EHA 2021 | Brexucabtagene autoleucel vs SOC for R/R MCL
Georg Hess, MD, University Medical Center Mainz, Mainz, Germany, discusses how treatment of patients with R/R (relapsed/refractory) mantle cell lymphoma (MCL) previously treated with Bruton’s tyrosine kinase (BTK) inhibitors with brexucabtagene autoleucel compares to treatment with standard of care (SOC). The clinical efficacy of brexucabtagene autoleucel in patients with R/R MCL was established during the ZUMA-2 trial (NCT02601313) and data on the effectiveness of SOC across Europe was collected in SCHOLAR-2. After a median duration of 27.6 months from the initiation of SOC in SCHOLAR-2, the median overall survival (OS) was 15.7 months, and after 15 months the OS rate was 52%. A naïve, unweighted comparison showed brexucabtagene autoleucel to be superior, with an OS HR of 0.37. Consistent results were seen with the IPW approach. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.
Transcript (edited for clarity)
KTE-X19 coming from the ZUMA-2 trial has raised tremendous attention over the last two years. When Michael Wang for the first time presented the data at ASH 2019, it was really a rumor in the room when he could demonstrate that multiply relapsed mantle cell lymphoma patients benefited that intensively from a CAR-T treatment. Overall response was more than 80% and it was not only the overall response rate, but it was especially the duration of response, which even with further follow-up showed that there is roughly one and a half year PFS now in these patients...
KTE-X19 coming from the ZUMA-2 trial has raised tremendous attention over the last two years. When Michael Wang for the first time presented the data at ASH 2019, it was really a rumor in the room when he could demonstrate that multiply relapsed mantle cell lymphoma patients benefited that intensively from a CAR-T treatment. Overall response was more than 80% and it was not only the overall response rate, but it was especially the duration of response, which even with further follow-up showed that there is roughly one and a half year PFS now in these patients.
And you have to keep in mind which population of patients was treated. It was patients with at least three prior lines, and they had to be refractory intolerant to BTK inhibitor. That is kind of the core question today, what do we do with these patients? And in general, life expectancy of these patients is roughly six months. And so, everybody was very impressed, but one of the key issues is that this is a single arm trial, so nobody really does know how this compares to another type of treatment.
And so the SCHOLAR-2 was an approach to do that on a chart review basis. What we basically did is to identify patients with the same characteristics like those being enrolled in ZUMA-2, that means refractory to a BTK inhibitor and not being treated with a CAR T-cell like KTE-X19. And then the results of these patients in ZUMA-2 were compared to these patients we identified from our real-world scenario. And so, it was roughly 60 patients in both of these cohorts, and they were well-balanced. Now it’s difficult to find these patients so it was an international efforts to do so, but indeed so we had quite a good compared group of patients in each arm. And then there was adjustment for statistic parameters. And then if you take it down after all these adjustments, which have been recommended by authorities, indeed you can show that there is a dramatic difference in between overall survival for the ZUMA-2 patients compared to standard of care patients. And as expected, the overall survival for patients with standard of care was less than one year. Whereas it has not been reached for patients in the ZUMA-2 trial.
So, I mean, this is not a Phase III randomized trial, but it’s difficult to do these trials these days and so I think it’s an helpful instrument to understand how substantially start data really are. And so, with after scoring and propensity adjustments, I think this is as good as it can be at this time and it’s helpful to really understand the value of this approach and to my understanding it underlines that CAR T-cell treatment after BTK failure in mantle cell lymphoma patients is probably the most promising option we have today for our patients.
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