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CAR T-Cell Therapies for Relapsed/Refractory NHL

Insights From: Nilanjan Ghosh, MD, PhD, Levin Cancer Institute; Leo Gordon, MD, Northwestern Memorial Hospital; Matthew Lunning, DO, University of Nebraska Medical Center
Published: Friday, Nov 16, 2018



Transcript: 

Matthew Lunning, DO: Axi-cel is currently approved in those patients who have received greater than 2 lines of therapy and have biopsy-proven diffuse large B-cell lymphoma setting, primal mediastinal lymphoma, or those patients who have had an antecedent follicular lymphoma that is then evolved or transformed into diffuse large B-cell lymphoma.

Tisa-cel is similar in that it is approved for those patients who have relapsed/refractory diffuse large B-cell lymphoma who have previously received 2 lines of therapy; that is for patients who have a biopsy-proven diffuse large B-cell lymphoma, or those patients who have had an antecedent follicular lymphoma that has evolved into diffuse large B-cell lymphoma. This brings in another major player in this space. We’ve talked about how it’s an unmet medical need. Even if in the post-commercial setting, diffuse large B-cell lymphoma in the relapsed/refractory setting remains an unmet medical need, but at least we’re able to meet that need for certain patients. With both axi-cel and tisa-cel, there’s opportunities for patients to benefit and potentially enjoy long-term benefit.

Leo Gordon, MD: It is gratifying to see—and it goes back many years to the work, in Israel during the 1980s, of Carl June, Stan Riddell, and a variety of investigators—some of that basic CAR-T science work translate to the clinic. There were a number of trials that have been ongoing over the past several years, and I would say that the approval of 2 products, the Novartis Kymriah [tisa-cel], and the Kite Yescarta [axi-cel], have been a major advance for patients with diffuse large B-cell lymphoma. It allows treatment for patients who had previously very little hope. The response rates of these patients with refractory disease were very encouraging.

The ongoing study from Juno Therapeutics on liso-cel [lisocabtagene maraleucel], which is completing the cohort that’ll be submitted to the FDA likely sometime at the end of this year or the beginning of next year, is just about complete, and we would expect consideration for approval sometime in the early part of 2019. I think that’ll give us 3 good options for patients with relapsed/refractory diffuse large B-cell lymphoma.

Nilanjan Ghosh, MD, PhD: The TRANSCEND study is an active clinical trial testing liso-cel. In this study, the liso-cel, which is a composition of CD19 CAR-T cells containing CD4-positive and CD8-positive CAR-T cells, are being tested in relapsed/refractory diffuse large B-cell lymphoma, follicular lymphoma, and in high-grade B-cell lymphoma in the core cohort. The most recent update for the study was provided during the ASCO [American Society of Clinical Oncology] 2018 annual meeting: in this core cohort of patients—an 80% overall response rate and a 59% complete response rate were seen and reported.

In terms of adverse effects, the cytokine release syndrome, if you include all grades, was 37% and only 1 patient had grade 3/4 cytokine release syndrome. The neurotoxicity rate was 25% if you include all patients and only 15% of patients had grade 3/4 neurotoxicity. There were no deaths from cytokine release syndrome or neurotoxicity seen and reported in this core cohort group of patients.

Transcript Edited for Clarity 
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Transcript: 

Matthew Lunning, DO: Axi-cel is currently approved in those patients who have received greater than 2 lines of therapy and have biopsy-proven diffuse large B-cell lymphoma setting, primal mediastinal lymphoma, or those patients who have had an antecedent follicular lymphoma that is then evolved or transformed into diffuse large B-cell lymphoma.

Tisa-cel is similar in that it is approved for those patients who have relapsed/refractory diffuse large B-cell lymphoma who have previously received 2 lines of therapy; that is for patients who have a biopsy-proven diffuse large B-cell lymphoma, or those patients who have had an antecedent follicular lymphoma that has evolved into diffuse large B-cell lymphoma. This brings in another major player in this space. We’ve talked about how it’s an unmet medical need. Even if in the post-commercial setting, diffuse large B-cell lymphoma in the relapsed/refractory setting remains an unmet medical need, but at least we’re able to meet that need for certain patients. With both axi-cel and tisa-cel, there’s opportunities for patients to benefit and potentially enjoy long-term benefit.

Leo Gordon, MD: It is gratifying to see—and it goes back many years to the work, in Israel during the 1980s, of Carl June, Stan Riddell, and a variety of investigators—some of that basic CAR-T science work translate to the clinic. There were a number of trials that have been ongoing over the past several years, and I would say that the approval of 2 products, the Novartis Kymriah [tisa-cel], and the Kite Yescarta [axi-cel], have been a major advance for patients with diffuse large B-cell lymphoma. It allows treatment for patients who had previously very little hope. The response rates of these patients with refractory disease were very encouraging.

The ongoing study from Juno Therapeutics on liso-cel [lisocabtagene maraleucel], which is completing the cohort that’ll be submitted to the FDA likely sometime at the end of this year or the beginning of next year, is just about complete, and we would expect consideration for approval sometime in the early part of 2019. I think that’ll give us 3 good options for patients with relapsed/refractory diffuse large B-cell lymphoma.

Nilanjan Ghosh, MD, PhD: The TRANSCEND study is an active clinical trial testing liso-cel. In this study, the liso-cel, which is a composition of CD19 CAR-T cells containing CD4-positive and CD8-positive CAR-T cells, are being tested in relapsed/refractory diffuse large B-cell lymphoma, follicular lymphoma, and in high-grade B-cell lymphoma in the core cohort. The most recent update for the study was provided during the ASCO [American Society of Clinical Oncology] 2018 annual meeting: in this core cohort of patients—an 80% overall response rate and a 59% complete response rate were seen and reported.

In terms of adverse effects, the cytokine release syndrome, if you include all grades, was 37% and only 1 patient had grade 3/4 cytokine release syndrome. The neurotoxicity rate was 25% if you include all patients and only 15% of patients had grade 3/4 neurotoxicity. There were no deaths from cytokine release syndrome or neurotoxicity seen and reported in this core cohort group of patients.

Transcript Edited for Clarity 
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