ASH 2024 | The impact of prior exposure to belantamab on outcomes with ide-cel in multiple myeloma

The BCMA or B-cell maturation antigen has emerged as a promising target for anti-myeloma therapies. There are various different ways in which we can target BCMA in multiple myeloma. One is antibody-drug conjugate, mainly belantamab. The BiTE therapy, which is T-cell engager, bispecific T-cell engager like teclistamab or CAR T-cell therapy like ide-cel. Belantamab, which was approved in 2021, had to be taken off the market after it failed to show superiority. But recently, the two trials, DREAMM-6 and DREAMM-7, are suggesting that the belantamab may make a comeback. Also, a lot of CAR T-cell, BCMA CAR T-cell therapy trials have excluded patients with prior anti-BCMA exposure. So we don’t really know what happens if the patient had received belantamab in the past and now they are getting CAR T-cell therapy. So in this study, what we wanted to see was if prior exposure to belantamab, which is an ADC against BCMA, has any impact on the outcomes with BCMA CAR T-cell therapy. And we specifically chose ide-cel because that was the most frequently used BCMA-CAR T-cell therapy in our center. We identified all the patients who got BCMA-CAR T-cell therapy in our center and looked at how many of them had prior exposure to belantamab. We tried to compare the outcomes in patients with prior exposure to belantamab versus those who did not have prior exposure to belantamab. We identified that out of 61 patients who received ide-cel therapy, 22 had prior exposure to belantamab, and 39 patients did not have prior exposure to belantamab. So we saw what the safety and efficacy outcomes were in each group. So coming to the safety aspect, the BCMA CAR T-cell therapy or the ide-cel was equally safe in both the groups. So prior exposure to belantamab did not influence any safety outcomes. But the efficacy outcomes were different. Patients who had prior exposure to belantamab had inferior efficacy outcomes with ide-cel therapy. Specifically, the PFS and progression-free survival and overall survival were significantly inferior in patients who had prior exposure to belantamab, which is expected that if someone is already being exposed to BCMA therapy in the past, they would have inferior outcomes with subsequent BCMA therapies. But what was more interesting in our study was that patients who responded to BCMA CAR T-cell therapy, when we look back, they had not responded to BCMA ADC, that is belantamab. And the opposite was true as well. If they did not respond to CAR T-cell therapy, they had a higher chance that they had responded to BCMA ADC. So this was interesting because this shows how a same antigen, BCMA antigen, responds very differently to different forms of therapy against it. We don’t really understand why this happened. When we reviewed the literature, there is some data showing the same thing. There was a study published by Cohen et al. where they looked at outcomes with cilta-cel in patients with prior exposure to BCMA ADC and BCMA BiTE. They also found the same thing, that patients who responded to CAR-T had not responded to other anti-BCMA therapies, and patients who did not respond to CAR-T had responded to some prior anti-BCMA therapy. So what we need to now find out is what factors influence which patient would respond to which form of anti-BCMA therapy so that we can use the best anti-BCMA therapy for a given patient. And this will also help us in deciding what the subsequent lines of therapy should be.

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