Select Topic:
Browse by Series:

CAR T Treatment as New Salvage Therapy & TRANSCEND Study

Insights From: Nilanjan Ghosh, MD, PhD, Levin Cancer Institute; David Maloney, MD, PhD Fred Hutchinson Cancer Research Center
Published: Wednesday, Nov 28, 2018



Transcript: 

Nilanjan Ghosh, MD, PhD: The FDA-approved indication for axicabtagene ciloleucel is in relapsed and refractory diffuse large B-cell lymphoma. Diffuse large B-cell lymphoma materializes out of follicular lymphoma and in primary mediastinal B-cell lymphoma. This is after failure of 2 prior lines of therapy. The approval for CTL019 [Kymriah] is in relapsed and refractory diffuse large B-cell lymphoma and also in transformed follicular lymphoma. This is also after failure of 2 prior lines of therapy.

Relapsed and refractory diffuse large B-cell lymphoma transformed from follicular lymphoma or primary mediastinal B-cell lymphoma tends to have very poor outcomes. There was a study called the SCHOLAR-1 study, which was published a few years ago, that looked at this population of patients who had failed at least 2 prior therapies and found the outcomes to be very poor in this group of patients. The overall response rate was about 26%. The complete responses were very less, about 7% or so, and the median survival was only 6 months. That tells us how poorly these patients can do. This population of patients was then selected for testing for this new therapy, called CAR T therapy.

The design of the trial testing lisocabtagene maraleucel [liso-cel] is called the TRANSCEND study from Juno Therapeutics. The population of patients who are being tested have relapsed and refractory diffuse large B-cell lymphoma, transformed follicular lymphoma, or high-grade B-cell lymphoma [HBCL], which includes double-hit and triple-hit lymphoma after failure of at least 2 prior therapies. This is in the core cohort of the study. Once the patient is deemed eligible, they are set up for apheresis when the cell product is collected and then sent to Juno Therapeutics for generation of the CAR T cells, which also includes the separation of the T cells into CD4 and CD8 groups, which are then separately expanded and have 2 separate products ready at the end, which are then given to the patient.

While the patient is waiting, a bridging therapy is allowed. Based on the clinical need and investigator discretion, bridging treatment can be given to these patients. If bridging treatment is given, a repeat scan is performed prior to lymphodepleting chemotherapy to make sure we get curative assessment prior to starting lymphodepleting. Lymphodepleting therapy is given with fludarabine [Imbruvica] and cyclophosphamide [Cytoxan] for 3 days. The CAR T cell product can be given between 2 and 7 days after completion of lymphodepletion. The CD8-positive CAR T cells and the CD4-positive CAR T cells are given in 1:1 composition to the patient, who is then observed for toxicity and management post completion of this infusion.

We know that relapsed and refractory diffuse large B-cell lymphoma is an area of clinical unmet need. Knowing that the CAR T therapies have been approved and clinical trials are available for CAR T therapies, we have seen a tremendous demand for these therapies at our center. We see a lot of patients who are referred from providers, as well as many patients who have been directly calling to see if they’re eligible for CAR T therapies or not.

Transcript Edited for Clarity 
Slider Left
Slider Right


Transcript: 

Nilanjan Ghosh, MD, PhD: The FDA-approved indication for axicabtagene ciloleucel is in relapsed and refractory diffuse large B-cell lymphoma. Diffuse large B-cell lymphoma materializes out of follicular lymphoma and in primary mediastinal B-cell lymphoma. This is after failure of 2 prior lines of therapy. The approval for CTL019 [Kymriah] is in relapsed and refractory diffuse large B-cell lymphoma and also in transformed follicular lymphoma. This is also after failure of 2 prior lines of therapy.

Relapsed and refractory diffuse large B-cell lymphoma transformed from follicular lymphoma or primary mediastinal B-cell lymphoma tends to have very poor outcomes. There was a study called the SCHOLAR-1 study, which was published a few years ago, that looked at this population of patients who had failed at least 2 prior therapies and found the outcomes to be very poor in this group of patients. The overall response rate was about 26%. The complete responses were very less, about 7% or so, and the median survival was only 6 months. That tells us how poorly these patients can do. This population of patients was then selected for testing for this new therapy, called CAR T therapy.

The design of the trial testing lisocabtagene maraleucel [liso-cel] is called the TRANSCEND study from Juno Therapeutics. The population of patients who are being tested have relapsed and refractory diffuse large B-cell lymphoma, transformed follicular lymphoma, or high-grade B-cell lymphoma [HBCL], which includes double-hit and triple-hit lymphoma after failure of at least 2 prior therapies. This is in the core cohort of the study. Once the patient is deemed eligible, they are set up for apheresis when the cell product is collected and then sent to Juno Therapeutics for generation of the CAR T cells, which also includes the separation of the T cells into CD4 and CD8 groups, which are then separately expanded and have 2 separate products ready at the end, which are then given to the patient.

While the patient is waiting, a bridging therapy is allowed. Based on the clinical need and investigator discretion, bridging treatment can be given to these patients. If bridging treatment is given, a repeat scan is performed prior to lymphodepleting chemotherapy to make sure we get curative assessment prior to starting lymphodepleting. Lymphodepleting therapy is given with fludarabine [Imbruvica] and cyclophosphamide [Cytoxan] for 3 days. The CAR T cell product can be given between 2 and 7 days after completion of lymphodepletion. The CD8-positive CAR T cells and the CD4-positive CAR T cells are given in 1:1 composition to the patient, who is then observed for toxicity and management post completion of this infusion.

We know that relapsed and refractory diffuse large B-cell lymphoma is an area of clinical unmet need. Knowing that the CAR T therapies have been approved and clinical trials are available for CAR T therapies, we have seen a tremendous demand for these therapies at our center. We see a lot of patients who are referred from providers, as well as many patients who have been directly calling to see if they’re eligible for CAR T therapies or not.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Rapid Reviews in Oncology®: Practice-Changing Data in Acute Myeloid Leukemia: A Rapid Update From Atlanta OnlineDec 21, 20182.0
Community Practice Connections™: 2nd Annual European Congress on Hematology™: Focus on Lymphoid MalignanciesDec 30, 20182.0
Publication Bottom Border
Border Publication
x