Academic Focus: CAR-T Therapy for Relapsed/Refractory NHL - Episode 4
<iframe width="560" height="315" src="https://www.youtube.com/embed/9tcqFKRlN0M?rel=0&autoplay=1&fs=0" frameborder="0" allow="accelerometer; autoplay; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe>Transcript: Nilanjan Ghosh, MD: The ZUMA-1 study was in patients with refractory diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma. This was a study which enrolled 111 patients, of which 101 received axi-cel [axicabtagene ciloleucel] treatment. Axi-cel is a CAR T-cell product from Kite Pharma. The patients on the study were heavily pretreated, and they had failed at least 2 prior lines of therapy. The overall response rate for patients in the study was 82%, of which 58% achieved a complete response. Some patients had a partial response initially and then converted into a complete response with a longer follow-up. In terms of toxicity in this study, 94% of patients had CRS [cytokine release syndrome], if you include all grades, of which 13% had grade 3/4 CRS. In terms of neurotoxicity, 64% of patients had neurotoxicity if you include all grades, and 28% had neurotoxicity of grade 3 and 4.
Actemra [tocilizumab] and dexamethasone were used for treatment of CRS and neurotoxicity. The use of these agents did not have any adverse effects on the efficacy. There were 3 deaths from toxicity in the study.
Matthew Lunning, DO: The JULIET trial is a very interesting trial. It led to the FDA approval of tisa-cel [tisagenlecleucel], but we haven’t yet seen it in the peer-reviewed manuscript. One of the things about the JULIET trial is that we’ve seen the publications, presentations and abstracts from the American Society of Hematology, and we’ve read the data from the European Hematology Association, all of which were very promising: it allowed for FDA approval in the relapsed/refractory diffuse large B-cell lymphoma setting.
When the United States’ prescribing information was released, there were several patients removed from the clinical trial due to either not having restaging imaging prior to CAR T-cell therapy, or no evidence of disease at the time of infusion of CAR T-cell therapy, which was the majority of those patients. In that setting there were still patients who had achieved remission—one of the important concepts we’re learning with tisa-cel, axi-cel and liso-cel [lisocabtagene maraleucel] is that, if you can achieve a complete remission, they may be durable.
There were data demonstrated with tisa-cel showing they were, in patients who had achieved a partial remission, able to convert to complete remission. You have to be conscientious of those patients who are in a partial remission because their next event may be progression.
Leo Gordon, MD: When one looks at responses in this heavily pretreated group of patients, the standard approach that we had prior to CAR-T was summarized very nicely in the SCHOLAR-1 study, suggesting that long-term responses and remissions occurred in maybe 5% to 10% of patients. Most patients had progressed and died of their disease within less than a year after treatment. But what we’re seeing with this CAR-T approach is an overall response rate of about 80%, and a complete response rate in the range of about 50% and 55%, with long-term durability—and that’s measured in about 2 years because that’s how long these studies have been going on. Long-term responses in the range of somewhere between 48% and 52% of patients are experienced, and that’s been mostly on the Juno Therapeutics trial with liso-cel. That is what we’re seeing in about 50% of patients with previously dismal hopes of treatment: disease-free states with normal performance status, coming in for routine follow-up. We’re very excited about these results.
The published data from the ZUMA-1 trial also suggest the response rate is in the low 80% range with complete responses around 50% to 54%. It’s interesting to see the data from all 3 studies; from the TRANSCEND study from Juno, the KITE study, and JULIET study from Novartis, all of which exhibited very similar responses of around 80%, complete responses around 50%, and long-term survival, free of disease, somewhere south of 50%.
Transcript Edited for Clarity