Amrita Krishnan, MD, FACP, Talks Teclistamab for Patients With MM

Amrita Y. Krishnan, MD, FACP, director of the Judy and Bernard Briskin Center for Multiple Myeloma, City of Hope Cancer Center, Duarte, California, shares the results of a phase 3 trial of teclistamab, a BCMA bispecific T-cell engager, in relapsed/refractory multiple myeloma (MM); these data were presented at the virtual 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.


Hi. My name is Amrita Krishnan. I'm the director of the Judy and Bernard Briskin Center for Multiple Myeloma at the City of Hope Cancer Center in Duarte, California.

My abstract was about teclistamab, which is a BCMA bispecific T‑cell engager. The interest in this was due to the high expression of BCMA on myeloma cells, and the known activity of anti‑BCMA directed strategies with other classes of drugs such as antibody‑drug conjugates, as well as with cellular‑based therapies such as CAR T‑cells. We clearly know BCMA is a good target for myeloma.

The MAJESTIC 1 study was a phase I study that looked at patients who had measurable myeloma relapsed, or refractory, or intolerant to the established myeloma therapies. Part of the objectives of this study were obviously safety, tolerability, efficacy, and to identify the recommended phase II dosing.

What we saw in the study in this quite heavily pretreated population who had a median of 5 prior lines of therapy, I wouldn't say surprising, but certainly encouraging in terms of response rates being quite high in this heavily pretreated patient population, as well as expected safety and tolerability also was good.

We saw the expected side effects of cytokine release, which is, again, not unique to teclistamab, and is seen with any of these T‑cell engagers. Certainly, as this gets moved forward, it will be in terms of using this drug potentially earlier on in the course of patients’ therapy. Obviously right now, it's really to expand this recommended phase II dosing to a larger number of patients, to get more data in terms of efficacy and durability of responses.

Right now, we saw an overall response rate of 65 percent, which is certainly very encouraging, given how heavily pretreated these patients were. We need to see if that response rate certainly continues with the expansion cohorts.

The next step in this is to expand the recommended phase II dosing to a larger group of patients to, again, assess efficacy. Ultimately down the road it will be to study this agent in combination with other drugs, such as immunomodulatory agents certainly would be an attractive combination, also to explore its use earlier in the course of relapse. As I mentioned, the patients in this study had a median of 5 prior lines of therapy. Certainly, in earlier relapse potentially or even in the upfront setting, it would be attractive to explore this agent.

I think that this certainly cements the idea that the bispecific T‑cell engagers are an extremely active class of drugs in multiple myeloma. We don't have any that are yet FDA approved, but we have multiple agents with different targets, all in the phase I setting, that show incredible promise. As we move forward, we look to see a new armamentarium for us against myeloma.

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