IMW 2021 | Updates on immunotherapies for myeloma

Yeah, I think when we talk about immunotherapies, we’re talking about antibody-based strategies, as well as T-cell therapy directing strategy. So, within antibody-based strategies, we’re all familiar with the naked antibodies that target anti-CD38 or rather CD38 and SLAMF7. We’ve seen the clinical activity as monotherapy of daratumumab and isatuximab and dara has made its way to the frontline setting and those datasets are quite mature.

But now we are seeing more data with the antibody-drug conjugates. Over the past two years, we’ve seen belantamab mafodotin, which is the first BCMA-directed antibody-drug conjugate getting FDA approval based on the DREAMM-2 study, and now we have combination data with different scheduling and doses being developed. That’s really being done to mitigate some of the ocular side effects we were seeing with that strategy. It’s encouraging to see that even with lower doses and combining with proteasome inhibition and immunomodulatory drugs, those combinations retain their efficacy, especially with the pomalidomide combination in the ALGONQUIN study, we’re seeing better tolerability for patients. So, I think that there’s progress being made in understanding how to dose and schedule that antibody-drug conjugate better.

Then, talking about T-cell directing strategies, we have the bi-specific antibodies in that space. Most commonly, we’ve targeted BCMA. There are several constructs that are in the clinic. Teclistamab is probably the farthest ahead in terms of its clinical development, but all of them are showing clinical activity between 60 to 80, 85% in terms of overall response rates, but lower CRS and neurotoxicity percentage in grading compared to the CAR T-cell therapies. That’s the T-cell directed strategy that has shown the most efficacy, whether it’s ide-cel or cilta-cel. Now both those CAR-Ts are moving into the earlier line setting and even being evaluated for high-risk patients in the frontline setting.

So, I think the future belongs to immunotherapies. We’ve come from naked antibodies going towards the antibody-drug conjugate combinations, and there’ll be room for each of these strategies. Bi-specifics and CAR-Ts are probably the more promising T-cell directing therapies. In one of the talks earlier today from my colleague Vincent Rajkumar, he showed a figure where we have seven or eight other surface molecule targets that are being explored in preclinical as well as clinical space. So, I’m very hopeful that all these immunotherapies eventually lead to curability for majority of myeloma patients.