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IMS 2026 | CEVOLUTION: cevostamab + pomalidomide and dexamethasone in multiple myeloma
Rakesh Popat, MBBS, MRCP, FRCPath, PhD, University College London Hospitals, London, UK, discusses the rationale for combining the FcRH5-targeted bispecific antibody cevostamab with pomalidomide and dexamethasone in the Phase III CEVOLUTION trial (NCT07555938). He highlights the high response rates observed with the combination in early studies and its potential role in earlier lines of treatment, while noting that the current trial excludes patients previously treated with BCMA- or GPRC5D-directed therapies. This interview took place at the 23rd International Myeloma Society (IMS) Annual Meeting in Glasgow, UK.
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Transcript
Cevostamab is a bispecific antibody targeting FcRH5, which is highly expressed on plasma cells. What we also find is that expression is not changed according to prior exposure to either CD38, monoclonal antibody, or importantly, a BCMA-targeted therapy. Now, this becomes important because BCMA-targeted therapies are increasingly being used at earlier lines of treatment, and there are ongoing clinical trials for first-line therapy...
Cevostamab is a bispecific antibody targeting FcRH5, which is highly expressed on plasma cells. What we also find is that expression is not changed according to prior exposure to either CD38, monoclonal antibody, or importantly, a BCMA-targeted therapy. Now, this becomes important because BCMA-targeted therapies are increasingly being used at earlier lines of treatment, and there are ongoing clinical trials for first-line therapy. And so, cevostamab as a bispecific antibody may well be used later on in a post-BCMA space. What we find with cevostamab is that it does have strong efficacy as monotherapy with response rates about 60 to 70%. But what we do find is that following a BCMA-targeted therapy, the response rate drops to just 10%. Once we combine it with pomalidomide, we start to see much higher response rates in the region of 80% and high MRD negativity rates. And hence, this is the CEVOLUTION clinical trial. CEVOLUTION is a phase three international clinical trial, which is randomizing patients who’ve had at least one prior line of therapy to receive cevostamab in combination with pomalidomide and dexamethasone or standard of care arm. And the primary endpoint will be progression-free survival, comparing the experimental arm with the control arms that we have available. The rationale is that you will be able to treat patients who’ve been previously exposed to other therapies. However, in this specific CEVOLUTION trial, we are excluding patients who’ve had prior BCMA or GPRC5D targeted therapies. But I believe in the future, it would be a valid option for patients who have been treated with those options in the past.
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