IMS 2026 | CAMMA 1: fixed-duration cevostamab shows durable responses in R/R multiple myeloma

The CAMMA 1 Arm A results were presented at the IMS meeting on behalf of my colleagues. And this is a trial that is looking at Cevostamab, a novel FcRH5 bispecific antibody. This has been reported previously and published in a phase one monotherapy study employing single and double and triple step-up dosing and Q3-week dosing thereafter at 160 milligram dose target level. The CAMMA 1 study, which was initiated in 201, was evaluating the safety and activity of fixed duration modified regimen given initially Q week for two months, Q2 four weeks for four months, and then Q4 weeks thereafter. Patients with relapsed refractory multiple myeloma who had no established therapy were enrolled with an ECOG performance status of zero or one. The median age of the patients was about 65 odd years of age, about a third had high-risk cytogenetics, about a little less than 10% had extramedullary disease. Patients had had a median of four prior lines of therapy, and these patients were triple-class refractory in about two-thirds and refractory to their last line of therapy in about 85% to 86% of cases, roughly. The drug was safe. There were, obviously, with any bispecific antibody AEs, grade 3-4 AEs occurred in 70% of cases. There were two deaths in the study, one due to sepsis and one due to a cardiovascular event. And there were two patients who had to discontinue one account of a pneumonia and one who developed hemophagocytic syndrome and AML. The side effect profile showed neutropenia to be in about over half the patients. CRS was seen in three-fourths of the patients. Infections were seen in three-fourths of the patient. And there were some rashes, but no substantial other skin, hair, or nail toxicity was seen. And only one case of ICANS was observed. So it was felt that this regimen was well tolerated. The infections certainly are always a talking point for bispecifics and in in this case, the grade 3-4 infection rate, once episodic, once IgG supplementation was implemented, was manageable. The patients in this trial did get tocilizumab in about a third, steroids in about 16%, and both steroids and tocilizumab in about 16%. But the regimen was well-tolerated with a single step-up dose employed, with the target dose studied in this being 90 mg after a 3.6 milligram step-up dose. What we know as far as efficacy goes is about 70% of patients responded. Of the 24 patients that were enrolled on the study, eight achieved a complete remission and and four of these were MRD-evaluable. All were MRD-negative at the 10 to minus 6 level. The median duration of response for patients in partial response was 46.5 months, and median duration of CR was 46.5 months, with a 36-month duration of response in 100%. And this needs to be kept in perspective was with a fixed duration regimen given for 13 cycles. So this is something that we see as a unique trial so far. Very few bispecifics have been reported that%. To summarize, this fixed duration, which has to be emphasized, modified regimen with Q2 week dosing in the beginning had a manageable safety profile. There were low rates of grade 3, 4 infection, only about a third, though episodic IgG supplementation was implemented. And as I stated before, once you give regular IgG supplementation as we do with bispecifics, this is likely to fall further. This fixed duration modified regimen did achieve deep responses and the responses continued after completion of about 12 months of treatment with 9 out of 11 patients who achieved a partial response or better maintaining their response for more than 40 months. So this is certainly a very exciting data.

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