DLBCL

Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.

CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.

In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.

Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.

The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.

The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).

These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”

“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.

“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.

The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.

“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”

CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.

However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”

Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
 

[email protected]

Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.

CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.

In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.

Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.

The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.

The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).

These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”

“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.

“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.

The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.

“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”

CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.

However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”

Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
 

[email protected]

Is it time to consider chimeric antigen receptor (CAR) T-cell therapy for all relapsed/refractory diffuse large B-cell lymphoma patients? Maybe not, according to Andrew Zelenetz, MD, PhD.

CAR T-cell therapy has demonstrated activity in relapsed/refractory non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma (DLBCL), transformed indolent NHL, and mantle cell lymphoma, and can provide durable complete responses in a portion of patients with chemorefractory disease, Dr. Zelenetz, chair of the National Comprehensive Cancer Network Lymphoma Guidelines Panel and a specialist in lymphoma at Memorial Sloan Kettering Cancer Center in New York, said at the NCCN Hematologic Malignancies Annual Congress.

In chemosensitive patients, however, its role requires further examination, especially given findings from a recent analysis of patients from the Center for International Blood & Marrow Transplant Research (CIBMTR) registry showing comparable outcomes with high-dose chemotherapy and autologous stem cell rescue for patients with a positron emission testing–positive partial response (PR) after second-line chemotherapy, he said.

Of 249 patients who underwent a first autologous transplant for DLBCL between 2003 and 2018, received front-line rituximab chemotherapy, and had PET– or computed tomography–positive disease prior to transplant, 182 had early chemotherapy failure (within 12 months) and 67 had late chemotherapy failure (at 12 months or later) after therapy, according to findings from the study as reported at ASCO 2020.

The adjusted nonrelapse mortality rates in the early- and late-failure patients, respectively, were not significantly different at 7% and 3% at 1 year, and at 10% and 8% at 5 years. The corresponding progression/relapse rates were 41% and 35% at 1 year and 48% and 57% at 5 years; these were also not significantly different.

The adjusted progression-free survival (PFS) and overall survival (OS) in the groups at 5 years also did not differ significantly (PFS of 41% in both the early- and late-failure groups, and OS of 51% and 63%, respectively).

These outcomes are comparable to those seen with CAR T-cell therapy in refractory DLBCL patients in trials of CAR T-cell products, including the ZUMA-1 study of axicabtagene cyloleucel (Yescarta), which, in a 2019 update, showed survival plateaus of about 40% vs. the 5%-10% expected rate based on pre-CAR-T outcomes data; the JULIET trial of tisagenlecleucel (Kymriah), which showed survival plateaus in the range of 30%-35%; and the recently published TRANSCEND study of the investigational modified CAR-T product, lisocabtagene maraleucel, which also showed survival plateaus “in the range of 40%.”

“So all three agents are showing that CAR T cells represent a new treatment for diffuse large B-cell lymphoma in the relapsed/refractory setting,” Dr. Zelenetz said. “And as a result, [CAR T-cell therapy has] been included in the NCCN guidelines for transformed follicular lymphoma, for transformed marginal zone lymphoma, and for diffuse large B-cell lymphoma, as well as for refractory large B-cell lymphoma.

“But are CAR T cells absolutely required? Generally what we consider these days is that if you’re not in a PET-negative CR prior to high-dose therapy stem cell rescue, you should go on to CAR T cells,” Dr. Zelenetz said.

The analysis based on the CIBMTR registry data, however, suggests there may be other alternatives.

“The bottom line is that nonrelapse mortality was very low. Progression occurred in about half of the patients, but if we look at the overall and progression-free survival curves, there’s a plateau at around 45%,” Dr. Zelenetz said, explaining that the results are “very similar to the results that we’re getting in third-line treatment with CAR T cells, and this is a very similar population [of] PET-positive patients after second-line chemotherapy.”

CAR T-cell therapy can provide a durable CR in a portion of chemorefractory patients, and although there is room for improvement, “this represents a major step forward for these patients,” he said.

However, it’s not clear that CAR T cells are clearly superior to high-dose therapy and stem cell rescue for chemosensitive patients, he added, noting that “additional randomized trials are needed to answer this question, and they are ongoing as we speak.”

Dr. Zelenetz reported clinical research support or data safety monitoring board activity for BeiGene, Genentech, Juno Therapeutics, and MEI Pharma, and scientific advisory board, consulting, or expert witness activity for Celgene Corporation, Curries, Genentech, Gilead Sciences, Janssen Pharmaceutical Products, and several other pharmaceutical and biotechnology companies.
 

[email protected]

The Food and Drug Administration recently approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT).

In an interview, Ann S. LaCasce, MD, a lymphoma specialist, associate professor of medicine at Harvard Medical School, and director of the Dana-Farber/Massachusetts General Brigham fellowship in hematology/oncology, discussed the drug and its approval:

Question: How common is relapsed or refractory DLBCL? Have there been any changes in the rates of this disease in recent years?

Dr. LaCasce: Approximately 40% of patients with DLBCL will have relapsed or refractory disease. The rates of lymphoma have been rising over the past several decades for unclear reasons. As this is a disease predominantly of older adults, increasing life expectancy likely plays a role. Environmental factors may also be contributing.

Q: How long do patients with relapsed or refractory DLBCL who are not eligible for stem cell transplant usually survive?

Dr. LaCasce: This is highly variable, though it’s estimated to be approximately 1 year. Some patients will be cured with autologous transplantation or CAR-T cells. The pace of the disease can be highly variable, with some patients responding to multiple lines of therapy whereas others may have rapidly progressive refractory disease.

Q: What makes patients with relapsed or refractory DLBCL ineligible for ASCT?

Dr. LaCasce: To be eligible, patients need to be younger than 70-75 years or so without significant comorbidities and must have chemotherapy-responsive disease. More than half of patients will not fit these criteria.

Q: Can you briefly describe the L-MIND study that led to the approval of tafasitamab-cxix?

Dr. LaCasce: This was a single-arm, phase 2 study of tafasitamab plus lenalidomide in patients with relapsed/refractory DLBCL status after one to three prior regimens who were not candidates for ASCT. Patients received tafasitamab until progression and up to 1 year of lenalidomide. The median age was 72 years, and 50% of patients had received only one prior line of therapy.

The overall and complete response rates in 80 patients treated were 60% and 43%, respectively. The median progression-free survival was approximately 1 year. Nearly half of patients required dose reduction of lenalidomide, and about a quarter discontinued the drug. Twenty-five percent of patients discontinued therapy for adverse events.

Q: What’s the toxicity profile of tafasitamab-cxix?

Dr. LaCasce: The most common adverse events were infusion reactions and myelosuppression, which are managed with standard approaches to incident rate ratios with steroids, antihistamines, etc. Myelosuppression can occur, but in this combination is mostly driven by lenalidomide, which is dose reduced or discontinued.

Q: Where does tafasitamab-cxix fit in the treatment paradigm for relapsed or refractory DLBCL? How does it compare with other available options?

Dr. LaCasce: This is an option for patients who are not candidates for potentially curative approaches, including ASCT and CAR T-cell therapy. There are patients not eligible for ASCT who may be appropriate for CAR-T.

Tafasitamab plus lenalidomide requires frequent visits, particularly during the first 3 months, and then every other week until progression. The dose of lenalidomide will not be tolerable for many of these patients.

Other options in this population include polatuzumab plus bendamustine/rituximab or possibly selinexor. The former has similar activity and is time limited, though many patients will not tolerate the full dose of bendamustine. In the study leading to approval, selinexor had a much lower response rate of approximately 30%, and the patient population was much more favorable, given that eligibility required 60-98 days after last therapy before enrolling.

The only approval specific for nontransplant patients is tafasitamab/lenalidomide.

Q: From a cost standpoint, how does tafasitamab compare with other options in this patient population?

Dr. LaCasce: I don’t have exact figures, but all options are very expensive. CAR-T is the most expensive. Given the ongoing therapy of tafasitamab until progression, the cumulative cost could be very high. Polatuzumab plus bendamustine/rituximab and selinexor are also very costly.

Q: What other drugs are in development for relapsed or refractory DLBCL?

Dr. LaCasce: Novel CAR T-cell therapies, including lisocabtagene maraleucel that is at the FDA, are in development. Bispecific antibodies (REGN1979 and mosunetuzumab), combinations with CD47 antibodies, and loncastuximab tesirine are all in phase 2 trials.

Dr. LaCasce has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration recently approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT).

In an interview, Ann S. LaCasce, MD, a lymphoma specialist, associate professor of medicine at Harvard Medical School, and director of the Dana-Farber/Massachusetts General Brigham fellowship in hematology/oncology, discussed the drug and its approval:

Question: How common is relapsed or refractory DLBCL? Have there been any changes in the rates of this disease in recent years?

Dr. LaCasce: Approximately 40% of patients with DLBCL will have relapsed or refractory disease. The rates of lymphoma have been rising over the past several decades for unclear reasons. As this is a disease predominantly of older adults, increasing life expectancy likely plays a role. Environmental factors may also be contributing.

Q: How long do patients with relapsed or refractory DLBCL who are not eligible for stem cell transplant usually survive?

Dr. LaCasce: This is highly variable, though it’s estimated to be approximately 1 year. Some patients will be cured with autologous transplantation or CAR-T cells. The pace of the disease can be highly variable, with some patients responding to multiple lines of therapy whereas others may have rapidly progressive refractory disease.

Q: What makes patients with relapsed or refractory DLBCL ineligible for ASCT?

Dr. LaCasce: To be eligible, patients need to be younger than 70-75 years or so without significant comorbidities and must have chemotherapy-responsive disease. More than half of patients will not fit these criteria.

Q: Can you briefly describe the L-MIND study that led to the approval of tafasitamab-cxix?

Dr. LaCasce: This was a single-arm, phase 2 study of tafasitamab plus lenalidomide in patients with relapsed/refractory DLBCL status after one to three prior regimens who were not candidates for ASCT. Patients received tafasitamab until progression and up to 1 year of lenalidomide. The median age was 72 years, and 50% of patients had received only one prior line of therapy.

The overall and complete response rates in 80 patients treated were 60% and 43%, respectively. The median progression-free survival was approximately 1 year. Nearly half of patients required dose reduction of lenalidomide, and about a quarter discontinued the drug. Twenty-five percent of patients discontinued therapy for adverse events.

Q: What’s the toxicity profile of tafasitamab-cxix?

Dr. LaCasce: The most common adverse events were infusion reactions and myelosuppression, which are managed with standard approaches to incident rate ratios with steroids, antihistamines, etc. Myelosuppression can occur, but in this combination is mostly driven by lenalidomide, which is dose reduced or discontinued.

Q: Where does tafasitamab-cxix fit in the treatment paradigm for relapsed or refractory DLBCL? How does it compare with other available options?

Dr. LaCasce: This is an option for patients who are not candidates for potentially curative approaches, including ASCT and CAR T-cell therapy. There are patients not eligible for ASCT who may be appropriate for CAR-T.

Tafasitamab plus lenalidomide requires frequent visits, particularly during the first 3 months, and then every other week until progression. The dose of lenalidomide will not be tolerable for many of these patients.

Other options in this population include polatuzumab plus bendamustine/rituximab or possibly selinexor. The former has similar activity and is time limited, though many patients will not tolerate the full dose of bendamustine. In the study leading to approval, selinexor had a much lower response rate of approximately 30%, and the patient population was much more favorable, given that eligibility required 60-98 days after last therapy before enrolling.

The only approval specific for nontransplant patients is tafasitamab/lenalidomide.

Q: From a cost standpoint, how does tafasitamab compare with other options in this patient population?

Dr. LaCasce: I don’t have exact figures, but all options are very expensive. CAR-T is the most expensive. Given the ongoing therapy of tafasitamab until progression, the cumulative cost could be very high. Polatuzumab plus bendamustine/rituximab and selinexor are also very costly.

Q: What other drugs are in development for relapsed or refractory DLBCL?

Dr. LaCasce: Novel CAR T-cell therapies, including lisocabtagene maraleucel that is at the FDA, are in development. Bispecific antibodies (REGN1979 and mosunetuzumab), combinations with CD47 antibodies, and loncastuximab tesirine are all in phase 2 trials.

Dr. LaCasce has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

The Food and Drug Administration recently approved tafasitamab-cxix (Monjuvi) in combination with lenalidomide for the treatment of adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low-grade lymphoma, who are not eligible for autologous stem cell transplant (ASCT).

In an interview, Ann S. LaCasce, MD, a lymphoma specialist, associate professor of medicine at Harvard Medical School, and director of the Dana-Farber/Massachusetts General Brigham fellowship in hematology/oncology, discussed the drug and its approval:

Question: How common is relapsed or refractory DLBCL? Have there been any changes in the rates of this disease in recent years?

Dr. LaCasce: Approximately 40% of patients with DLBCL will have relapsed or refractory disease. The rates of lymphoma have been rising over the past several decades for unclear reasons. As this is a disease predominantly of older adults, increasing life expectancy likely plays a role. Environmental factors may also be contributing.

Q: How long do patients with relapsed or refractory DLBCL who are not eligible for stem cell transplant usually survive?

Dr. LaCasce: This is highly variable, though it’s estimated to be approximately 1 year. Some patients will be cured with autologous transplantation or CAR-T cells. The pace of the disease can be highly variable, with some patients responding to multiple lines of therapy whereas others may have rapidly progressive refractory disease.

Q: What makes patients with relapsed or refractory DLBCL ineligible for ASCT?

Dr. LaCasce: To be eligible, patients need to be younger than 70-75 years or so without significant comorbidities and must have chemotherapy-responsive disease. More than half of patients will not fit these criteria.

Q: Can you briefly describe the L-MIND study that led to the approval of tafasitamab-cxix?

Dr. LaCasce: This was a single-arm, phase 2 study of tafasitamab plus lenalidomide in patients with relapsed/refractory DLBCL status after one to three prior regimens who were not candidates for ASCT. Patients received tafasitamab until progression and up to 1 year of lenalidomide. The median age was 72 years, and 50% of patients had received only one prior line of therapy.

The overall and complete response rates in 80 patients treated were 60% and 43%, respectively. The median progression-free survival was approximately 1 year. Nearly half of patients required dose reduction of lenalidomide, and about a quarter discontinued the drug. Twenty-five percent of patients discontinued therapy for adverse events.

Q: What’s the toxicity profile of tafasitamab-cxix?

Dr. LaCasce: The most common adverse events were infusion reactions and myelosuppression, which are managed with standard approaches to incident rate ratios with steroids, antihistamines, etc. Myelosuppression can occur, but in this combination is mostly driven by lenalidomide, which is dose reduced or discontinued.

Q: Where does tafasitamab-cxix fit in the treatment paradigm for relapsed or refractory DLBCL? How does it compare with other available options?

Dr. LaCasce: This is an option for patients who are not candidates for potentially curative approaches, including ASCT and CAR T-cell therapy. There are patients not eligible for ASCT who may be appropriate for CAR-T.

Tafasitamab plus lenalidomide requires frequent visits, particularly during the first 3 months, and then every other week until progression. The dose of lenalidomide will not be tolerable for many of these patients.

Other options in this population include polatuzumab plus bendamustine/rituximab or possibly selinexor. The former has similar activity and is time limited, though many patients will not tolerate the full dose of bendamustine. In the study leading to approval, selinexor had a much lower response rate of approximately 30%, and the patient population was much more favorable, given that eligibility required 60-98 days after last therapy before enrolling.

The only approval specific for nontransplant patients is tafasitamab/lenalidomide.

Q: From a cost standpoint, how does tafasitamab compare with other options in this patient population?

Dr. LaCasce: I don’t have exact figures, but all options are very expensive. CAR-T is the most expensive. Given the ongoing therapy of tafasitamab until progression, the cumulative cost could be very high. Polatuzumab plus bendamustine/rituximab and selinexor are also very costly.

Q: What other drugs are in development for relapsed or refractory DLBCL?

Dr. LaCasce: Novel CAR T-cell therapies, including lisocabtagene maraleucel that is at the FDA, are in development. Bispecific antibodies (REGN1979 and mosunetuzumab), combinations with CD47 antibodies, and loncastuximab tesirine are all in phase 2 trials.

Dr. LaCasce has disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

Systemic or hematopoietic stem cell transplantation (HSCT) treatment of HIV-positive lymphoma patients resulted in improved outcomes, compared with nonsystemic treatment, according to the results of a large database study.

Researchers Thejus T. Jayakrishnan, MD, and colleagues examined patients with lymphoma diagnosed between 2004 and 2015 from the National Cancer Database. Patients were categorized as HIV positive and HIV negative. First-line lymphoma treatment was categorized as no systemic therapy reported, systemic therapy, or HSCT. Multivariate analysis was used to predict treatment and survival, according to Dr. Jayakrishnan, a resident at the department of internal medicine, Allegheny Health Network, Pittsburgh.

A total of 11,160 HIV-positive vs. 349,607 HIV-negative patients were analyzed, including mostly men, with a comorbidity index of 0. The most common lymphoma among HIV-positive patients was diffuse large B-cell lymphoma, according to the report in Clinical Lymphoma, Myeloma & Leukemia.

Among HIV-positive patients, 792 had no systemic treatment, 10,328 underwent systemic treatment, and 40 received HSCT treatment. The results showed that treatment of HIV-positive lymphoma patients resulted in improved outcomes: 3-year overall survival was 43.6% for nonsystemic treatment versus 58.1% for systemic (hazard ratio, 0.56; 95% confidence interval, 0.52-0.61; P < .005) versus 62.2% for HSCT therapy (HR, 0.42; 95% CI, 0.14-1.3; P = .08), the lack of significance in the latter could be caused in part by the small number of patients treated. Outcomes for both treatment regimens were lower, however, compared with non-HIV patients.

“The present study demonstrates improvement in survival outcomes for HIV-positive patients with lymphoma with treatments when feasible, but these outcomes are poor when compared to HIV-negative patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Jayakrishnan TT et al. Clin Lymph Myeloma Leuk. 2020 Feb 20. doi: 10.1016/j.clml.2020.06.003.

Systemic or hematopoietic stem cell transplantation (HSCT) treatment of HIV-positive lymphoma patients resulted in improved outcomes, compared with nonsystemic treatment, according to the results of a large database study.

Researchers Thejus T. Jayakrishnan, MD, and colleagues examined patients with lymphoma diagnosed between 2004 and 2015 from the National Cancer Database. Patients were categorized as HIV positive and HIV negative. First-line lymphoma treatment was categorized as no systemic therapy reported, systemic therapy, or HSCT. Multivariate analysis was used to predict treatment and survival, according to Dr. Jayakrishnan, a resident at the department of internal medicine, Allegheny Health Network, Pittsburgh.

A total of 11,160 HIV-positive vs. 349,607 HIV-negative patients were analyzed, including mostly men, with a comorbidity index of 0. The most common lymphoma among HIV-positive patients was diffuse large B-cell lymphoma, according to the report in Clinical Lymphoma, Myeloma & Leukemia.

Among HIV-positive patients, 792 had no systemic treatment, 10,328 underwent systemic treatment, and 40 received HSCT treatment. The results showed that treatment of HIV-positive lymphoma patients resulted in improved outcomes: 3-year overall survival was 43.6% for nonsystemic treatment versus 58.1% for systemic (hazard ratio, 0.56; 95% confidence interval, 0.52-0.61; P < .005) versus 62.2% for HSCT therapy (HR, 0.42; 95% CI, 0.14-1.3; P = .08), the lack of significance in the latter could be caused in part by the small number of patients treated. Outcomes for both treatment regimens were lower, however, compared with non-HIV patients.

“The present study demonstrates improvement in survival outcomes for HIV-positive patients with lymphoma with treatments when feasible, but these outcomes are poor when compared to HIV-negative patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Jayakrishnan TT et al. Clin Lymph Myeloma Leuk. 2020 Feb 20. doi: 10.1016/j.clml.2020.06.003.

Systemic or hematopoietic stem cell transplantation (HSCT) treatment of HIV-positive lymphoma patients resulted in improved outcomes, compared with nonsystemic treatment, according to the results of a large database study.

Researchers Thejus T. Jayakrishnan, MD, and colleagues examined patients with lymphoma diagnosed between 2004 and 2015 from the National Cancer Database. Patients were categorized as HIV positive and HIV negative. First-line lymphoma treatment was categorized as no systemic therapy reported, systemic therapy, or HSCT. Multivariate analysis was used to predict treatment and survival, according to Dr. Jayakrishnan, a resident at the department of internal medicine, Allegheny Health Network, Pittsburgh.

A total of 11,160 HIV-positive vs. 349,607 HIV-negative patients were analyzed, including mostly men, with a comorbidity index of 0. The most common lymphoma among HIV-positive patients was diffuse large B-cell lymphoma, according to the report in Clinical Lymphoma, Myeloma & Leukemia.

Among HIV-positive patients, 792 had no systemic treatment, 10,328 underwent systemic treatment, and 40 received HSCT treatment. The results showed that treatment of HIV-positive lymphoma patients resulted in improved outcomes: 3-year overall survival was 43.6% for nonsystemic treatment versus 58.1% for systemic (hazard ratio, 0.56; 95% confidence interval, 0.52-0.61; P < .005) versus 62.2% for HSCT therapy (HR, 0.42; 95% CI, 0.14-1.3; P = .08), the lack of significance in the latter could be caused in part by the small number of patients treated. Outcomes for both treatment regimens were lower, however, compared with non-HIV patients.

“The present study demonstrates improvement in survival outcomes for HIV-positive patients with lymphoma with treatments when feasible, but these outcomes are poor when compared to HIV-negative patients,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Jayakrishnan TT et al. Clin Lymph Myeloma Leuk. 2020 Feb 20. doi: 10.1016/j.clml.2020.06.003.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

The Food and Drug Administration has granted accelerated approval of selinexor, a nuclear transport inhibitor, for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Selinexor (marketed as XPOVIO by Karyopharm Therapeutics) is intended for adult patients with relapsed/refractory DLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy, according to the FDA’s announcement.

The FDA granted selinexor accelerated approval for this indication based on the response rate seen in the SADAL trial. Continued approval for this indication “may be contingent upon verification and description of clinical benefit in confirmatory trials,” according to the FDA.

The SADAL trial (NCT02227251) was a phase 2, single-arm, open-label study of patients with DLBCL who had previously received two to five systemic regimens. The patients received selinexor at 60 mg orally on days 1 and 3 of each week.

Results in 134 patients showed an overall response rate of 29% (95% confidence interval: 22-38), with complete responses in 13% of patients. Of 39 patients who achieved a partial or complete response, 38% had a response duration of at least 6 months, and 15% had a response duration of at least 12 months, according to the FDA announcement.

The most common adverse reactions in this trial were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities occurred in 15% or more of the patients, and comprised thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

Serious adverse reactions occurred in 46% of patients, most often from infection. Gastrointestinal toxicity occurred in 80% of patients, and any-grade hyponatremia occurred in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes, according to the announcement.

Warnings and precautions for adverse events – including thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-fetal toxicity – are provided in the prescribing information.

Selinexor acts through the inhibition of exportin-1 and leads to an accumulation of tumor suppressor proteins, a reduction in oncoproteins, and apoptosis of cancer cells. The drug was previously approved in 2019 for the treatment of relapsed/refractory multiple myeloma.

The SADAL trial was sponsored by Karyopharm Therapeutics.

[email protected]

SOURCE: U.S. Food and Drug Administration. 2020. Approval announcement.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

For patients with newly diagnosed, high-risk diffuse large B-cell lymphoma (DLBCL), adding avadomide to standard therapy may reduce the likelihood of treatment failure, based on phase 1 results.

The regimen was well tolerated and had a complete response rate of 79%, reported lead author Neha Mehta-Shah, MD, of Washington University, St. Louis, who presented findings as part of the American Society of Clinical Oncology virtual scientific program.

Newly diagnosed DLBCL “remains a clinical challenge,” Dr. Mehta-Shah said, noting a treatment failure rate of 30%-50% for standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP-21), and worse outcomes among patients with high-risk disease.

In an effort to boost efficacy, the investigators turned to avadomide, a cereblon E3 ligase modulator, which previously demonstrated a complete response rate of 11% when used as monotherapy for patients with relapsed or refractory DLBCL.

The present phase 1 data included 35 adults with newly diagnosed DLBCL who had measurable lesions of at least 2.0 cm and International Prognostic Indices (IPI) between 3-5. Specifically, 51% of patients had an IPI of 3, while 49% had an IPI of 4-5.

All patients received standard R-CHOP with pegfilgrastim (to stimulate white blood cell growth), plus escalating doses of oral avadomide from 1-3 mg. Treatment was delivered, when tolerated, for up to six 21-day cycles. Depending on dose level, avadomide was given during either 2 or 3 out of 3 weeks. During treatment weeks, avadomide was given on 5 of 7 days.

The primary objectives were safety, tolerability, and complete response rate. Secondary objectives included biomarkers and additional efficacy measures, while exploratory analyses were also conducted to assess pharmacokinetics and pharmacodynamics.

Out of 34 patients evaluable for efficacy, the complete response rate was 79% and the objective response rate was 88%. After a median follow-up of 10 months, the 1-year progression-free survival rate was 80%.

“The combination showed promising efficacy,” Dr. Mehta-Shah said.

The regimen was also well tolerated and demonstrated an “acceptable safety profile consistent with either therapy alone,” Dr. Mehta-Shah added.

Most patients (91%) completed all six cycles of therapy. Median relative total dose intensities were 99% and 95% for avadomide and R-CHOP-21, respectively. Approximately two out of three patients (66%) required dose interruptions of avadomide, and 9% required dose reductions because of adverse events.

Dose-limiting toxicities occurred in six patients, including sepsis, febrile neutropenia caused by skin infections, febrile neutropenia with hypotension, febrile neutropenia, pneumonia, and neutropenia with bacterial hepatic infection. Based on these findings, the recommended phase 2 dose of avadomide was determined to be 3 mg given during 2 out of 3 weeks.

About 74% of patients had grade 3-4 treatment-emergent adverse events, the most common of which were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and febrile neutropenia (11%).

During the second cycle of therapy, one patient died because of concurrent pneumonia. After completion of therapy, two patients developed cardiac failure, and data gathered after each cycle showed that five patients had developed elevated levels of troponin or brain natriuretic peptide.

Flow cytometry showed that avadomide had proimmunomodulatory effects, including expansion of memory T-cell populations and enhanced proliferation of T cells and NK cells. The magnitude of this latter increase was greater than that observed in previous studies involving R-CHOP and durvalumab, Dr. Mehta-Shah noted.

“We look forward to following up on this data regarding the progression-free survival over a longer period of time,” Dr. Mehta-Shah said. “The results of this trial indicate that further evaluation of cereblon-modulating compounds combined with immunochemotherapy for patients with previously untreated diffuse large B-cell lymphoma is worthy of further exploration.”

Invited discussant Edward Yeh, MD, of the University of Missouri–Columbia, called cereblon modulators such as avadomide and thalidomide a “very exciting class of anticancer therapy.”

In a virtual presentation, Dr. Yeh noted that cereblon modulators have several advantages, including “good absorption, distribution, metabolism, [and] elimination,” plus relatively low susceptibility to mutation-directed drug resistance.

Despite some drawbacks, including difficulty to design and synthesize, Dr. Yeh suggested that this drug class may play a bigger role over time.

“We’re expecting more cancer therapy to come to fruition through the utilization of this posttranslational, protein-modification pathway,” he concluded.

The study was funded by Celgene. The investigators disclosed additional relationships with Kyowa Hakko Kirin, AstraZeneca, Roche, and others.

SOURCE: Mehta-Shah N et al. ASCO 2020, Abstract 3501.

Exposure to carcinogens has been implicated in the development of non-Hodgkin lymphoma (NHL), suggesting that an examination of the environment on a population-based level might provide some insights. On that basis, researchers performed a study that found that living in an urban vs. rural area was associated with an increased risk of developing non-Hodgkin lymphoma (NHL) among diverse, urban populations.

The study, published online in Clinical Lymphoma, Myeloma & Leukemia, found an increased incidence of diffuse large B-cell lymphoma (DLBCL) in urban vs. rural Hispanics, and a similar increased incidence of chronic lymphocytic leukemia (CLL) in non-metropolitan urban non-Hispanic blacks.

A total of 482,096 adults aged 20 years and older with incident NHL were reported to 21 Surveillance, Epidemiology,and End Results (SEER) population-based registries for the period 2000 to 2016. Deanna Blansky of the Albert Einstein College of Medicine, Bronx, N.Y., and her colleagues compared patients by NHL subtype and urban-rural status, using rural-urban continuum codes from the U.S. Department of Agriculture.

The researchers found 136,197 DLBCL, 70,882 follicular lymphoma (FL), and 120,319 CLL cases of patients aged ≥ 20 years. The DLBCL patients comprised 73.6% non-Hispanic white, 11.8% Hispanic, and 7.3% non-Hispanic black, with a similar distribution observed for FL and CLL. Patients were adjusted for age, sex, and family poverty.

The study showed that, overall, there was a higher DLBCL incidence rate in metropolitan urban areas, compared with rural areas overall (incidence rate ratio [IRR] = 1.20, 95% confidence interval [CI] 1.11-1.30). Most pronounced was an increased DLBCL incidence among Hispanics in urban areas, compared with rural areas (rural IRR = 1.00; non-metropolitan urban IRR = 1.32, 95% CI 1.16-1.51; metropolitan urban = 1.55, 95% CI 1.36-1.76).

In contrast, metropolitan urban areas had a lower overall incidence of CLL than rural areas (8.4 vs. 9.7 per 100,000; IRR = .87; 95% CI .86-.89).

However, increased CLL incidence rates were found to be associated with non-metropolitan urban areas, compared with rural areas (IRR = 1.19; 95% CI 1.10-1.28), particularly among non-Hispanic Blacks (IRR = 1.49, 95% CI 1.27-1.72).

Unlike DLBCL and CLL, there were no differences observed in FL incidence rates by urban-rural status after adjusting for age, sex, and family poverty rates, the researchers reported.

“Overall, our findings suggest that factors related to urban status may be associated with DLBCL and CLL pathogenesis. Our results may help provide epidemiological clues to understanding the racial disparities seen among hematological malignancies, particularly regarding the risk of DLBCL in Hispanics and CLL in non-Hispanic Blacks,” the researchers concluded.

The study was sponsored by the U.S. National Institutes of Health. The researchers did not report conflict information.
 

[email protected]

SOURCE: Blansky D et al. Clin Lymphoma Myeloma Leuk. 2020 May 15; doi.org/10.1016/j.clml.2020.05.010.

Exposure to carcinogens has been implicated in the development of non-Hodgkin lymphoma (NHL), suggesting that an examination of the environment on a population-based level might provide some insights. On that basis, researchers performed a study that found that living in an urban vs. rural area was associated with an increased risk of developing non-Hodgkin lymphoma (NHL) among diverse, urban populations.

The study, published online in Clinical Lymphoma, Myeloma & Leukemia, found an increased incidence of diffuse large B-cell lymphoma (DLBCL) in urban vs. rural Hispanics, and a similar increased incidence of chronic lymphocytic leukemia (CLL) in non-metropolitan urban non-Hispanic blacks.

A total of 482,096 adults aged 20 years and older with incident NHL were reported to 21 Surveillance, Epidemiology,and End Results (SEER) population-based registries for the period 2000 to 2016. Deanna Blansky of the Albert Einstein College of Medicine, Bronx, N.Y., and her colleagues compared patients by NHL subtype and urban-rural status, using rural-urban continuum codes from the U.S. Department of Agriculture.

The researchers found 136,197 DLBCL, 70,882 follicular lymphoma (FL), and 120,319 CLL cases of patients aged ≥ 20 years. The DLBCL patients comprised 73.6% non-Hispanic white, 11.8% Hispanic, and 7.3% non-Hispanic black, with a similar distribution observed for FL and CLL. Patients were adjusted for age, sex, and family poverty.

The study showed that, overall, there was a higher DLBCL incidence rate in metropolitan urban areas, compared with rural areas overall (incidence rate ratio [IRR] = 1.20, 95% confidence interval [CI] 1.11-1.30). Most pronounced was an increased DLBCL incidence among Hispanics in urban areas, compared with rural areas (rural IRR = 1.00; non-metropolitan urban IRR = 1.32, 95% CI 1.16-1.51; metropolitan urban = 1.55, 95% CI 1.36-1.76).

In contrast, metropolitan urban areas had a lower overall incidence of CLL than rural areas (8.4 vs. 9.7 per 100,000; IRR = .87; 95% CI .86-.89).

However, increased CLL incidence rates were found to be associated with non-metropolitan urban areas, compared with rural areas (IRR = 1.19; 95% CI 1.10-1.28), particularly among non-Hispanic Blacks (IRR = 1.49, 95% CI 1.27-1.72).

Unlike DLBCL and CLL, there were no differences observed in FL incidence rates by urban-rural status after adjusting for age, sex, and family poverty rates, the researchers reported.

“Overall, our findings suggest that factors related to urban status may be associated with DLBCL and CLL pathogenesis. Our results may help provide epidemiological clues to understanding the racial disparities seen among hematological malignancies, particularly regarding the risk of DLBCL in Hispanics and CLL in non-Hispanic Blacks,” the researchers concluded.

The study was sponsored by the U.S. National Institutes of Health. The researchers did not report conflict information.
 

[email protected]

SOURCE: Blansky D et al. Clin Lymphoma Myeloma Leuk. 2020 May 15; doi.org/10.1016/j.clml.2020.05.010.

Exposure to carcinogens has been implicated in the development of non-Hodgkin lymphoma (NHL), suggesting that an examination of the environment on a population-based level might provide some insights. On that basis, researchers performed a study that found that living in an urban vs. rural area was associated with an increased risk of developing non-Hodgkin lymphoma (NHL) among diverse, urban populations.

The study, published online in Clinical Lymphoma, Myeloma & Leukemia, found an increased incidence of diffuse large B-cell lymphoma (DLBCL) in urban vs. rural Hispanics, and a similar increased incidence of chronic lymphocytic leukemia (CLL) in non-metropolitan urban non-Hispanic blacks.

A total of 482,096 adults aged 20 years and older with incident NHL were reported to 21 Surveillance, Epidemiology,and End Results (SEER) population-based registries for the period 2000 to 2016. Deanna Blansky of the Albert Einstein College of Medicine, Bronx, N.Y., and her colleagues compared patients by NHL subtype and urban-rural status, using rural-urban continuum codes from the U.S. Department of Agriculture.

The researchers found 136,197 DLBCL, 70,882 follicular lymphoma (FL), and 120,319 CLL cases of patients aged ≥ 20 years. The DLBCL patients comprised 73.6% non-Hispanic white, 11.8% Hispanic, and 7.3% non-Hispanic black, with a similar distribution observed for FL and CLL. Patients were adjusted for age, sex, and family poverty.

The study showed that, overall, there was a higher DLBCL incidence rate in metropolitan urban areas, compared with rural areas overall (incidence rate ratio [IRR] = 1.20, 95% confidence interval [CI] 1.11-1.30). Most pronounced was an increased DLBCL incidence among Hispanics in urban areas, compared with rural areas (rural IRR = 1.00; non-metropolitan urban IRR = 1.32, 95% CI 1.16-1.51; metropolitan urban = 1.55, 95% CI 1.36-1.76).

In contrast, metropolitan urban areas had a lower overall incidence of CLL than rural areas (8.4 vs. 9.7 per 100,000; IRR = .87; 95% CI .86-.89).

However, increased CLL incidence rates were found to be associated with non-metropolitan urban areas, compared with rural areas (IRR = 1.19; 95% CI 1.10-1.28), particularly among non-Hispanic Blacks (IRR = 1.49, 95% CI 1.27-1.72).

Unlike DLBCL and CLL, there were no differences observed in FL incidence rates by urban-rural status after adjusting for age, sex, and family poverty rates, the researchers reported.

“Overall, our findings suggest that factors related to urban status may be associated with DLBCL and CLL pathogenesis. Our results may help provide epidemiological clues to understanding the racial disparities seen among hematological malignancies, particularly regarding the risk of DLBCL in Hispanics and CLL in non-Hispanic Blacks,” the researchers concluded.

The study was sponsored by the U.S. National Institutes of Health. The researchers did not report conflict information.
 

[email protected]

SOURCE: Blansky D et al. Clin Lymphoma Myeloma Leuk. 2020 May 15; doi.org/10.1016/j.clml.2020.05.010.

Academic centers had significantly improved overall survival of patients with diffuse large B-cell lymphoma (DLBCL), according to a large database study.

Nephron/Wikimedia Commons/CC BY-SA 3.0

Researchers used the U.S. National Cancer Database to identify patients with a diagnosis of DLBCL from 2004 to 2015. The researchers identified 27,690 patients for the study. The majority of the patients were white (89.3%) and men (53.7%), with an average age of 64 years. A total of 57.6% of the patients had been treated at nonacademic centers and 42.4% at academic centers, and no notable differences were seen in facility choice among the low- to high-risk International Prognostic Index (IPI) risk categories.

The researchers found that overall survival of the DLBCL patients at academic centers was 108.3 months versus 74.5 months at nonacademic centers (P < .001), according to the study published in Clinical Lymphoma, Myeloma and Leukemia.

In addition, the median survival for patients with high-risk disease treated at academic centers was more than twice that of high-risk patients treated at nonacademic centers (33.5 months vs. 14.4 months, respectively; P < .001). Although the median survival for the other risk categories was also improved, the difference was less pronounced in the groups with lower IPI scores, according to the researchers.

Long-term overall survival for all patients with DLBCL at academic centers was significantly improved at both 5 and 10 years (59% and 43% survival, respectively) compared with those patients treated at nonacademic centers (51% and 35% survival, respectively; P < .001).

Speculating on factors that might be involved in this discrepancy in survival, the researchers suggested that academic centers might provide increased access to clinical trials, improved physician expertise, as well as improved treatment facilities and supportive care.

“Our results should prompt further investigation in precisely determining the factors that might support this significant effect on decreased survival among those treated in the community and help ameliorate this discrepancy,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Ermann DA et al. Clin Lymphoma Myeloma Leuk. 2020;20(4): e17483.

Academic centers had significantly improved overall survival of patients with diffuse large B-cell lymphoma (DLBCL), according to a large database study.

Nephron/Wikimedia Commons/CC BY-SA 3.0

Researchers used the U.S. National Cancer Database to identify patients with a diagnosis of DLBCL from 2004 to 2015. The researchers identified 27,690 patients for the study. The majority of the patients were white (89.3%) and men (53.7%), with an average age of 64 years. A total of 57.6% of the patients had been treated at nonacademic centers and 42.4% at academic centers, and no notable differences were seen in facility choice among the low- to high-risk International Prognostic Index (IPI) risk categories.

The researchers found that overall survival of the DLBCL patients at academic centers was 108.3 months versus 74.5 months at nonacademic centers (P < .001), according to the study published in Clinical Lymphoma, Myeloma and Leukemia.

In addition, the median survival for patients with high-risk disease treated at academic centers was more than twice that of high-risk patients treated at nonacademic centers (33.5 months vs. 14.4 months, respectively; P < .001). Although the median survival for the other risk categories was also improved, the difference was less pronounced in the groups with lower IPI scores, according to the researchers.

Long-term overall survival for all patients with DLBCL at academic centers was significantly improved at both 5 and 10 years (59% and 43% survival, respectively) compared with those patients treated at nonacademic centers (51% and 35% survival, respectively; P < .001).

Speculating on factors that might be involved in this discrepancy in survival, the researchers suggested that academic centers might provide increased access to clinical trials, improved physician expertise, as well as improved treatment facilities and supportive care.

“Our results should prompt further investigation in precisely determining the factors that might support this significant effect on decreased survival among those treated in the community and help ameliorate this discrepancy,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Ermann DA et al. Clin Lymphoma Myeloma Leuk. 2020;20(4): e17483.

Academic centers had significantly improved overall survival of patients with diffuse large B-cell lymphoma (DLBCL), according to a large database study.

Nephron/Wikimedia Commons/CC BY-SA 3.0

Researchers used the U.S. National Cancer Database to identify patients with a diagnosis of DLBCL from 2004 to 2015. The researchers identified 27,690 patients for the study. The majority of the patients were white (89.3%) and men (53.7%), with an average age of 64 years. A total of 57.6% of the patients had been treated at nonacademic centers and 42.4% at academic centers, and no notable differences were seen in facility choice among the low- to high-risk International Prognostic Index (IPI) risk categories.

The researchers found that overall survival of the DLBCL patients at academic centers was 108.3 months versus 74.5 months at nonacademic centers (P < .001), according to the study published in Clinical Lymphoma, Myeloma and Leukemia.

In addition, the median survival for patients with high-risk disease treated at academic centers was more than twice that of high-risk patients treated at nonacademic centers (33.5 months vs. 14.4 months, respectively; P < .001). Although the median survival for the other risk categories was also improved, the difference was less pronounced in the groups with lower IPI scores, according to the researchers.

Long-term overall survival for all patients with DLBCL at academic centers was significantly improved at both 5 and 10 years (59% and 43% survival, respectively) compared with those patients treated at nonacademic centers (51% and 35% survival, respectively; P < .001).

Speculating on factors that might be involved in this discrepancy in survival, the researchers suggested that academic centers might provide increased access to clinical trials, improved physician expertise, as well as improved treatment facilities and supportive care.

“Our results should prompt further investigation in precisely determining the factors that might support this significant effect on decreased survival among those treated in the community and help ameliorate this discrepancy,” the researchers concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Ermann DA et al. Clin Lymphoma Myeloma Leuk. 2020;20(4): e17483.

A chimeric antigen receptor (CAR) construct using transduced natural killer cells instead of T cells was associated with a high complete remission rate without the cytokine release syndrome frequently seen with CAR T cell therapy, early clinical trial results show.

The construct, consisting of natural killer (NK) cells derived from umbilical cord blood that have been transduced to target CD19-expressing cells combined with interleukin 15 and equipped with an “off” switch, offers the prospect of an off-the-shelf CAR product, reported Enli Liu, MD, and colleagues at the University of Texas MD Anderson Cancer Center in Houston.

“We found that allogeneic CAR-NK cells can be delivered in adoptive transfer without the serious cytokine release syndrome and neurologic toxic effects that have been associated with CAR T-cell therapy,” they wrote in The New England Journal of Medicine.

The modified NK cells were delivered to 9 of 11 patients with only partial human leukocyte antigen (HLA) matching, and in 2 patients with no matching, yet there were no cases of graft-versus host disease (GvHD), and no patients had symptoms of cytokine release syndrome (CRS), neurotoxicity, or hemophagocytic lymphohistiocytosis.

CAR T cell production “is a cumbersome process that requires coordination and collection of the cells and there’s several weeks of manufacturing, during which time patients often can have their lymphoma worsen, and so at times it’s a little bit of a race against the clock to get those cells manufactured,” Brian Hill, MD, PhD, director of the lymphoid malignancies program at Taussig Cancer Institute at Cleveland Clinic, said in an interview.

Dr. Hill, who was not involved in the study, said that the proof-of-principle study shows promising early results and offers the prospect of an effective and safe off-the-shelf therapeutic option for patients with lymphoid malignancies.
 

Advanced B-cell cancers

The investigators conducted a phase 1/2 trial in patients with B-cell lymphoid malignancies, including five patients with chronic lymphocytic leukemia (CLL), one patient with Richter’s transformation and one with accelerated CLL, three with transformed follicular lymphoma, two with diffuse large B-cell lymphoma (DLBCL), and one with follicular lymphoma (focally grade 3B).

The patients were all heavily pretreated, with 3 to as many as 11 prior lines of therapy.

The patients received cord blood-derived NK cells that had been transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch.

The cells were expanded in the lab and after the patients underwent lymphodepleting chemotherapy, they received the cells in a single infusion at one of three doses, either 1×10⁵, 1×10⁶, or 1×10⁷ CAR-NK cells per kilogram of body weight.

As noted before, there were no cases of CRS, neurotoxicity, or GvHD and no increase over baseline in inflammatory cytokines, including interleukin-6, a key factor in the development and severity of CRS. The maximum tolerated dose was not reached.
 

Early efficacy

Of the 11 patients, 8 had a clinical response, and 7 had a complete remission, including 4 patients with lymphomas and 3 with CLL.

The patient with CLL with Richter’s transformation had a remission of the Richter’s component, but not of the CLL itself.

“This is particularly remarkable, because these patients are notoriously very difficult to treat, and the efficacy of autologous CAR T cell therapy in CLL and Richter’s patients has been hampered by lack of fitness of the patient’s own T cells when manufacturing the CAR T cell product, so this approach may obviate the need for autologous T cells in these patients,” Dr. Hill said.

The responses were rapid and occurred within 30 days of infusion at all dose levels. In addition, there was evidence of expansion and persistence of the modified NK cells at low levels for at least 1 year, despite the HLA mismatches between the NK cells and the recipients. The investigators speculated that the inclusion of interleukin-15 in the NL construct may at least partially account for the persistence of the cells and their antitumor activity.

Of the eight patients with a response, five had postremission therapy, including two patients with CLL who had minimal residual disease (MRD), one patient with follicular lymphoma and one with transformed follicular lymphoma who underwent hematopoietic stem-cell transplantation while in complete remission without evidence of MRD, and the patient with CLLL with Richter’s transformation with remission of the lymphoma component, who received a course of venetoclax.

The authors acknowledged that it may be difficult to assess the durability of response after CAR NK therapy in this study because of the allowed consolidation therapy for patients in remission.

They noted that although the patients in the current study each had a fresh CAR NK product manufactured for them, “we have shown that it is possible to produce more than 100 doses of CAR-NK cells from a single cord-blood unit. This capability, together with the apparently minimal HLA-matching requirements between the donor of CAR-NK cells and the patient, may pave the way for a truly off-the-shelf product that could increase treatment accessibility for many more patients.”

The National Institutes of Health supported the study. Dr. Liu disclosed a pending patent for methods of production of CAR-NK cells, and a patent held by MD Anderson for methods of treatment with NK cells. Dr. Hill is a member of the Hematology News editorial advisory board.

SOURCE: Liu E et al. N Engl J Med. 2020 Feb 6;382:545-53.

A chimeric antigen receptor (CAR) construct using transduced natural killer cells instead of T cells was associated with a high complete remission rate without the cytokine release syndrome frequently seen with CAR T cell therapy, early clinical trial results show.

The construct, consisting of natural killer (NK) cells derived from umbilical cord blood that have been transduced to target CD19-expressing cells combined with interleukin 15 and equipped with an “off” switch, offers the prospect of an off-the-shelf CAR product, reported Enli Liu, MD, and colleagues at the University of Texas MD Anderson Cancer Center in Houston.

“We found that allogeneic CAR-NK cells can be delivered in adoptive transfer without the serious cytokine release syndrome and neurologic toxic effects that have been associated with CAR T-cell therapy,” they wrote in The New England Journal of Medicine.

The modified NK cells were delivered to 9 of 11 patients with only partial human leukocyte antigen (HLA) matching, and in 2 patients with no matching, yet there were no cases of graft-versus host disease (GvHD), and no patients had symptoms of cytokine release syndrome (CRS), neurotoxicity, or hemophagocytic lymphohistiocytosis.

CAR T cell production “is a cumbersome process that requires coordination and collection of the cells and there’s several weeks of manufacturing, during which time patients often can have their lymphoma worsen, and so at times it’s a little bit of a race against the clock to get those cells manufactured,” Brian Hill, MD, PhD, director of the lymphoid malignancies program at Taussig Cancer Institute at Cleveland Clinic, said in an interview.

Dr. Hill, who was not involved in the study, said that the proof-of-principle study shows promising early results and offers the prospect of an effective and safe off-the-shelf therapeutic option for patients with lymphoid malignancies.
 

Advanced B-cell cancers

The investigators conducted a phase 1/2 trial in patients with B-cell lymphoid malignancies, including five patients with chronic lymphocytic leukemia (CLL), one patient with Richter’s transformation and one with accelerated CLL, three with transformed follicular lymphoma, two with diffuse large B-cell lymphoma (DLBCL), and one with follicular lymphoma (focally grade 3B).

The patients were all heavily pretreated, with 3 to as many as 11 prior lines of therapy.

The patients received cord blood-derived NK cells that had been transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch.

The cells were expanded in the lab and after the patients underwent lymphodepleting chemotherapy, they received the cells in a single infusion at one of three doses, either 1×10⁵, 1×10⁶, or 1×10⁷ CAR-NK cells per kilogram of body weight.

As noted before, there were no cases of CRS, neurotoxicity, or GvHD and no increase over baseline in inflammatory cytokines, including interleukin-6, a key factor in the development and severity of CRS. The maximum tolerated dose was not reached.
 

Early efficacy

Of the 11 patients, 8 had a clinical response, and 7 had a complete remission, including 4 patients with lymphomas and 3 with CLL.

The patient with CLL with Richter’s transformation had a remission of the Richter’s component, but not of the CLL itself.

“This is particularly remarkable, because these patients are notoriously very difficult to treat, and the efficacy of autologous CAR T cell therapy in CLL and Richter’s patients has been hampered by lack of fitness of the patient’s own T cells when manufacturing the CAR T cell product, so this approach may obviate the need for autologous T cells in these patients,” Dr. Hill said.

The responses were rapid and occurred within 30 days of infusion at all dose levels. In addition, there was evidence of expansion and persistence of the modified NK cells at low levels for at least 1 year, despite the HLA mismatches between the NK cells and the recipients. The investigators speculated that the inclusion of interleukin-15 in the NL construct may at least partially account for the persistence of the cells and their antitumor activity.

Of the eight patients with a response, five had postremission therapy, including two patients with CLL who had minimal residual disease (MRD), one patient with follicular lymphoma and one with transformed follicular lymphoma who underwent hematopoietic stem-cell transplantation while in complete remission without evidence of MRD, and the patient with CLLL with Richter’s transformation with remission of the lymphoma component, who received a course of venetoclax.

The authors acknowledged that it may be difficult to assess the durability of response after CAR NK therapy in this study because of the allowed consolidation therapy for patients in remission.

They noted that although the patients in the current study each had a fresh CAR NK product manufactured for them, “we have shown that it is possible to produce more than 100 doses of CAR-NK cells from a single cord-blood unit. This capability, together with the apparently minimal HLA-matching requirements between the donor of CAR-NK cells and the patient, may pave the way for a truly off-the-shelf product that could increase treatment accessibility for many more patients.”

The National Institutes of Health supported the study. Dr. Liu disclosed a pending patent for methods of production of CAR-NK cells, and a patent held by MD Anderson for methods of treatment with NK cells. Dr. Hill is a member of the Hematology News editorial advisory board.

SOURCE: Liu E et al. N Engl J Med. 2020 Feb 6;382:545-53.

A chimeric antigen receptor (CAR) construct using transduced natural killer cells instead of T cells was associated with a high complete remission rate without the cytokine release syndrome frequently seen with CAR T cell therapy, early clinical trial results show.

The construct, consisting of natural killer (NK) cells derived from umbilical cord blood that have been transduced to target CD19-expressing cells combined with interleukin 15 and equipped with an “off” switch, offers the prospect of an off-the-shelf CAR product, reported Enli Liu, MD, and colleagues at the University of Texas MD Anderson Cancer Center in Houston.

“We found that allogeneic CAR-NK cells can be delivered in adoptive transfer without the serious cytokine release syndrome and neurologic toxic effects that have been associated with CAR T-cell therapy,” they wrote in The New England Journal of Medicine.

The modified NK cells were delivered to 9 of 11 patients with only partial human leukocyte antigen (HLA) matching, and in 2 patients with no matching, yet there were no cases of graft-versus host disease (GvHD), and no patients had symptoms of cytokine release syndrome (CRS), neurotoxicity, or hemophagocytic lymphohistiocytosis.

CAR T cell production “is a cumbersome process that requires coordination and collection of the cells and there’s several weeks of manufacturing, during which time patients often can have their lymphoma worsen, and so at times it’s a little bit of a race against the clock to get those cells manufactured,” Brian Hill, MD, PhD, director of the lymphoid malignancies program at Taussig Cancer Institute at Cleveland Clinic, said in an interview.

Dr. Hill, who was not involved in the study, said that the proof-of-principle study shows promising early results and offers the prospect of an effective and safe off-the-shelf therapeutic option for patients with lymphoid malignancies.
 

Advanced B-cell cancers

The investigators conducted a phase 1/2 trial in patients with B-cell lymphoid malignancies, including five patients with chronic lymphocytic leukemia (CLL), one patient with Richter’s transformation and one with accelerated CLL, three with transformed follicular lymphoma, two with diffuse large B-cell lymphoma (DLBCL), and one with follicular lymphoma (focally grade 3B).

The patients were all heavily pretreated, with 3 to as many as 11 prior lines of therapy.

The patients received cord blood-derived NK cells that had been transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch.

The cells were expanded in the lab and after the patients underwent lymphodepleting chemotherapy, they received the cells in a single infusion at one of three doses, either 1×10⁵, 1×10⁶, or 1×10⁷ CAR-NK cells per kilogram of body weight.

As noted before, there were no cases of CRS, neurotoxicity, or GvHD and no increase over baseline in inflammatory cytokines, including interleukin-6, a key factor in the development and severity of CRS. The maximum tolerated dose was not reached.
 

Early efficacy

Of the 11 patients, 8 had a clinical response, and 7 had a complete remission, including 4 patients with lymphomas and 3 with CLL.

The patient with CLL with Richter’s transformation had a remission of the Richter’s component, but not of the CLL itself.

“This is particularly remarkable, because these patients are notoriously very difficult to treat, and the efficacy of autologous CAR T cell therapy in CLL and Richter’s patients has been hampered by lack of fitness of the patient’s own T cells when manufacturing the CAR T cell product, so this approach may obviate the need for autologous T cells in these patients,” Dr. Hill said.

The responses were rapid and occurred within 30 days of infusion at all dose levels. In addition, there was evidence of expansion and persistence of the modified NK cells at low levels for at least 1 year, despite the HLA mismatches between the NK cells and the recipients. The investigators speculated that the inclusion of interleukin-15 in the NL construct may at least partially account for the persistence of the cells and their antitumor activity.

Of the eight patients with a response, five had postremission therapy, including two patients with CLL who had minimal residual disease (MRD), one patient with follicular lymphoma and one with transformed follicular lymphoma who underwent hematopoietic stem-cell transplantation while in complete remission without evidence of MRD, and the patient with CLLL with Richter’s transformation with remission of the lymphoma component, who received a course of venetoclax.

The authors acknowledged that it may be difficult to assess the durability of response after CAR NK therapy in this study because of the allowed consolidation therapy for patients in remission.

They noted that although the patients in the current study each had a fresh CAR NK product manufactured for them, “we have shown that it is possible to produce more than 100 doses of CAR-NK cells from a single cord-blood unit. This capability, together with the apparently minimal HLA-matching requirements between the donor of CAR-NK cells and the patient, may pave the way for a truly off-the-shelf product that could increase treatment accessibility for many more patients.”

The National Institutes of Health supported the study. Dr. Liu disclosed a pending patent for methods of production of CAR-NK cells, and a patent held by MD Anderson for methods of treatment with NK cells. Dr. Hill is a member of the Hematology News editorial advisory board.

SOURCE: Liu E et al. N Engl J Med. 2020 Feb 6;382:545-53.