Updates in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma from ASH 2021 - Episode 3

How Will Bispecific Antibodies Fit Into the Multiple Myeloma Treatment Paradigm?

Amrita Y. Krishnan, MD, considers where bispecific antibodies will fit into the multiple myeloma treatment paradigms as single-agent or combination therapy.


Amrita Y. Krishnan, MD: We’re very excited about the results of teclistamab and talquetamab, the bispecific-targeting antibodies. Right now, they’re being studied in patients with very advanced myeloma who failed anti-CD38 antibodies, IMiDs [immunomodulatory drugs], and PIs [proteasome inhibitors]. Naturally, given these responses, given the tolerability of these drugs, there’s an interest in moving them earlier.

I could see them in the 1-to-3-relapse space. The question is would they be given as a single agent or in combination? Because we also have an ongoing study of daratumumab plus teclistamab, and daratumumab plus talquetamab. In that first-relapse setting, perhaps we would use daratumumab plus 1 of these bispecific antibodies to see if we can get similarly high response rates, depth of response, and long progression-free survival.

Overall, bispecific antibodies are going to be moved earlier into the course of disease, including in the frontline setting, either in combination in the frontline setting with daratumumab or possibly after a standard IMiD-PI induction and using the bispecific, for example, as a consolidation, perhaps instead of autologous stem cell transplant in the future. Ultimately, the bispecifics are going to be moved very early in the course of disease. We still don’t know, for example, if you had a BCMA-targeting agent, will you respond to BCMA CAR [chimeric antigen receptor] T cells. That’s where the question becomes, which bispecific do you use first? If you have concerns about that, perhaps people would look more to talquetamab, the GPRC5D-targeting agent, earlier and save BCMA targeting for CAR T vs teclistamab. But as the data emerge, that will also become more clear to us in terms of sequencing these agents.

ASH [American Society of Hematology Annual Meeting] 2021 showed us other new targets for myeloma. Among them was FcRH5 and a bispecific antibody, cevostamab, which was also studied in the phase 1 setting and presented by Suzanne Trudel on behalf of the study team. Similar to the other bispecifics, it used step-up dosing to reduce the risk of cytokine release. Similar to the other bispecifics, patients who were treated had extensive prior therapy and a median of 6 prior lines of therapy. Also interestingly, 13 patients in that study had prior bispecific antibodies, and 28 had had prior CAR T cells. We’re seeing patients treated with other T-cell engaging therapies first coming on to the cevostamab trial.

Overall, the drug appeared well tolerated. The usual expected adverse events, including hematologic toxicity and cytokine release, were in about 80% of patients. We saw a response rate of 56% at the target dose, including a third of the patients getting a very good partial response or better with responses deepening over time. Data are a little short in terms of the durability of responses, but the median duration of response is 11.5 months, which is certainly encouraging. The news for patients with myeloma is that we now have multiple targeting bispecific antibodies. Also, we’ve shown that you can move from 1 bispecific antibody to another bispecific antibody and still get responses.

Transcript edited for clarity.