Dr Kumar on Efficacy and Safety Data With Cevostamab-Based Regimens in R/R Myeloma

"[Cevostamab is] effective when used in combination regimens, and [in the 105-mg arm, 38.5%] of patients got to an MRD-negative state. The responses were durable in this patient population."

Shaji Kumar, MD, leader of Cancer Risk Assessment in the Early Detection and Interception Research Program, a consultant and research chair in the Division of Hematology in the Department of Internal Medicine, and a professor of medicine at the Mayo Clinic Comprehensive Cancer Center, expanded on key efficacy, safety, and biomarker data from the phase 1b CAMMA 1 trial (NCT04910568), which evaluated cevostamab (BFCR4350A) alone or in combination with pomalidomide (Pomalyst) and dexamethasone in patients with relapsed/refractory multiple myeloma.

In the dose-expansion portion of CAMMA 1, cevostamab plus pomalidomide and dexamethasone produced an overall response rate (ORR) of 86.2% (95% CI, 71.9%-100%) in patients who received cevostamab at 70 mg (n = 29) and 88.0% (95% CI, 73.3%-100%) among those who received the agent at 105 mg (n = 25). Kumar noted that these figures represent a notable improvement over the approximate 60% ORR previously observed with single-agent cevostamab. Furthermore, deep responses were achieved; the rates of minimal residual disease (MRD)–negative complete response or better at any time were 46.7%(95% CI, 21.4%-71.9%) and 38.5% (95% CI, 12.0%-64.9%) in the 70-mg arm and 105-mg arm, respectively. Biomarker analyses confirmed these clinical findings, showing that both doses generated rapid and durable decreases in serum BCMA levels, consistent with effective tumor reduction

Regarding safety, investigators found that infections were the most commonly observed toxicity, as expected with bispecific antibodies, Kumar said. However, the rate of grade 3 and 4 adverse effects was somewhat lower than what has been observed with other agents in this class, he noted. Importantly, there were no treatment-related deaths reported in the study. To mitigate common toxicities such as cytokine release syndrome (CRS), the trial utilized double and triple step-up dosing strategies. In particular, the triple step-up dosing approach used in 26 patients successfully decreased the rates of CRS, Kumar stated. Investigators hope that continued follow-up will provide further clarity on the long-term benefits of this regimen in the relapsed/refractory setting, he concluded.