Fixed-Duration Cevostamab Yields Durable Responses Off Therapy

The phase 1 GO39775 trial (NCT03275103) evaluated cevostamab, a first-in-class FcRH5/CD3 bispecific antibody, as fixed-duration therapy. Investigators administered cevostamab every 3 weeks for 17 cycles, rather than as continuous treatment, in patients with relapsed or refractory multiple myeloma.

Lead study author Adam D. Cohen, MD, director of Myeloma Immunotherapy and professor of medicine at the Hospital of the University of Pennsylvania, spoke with CancerNetwork^® about the rationale behind capping treatment duration and what happened to patients who stopped therapy in response. Cohen described a subset of patients who were able to sustain their responses for several months after stopping therapy, which included 1 patient in remission 4 years out from treatment.

Transcript:

CancerNetwork: What was the clinical rationale for capping treatment with cevostamab, and what did the data show about patients maintaining responses off therapy?

At the time this study was designed, in 2017, this was a novel or radical idea. Almost all the trials, especially in late-line relapsed/refractory myeloma, gave continuous therapy. Once patients started treatment, they continued indefinitely unless they progressed or had unacceptable toxicity, and that includes the currently available bispecific antibodies that target BCMA or GPRC5D. What we have learned, subsequently, is that continuous therapy might not be the best approach, particularly for T-cell–engaging therapy. If you continuously activate T cells over and over again indefinitely, that may lead to T-cell dysfunction over time. It certainly seemed to increase the risk of infections, particularly with the BCMA-targeted bispecifics, where you see profound hypogammaglobulinemia and perhaps ongoing T-cell dysfunction.

The rationale was: what if we treat for a fixed duration? In this trial, that was 17 cycles, with the drug given every 3 weeks, so about 51 weeks, or roughly 1 year of treatment. The thought was that if patients were in a good response, you could stop treatment, which might allow recovery of their endogenous immunity and a lower long-term infection risk. It might also lower the risk of antigen escape because you are not keeping constant pressure on the FcRH5 target, potentially meaning fewer patients relapsing with FcRH5-low or -negative disease. That was the rationale at the time. It turned out to be prescient because fixed-duration treatment is now becoming something of a [trend] in [multiple] myeloma therapy. There is this push to try to do more fixed-duration treatments based on some of these same findings with continuous dosing.

In terms of what the data showed for patients who completed all 17 cycles and ended in a response, there were about 26 such patients, and 17 of them were still in an ongoing response at the time of data cutoff. That includes several patients with more than 30 months of ongoing remission; I have one patient who is 4 years out now without any other therapy and still in remission. For a subset of patients, particularly those with the deepest responses—complete responders especially—you may be able to stop therapy. That is what I think this trial helped teach us.

Reference

Cohen AD, Richter J, Trudel S, et al. FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial. Nat Med. Published online July 22, 2026. doi:10.1038/s41591-026-04522-3