%, 2 of 7 with PR/SD achieved CRi with MRD of .01% or greater – and one of those 2 was MRD negative after a third cycle.

Seven patients received three or more cycles.

“Therapy was extremely well tolerated,” Dr. O’Brien said, noting that the most common nonhematological grade 3 or higher adverse events occurring in at least 5% of patients in cycle 1 were febrile neutropenia and infection, occurring in 27.1% and 16.7% of patients, respectively. “But toxicity was quite minimal.”

Hepatic toxicity included four cases of grade 3 alanine transaminase and one grade 3 bilirubin toxicity in cycle 1, and one grade 3 ALT in cycle 2.

“Importantly, there were no inotuzumab dose modifications or delays due to hepatic toxicity,” she said.

Nine patients experienced 11 dose-limiting toxicities in cycle 1, including 7 involving prolonged count recovery beyond day 42, which was not attributable to disease, and 4 nonhematologic events, including drug reaction with eosinophilia and systemic symptoms, bronchopulmonary hemorrhage, respiratory distress, and a postintrathecal methotrexate stroke.

Sinusoidal obstruction syndrome (SOS) developed in 5 of the 48 patients, all in patients who underwent transplant after InO treatment. Only one of the five had undergone a prior transplant. All SOS cases were grade 3 and were treated with defibrotide; four cases resolved quickly, and one was resolving at the time of death from other causes, she said.

“We found no evidence of association with age, conditioning regimen, SOS prophylaxis, cumulative InO exposure, or time from InO to transplant, bearing in mind that it is a small number of cases, so analysis is limited,” she added.

Central CD22 evaluation in 27 patients with pre– and post–cycle 1 samples showed that 11 of those patients had residual disease at the end of cycle 1.

“There is clearly a subset of patients for whom the resistance mechanism does not seem to have any bearing on CD22, as it was still highly expressed at the time of relapse, but there are a significant number of patients who have downregulation of CD22 expression or a subset of blasts that were CD22 negative at the time of relapse,” she said. “Notably, two of three patients with baseline partial CD22 expression – so less than 90% ... did not achieve a morphologic complete response, and both of these patients had KMT2A rearrangements.”

The findings are important, because 10%-20% of children and young adults with B-ALL will relapse, and therapies that can bridge patients to HSCT or CAR T-cell therapy are critical for improving outcomes, Dr. O’Brien said, explaining that InO, a humanized CD22 IgG4 antibody conjugated to calicheamicin, was approved in adults based on “the impressive results from the INNOVATE trial, compared with chemotherapy,” but prospective data on its efficacy and safety in pediatric patients are lacking.

Retrospective data from a compassionate use program in children demonstrated a response rate of 67% in a heavily pretreated population, and phase 1 data from the ITCC-059 trial presented in a poster at the ASH meeting also showed “quite impressive results,” but a major concern has been hepatic toxicity, including SOS, she said.

Given the observed safety and efficacy in the current phase 2 trial, investigation in children will continue, she said, explaining that “COG is now undertaking a phase 3 trial – AALL1732 – which will randomize patients to chemotherapy [with or without] inotuzumab for patients aged 1-25 with newly diagnosed high-risk B-ALL.”

COG AALL1621 was funded by NCTN grants, St. Baldrick’s Foundation, and Pfizer. Dr. O’Brien reported research funding from Pfizer, Celgene, AbbVie, Amgen, Bristol-Myers Squibb, and BTG.

[email protected]

SOURCE: O’Brien M et al. ASH 2019, Abstract 741.

ORLANDO – Inotuzumab ozogamicin (InO), a CD22-targeted antibody approved for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), showed promising safety and efficacy in children and young adults with R/R B-ALL in a phase 2 trial.

Of 48 patients aged 1-21 years enrolled in the Children’s Oncology Group (COG) Protocol AALL1621 and evaluable for response and toxicity after treatment with the approved adult InO dose, 19 achieved a complete response (CR) and 9 achieved a complete response with incomplete count recovery (CRi) after the first treatment cycle, for an overall CR/CRi rate of 58.3%, Maureen M. O’Brien, MD, reported at the annual meeting of the American Society of Hematology.

Of those with CR/CRi, 19 (65.5%) achieved minimal residual disease less than 0.01%, said Dr. O’Brien, a pediatric hematologist and medical director of the Leukemia/Lymphoma Program at the Cancer and Blood Diseases Institute, Cincinnati Children’s Hospital Medical Center.

Three patients had a partial response (PR), nine had stable disease (SD), and eight had progressive disease (PD), and one of each with PR and SD achieved CR/CRi after a second treatment cycle.

“Of note, two patients who were characterized as [having] progressive disease actually had marrow complete response with incomplete count recovery, but had progressive CNS disease,” she said.

Patients included in the single-arm trial had CD22-positive B-ALL, defined as B-ALL with greater than 20% of blasts expressing CD22, and were in at least their second relapse, were refractory to two prior induction regimens, or had a relapse after hematopoietic stem cell transplantation (HSCT). One exception was that patients with Down syndrome were allowed inclusion after a first relapse, she noted.

Median patient age was 9 years, four patients had CNS 3 status, three had Down syndrome, and most were heavily pretreated, with 32 in at least their second relapse.

“Most patients had significant marrow disease burden, with a median marrow blast percentage of 81%,” Dr. O’Brien said. “In terms of prior therapy, 23% had prior transplant, 23% had prior CD19 [chimeric antigen receptor (CAR)] T-cell therapy – including two patients with prior CD22 CAR T, and 29% of patients had received prior blinatumomab.”

All patients received one cycle of InO at a dose of 1.8mg/m², with .8mg/m² given on day 1 and 0.5mg/m2 given on days 8 and 15. Intrathecal therapy was determined based on CNS status.

Patients with at least stable disease at day 28 were eligible for a second cycle; those with CR or CRi received InO at a dose of 0.5 mg/m² on days 1, 8, and 15 in cycle 2, and those without CR/CRi received the same fractionated dose as in cycle 1. Patients with CR/CRi after two cycles were eligible for up to six total cycles at investigator discretion, Dr. O’Brien explained, adding that 26 of 40 patients eligible for cycle 2 proceeded, including 13 of 18 with MRD less than .01%, 6 of 10 with MRD of 0.01% or greater, and 7 of 12 with PR/SD.

After cycle 2, all 13 with MRD less than .01% maintained that MRD level, 3 of 6 with MRD of .01% or greater achieved MRD less than .01%, 2 of 7 with PR/SD achieved CRi with MRD of .01% or greater – and one of those 2 was MRD negative after a third cycle.

Seven patients received three or more cycles.

“Therapy was extremely well tolerated,” Dr. O’Brien said, noting that the most common nonhematological grade 3 or higher adverse events occurring in at least 5% of patients in cycle 1 were febrile neutropenia and infection, occurring in 27.1% and 16.7% of patients, respectively. “But toxicity was quite minimal.”

Hepatic toxicity included four cases of grade 3 alanine transaminase and one grade 3 bilirubin toxicity in cycle 1, and one grade 3 ALT in cycle 2.

“Importantly, there were no inotuzumab dose modifications or delays due to hepatic toxicity,” she said.

Nine patients experienced 11 dose-limiting toxicities in cycle 1, including 7 involving prolonged count recovery beyond day 42, which was not attributable to disease, and 4 nonhematologic events, including drug reaction with eosinophilia and systemic symptoms, bronchopulmonary hemorrhage, respiratory distress, and a postintrathecal methotrexate stroke.

Sinusoidal obstruction syndrome (SOS) developed in 5 of the 48 patients, all in patients who underwent transplant after InO treatment. Only one of the five had undergone a prior transplant. All SOS cases were grade 3 and were treated with defibrotide; four cases resolved quickly, and one was resolving at the time of death from other causes, she said.

“We found no evidence of association with age, conditioning regimen, SOS prophylaxis, cumulative InO exposure, or time from InO to transplant, bearing in mind that it is a small number of cases, so analysis is limited,” she added.

Central CD22 evaluation in 27 patients with pre– and post–cycle 1 samples showed that 11 of those patients had residual disease at the end of cycle 1.

“There is clearly a subset of patients for whom the resistance mechanism does not seem to have any bearing on CD22, as it was still highly expressed at the time of relapse, but there are a significant number of patients who have downregulation of CD22 expression or a subset of blasts that were CD22 negative at the time of relapse,” she said. “Notably, two of three patients with baseline partial CD22 expression – so less than 90% ... did not achieve a morphologic complete response, and both of these patients had KMT2A rearrangements.”

The findings are important, because 10%-20% of children and young adults with B-ALL will relapse, and therapies that can bridge patients to HSCT or CAR T-cell therapy are critical for improving outcomes, Dr. O’Brien said, explaining that InO, a humanized CD22 IgG4 antibody conjugated to calicheamicin, was approved in adults based on “the impressive results from the INNOVATE trial, compared with chemotherapy,” but prospective data on its efficacy and safety in pediatric patients are lacking.

Retrospective data from a compassionate use program in children demonstrated a response rate of 67% in a heavily pretreated population, and phase 1 data from the ITCC-059 trial presented in a poster at the ASH meeting also showed “quite impressive results,” but a major concern has been hepatic toxicity, including SOS, she said.

Given the observed safety and efficacy in the current phase 2 trial, investigation in children will continue, she said, explaining that “COG is now undertaking a phase 3 trial – AALL1732 – which will randomize patients to chemotherapy [with or without] inotuzumab for patients aged 1-25 with newly diagnosed high-risk B-ALL.”

COG AALL1621 was funded by NCTN grants, St. Baldrick’s Foundation, and Pfizer. Dr. O’Brien reported research funding from Pfizer, Celgene, AbbVie, Amgen, Bristol-Myers Squibb, and BTG.

[email protected]

SOURCE: O’Brien M et al. ASH 2019, Abstract 741.

ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.

Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.

The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.

After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.

The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.

However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.

JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.

“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.

Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.

Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m² of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.

Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.

Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.

Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.

Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.

At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.

Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.

MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.

“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.

The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.

Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.

This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.

[email protected]

SOURCE: Sugiura I et al. ASH 2019. Abstract 743.

ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.

Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.

The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.

After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.

The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.

However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.

JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.

“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.

Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.

Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m² of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.

Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.

Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.

Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.

Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.

At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.

Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.

MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.

“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.

The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.

Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.

This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.

[email protected]

SOURCE: Sugiura I et al. ASH 2019. Abstract 743.

ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.

Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.

The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.

After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.

The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.

However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.

JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.

“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.

Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.

Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m² of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.

Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.

Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.

Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.

Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.

At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.

Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.

MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.

“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.

The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.

Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.

This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.

[email protected]

SOURCE: Sugiura I et al. ASH 2019. Abstract 743.