Cevostamab Combo Shows Enduring Responses in R/R Multiple Myeloma

"Cevostamab plus pomalidomide/dexamethasone induced deep and durable responses in BCMA-[directed therapy]–naive patients," according to study author Hira S. Mian, MD, MSc, FRCPC.

High response rates and a manageable safety profile were observed among patients with BCMA therapy–naive relapsed/refractory multiple myeloma who received cevostamab (RG6160, BFCR4350A) plus pomalidomide (Pomalyst) and dexamethasone, according to a presentation on dose-expansion findings from the phase 1 CAMMA 1 trial (NCT04910568) at the 22nd Annual International Myeloma Society Meeting and Exposition.1

Among patients who received cevostamab at a target dose of 70 mg (n = 29) at a median time on study of 10.4 months (95% CI, 6.3-15.5), all experienced adverse effects (AEs). The rates of grade 3/4 AEs and serious AEs were 89.7% and 55.2%, respectively. No patients had grade 5 AEs. AEs leading to discontinuation of cevostamab and pomalidomide occurred in 3.4% and 20.7% of patients, respectively; no AEs led to discontinuation of dexamethasone.

Among patients who received cevostamab at a target dose of 105 mg (n = 25), at a median time on study of 8.3 months (95% CI, 3.3-15.7), all experienced AEs. The rates of grade 3/4 AEs and serious AEs were 96.0% and 60.0%, respectively. One patient had a grade 5 AE. AEs leading to discontinuation of cevostamab pomalidomide, and dexamethasone occurred in 4.0%, 24.0%, and 8.0% of patients, respectively.

AEs of interest across both cohorts included neutropenia, anemia, thrombocytopenia, cytokine release syndrome (CRS), infections, and rash.

For patients in the 70-mg cohort, the overall response rate (ORR) was 86.2% (95% CI, 71.9%-100%). The rates of stringent complete response (sCR), CR, very good partial response (VGPR), and PR were 34.5%, 10.3%, 27.6%, and 13.8%, respectively. Patients in the 105-mg cohort achieved an ORR of 88.0% (95% CI, 73.3%-100%). The rates of sCR, CR, VGPR, and PR were 36.0%, 12.0%, 28.0%, and 12.0%, respectively.

“Cevostamab plus pomalidomide/dexamethasone induced deep and durable responses in BCMA[-directed therapy–]naive patients,” Hira S. Mian, MD, MSc, FRCPC, said during the presentation.

Mian is an associate professor of oncology in the Faculty of Health Sciences at McMaster University in Hamilton, Ontario, Canada.

What Was the Rationale for Investigating Cevostamab in Multiple Myeloma?

FcRH5 is expressed exclusively in B-cell lineage and ubiquitously on multiple myeloma cells. It is expressed independent of BCMA expression, making it an attractive therapeutic target for multiple myeloma, Mian noted. Phase 1 trial (NCT03275103) data with cevostamab monotherapy in patients with later-line multiple myeloma showed that the agent had a manageable safety profile and induced deep and durable responses, which were particularly pronounced in patients naive to BCMA-directed therapy.

What Was the Design of the Dose-Expansion Portion of the CAMMA 1 Study?

CAMMA 1 enrolled patients with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy, including an immunomodulatory drug and a proteasome inhibitor. Patients with pomalidomide-refractory disease were excluded.

In the initial dose-expansion cohort—arm B1E—patients were randomly assigned to receive a target dose of intravenous (IV) cevostamab at either 70 mg or 105 mg on days 1 and 15 of each 28-day cycle, oral pomalidomide at 2 mg on days 1 to 21 of each cycle, and IV or oral dexamethasone at 20 mg on days 1, 8, 15, and 22 of each cycle. In the 14-day pre-phase portion, patients received cevostamab at a double step-up dosing regimen of 0.3 mg on day 1 and 3.3 mg on days 2 to 4, followed by the target dose on day 8; during this portion, patients also received dexamethasone on days 1 to 4 and day 8.

In the subsequent expansion cohort—arm B3E— during the 21-day pre-phase portion, cevostamab was initiated with triple step-up dosing at 0.3 mg on day 1, 1.2 mg on days 2 to 4, and 3.6 mg on day 8, followed by the target dose on days 9 to 11; during this portion, patients also received dexamethasone on days 1 to 4 and days 8 to 11. Following the pre-phase portion, patients were treated with the combination at the same dose and schedule as in the B1E expansion cohort.

The primary end points were safety and tolerability, as well as the identification of the recommended phase 2 dose. Secondary end points included pharmacokinetics, pharmacodynamics, and antitumor activity.

Notably, data from the arm B safety run-in stage of CAMMA 1, which were presented at the 20th Annual IMS Meeting and Exposition, showed that at a data cutoff of August 21, 2023, the triplet regimen was associated with manageable toxicities and led to generally durable responses that deepened over time in 8 evaluable patients.2

What Were the Baseline Characteristics of Patients Enrolled in the Dose-Expansion Portion of the CAMMA 1 Study?

Among patients in the dose-expansion stage who received cevostamab at 70 mg, the median age was 65 years (range, 40-76), the median number of prior lines of therapy was 2 (range, 1-6), 72.4% of patients were triple-class exposed, and 72.4% of patients were refractory to their last line of therapy.1 Among patients who received cevostamab at 105 mg, the median age was 65 years (range, 48-80), the median number of prior lines of therapy was 2 (range, 1-6), 56.0% of patients were triple-class exposed, and 68.0% of patients were refractory to their last line of therapy.

What Were the Infection Rates in the Dose-Expansion Portion of CAMMA 1?

In the 70-mg cohort, infections occurred in 65.5% of patients. These included upper respiratory tract infection (URTI; 27.6%), pneumonia (10.3%), COVID-19 (10.3%), urinary tract infection (UTI; 6.9%), and rhinitis (10.3%). Grade 3/4 and serious infections occurred in 13.8% and 17.2% of patients, respectively. Immunoglobulin administration was required in 62.1% of patients.

In the 105-mg cohort, infections occurred in 72.0% of patients. These included URTI (16.0%), pneumonia (16.0%), COVID-19 (8.0%), and UTI (12.0%). Grade 3/4 and serious infections occurred in 28.0% and 36.0% of patients, respectively. Immunoglobulin administration was required in 68.0% of patients. No patients in either cohort experienced grade 5 infections or infections leading to discontinuation of any study drug.

What Were the CRS Rates in the Dose-Expansion Portion of CAMMA 1?

Among patients treated with double step-up dosing (n = 28), any-grade, grade 2 or higher, and grade 3 or higher CRS was reported in 78.6%, 21.4%, and 3.6% of patients, respectively. In total, 35.7%, 42.9%, and 21.4% of patients received tocilizumab (Actemra), corticosteroids, or tocilizumab and corticosteroids for CRS, respectively.

Patients treated with triple step-up dosing (n = 26) had notably lower levels of grade 2 or higher CRS and tocilizumab use. Any-grade, grade 2 or higher, and grade 3 or higher CRS was reported in 53.8%, 7.7%, and 0% of patients, respectively. In total, 7.7%, 3.8%, and 3.8% of patients received tocilizumab, corticosteroids, or tocilizumab and corticosteroids for CRS, respectively

“Triple step-up dosing appears to provide [an] optimal CRS mitigation [strategy],” Mian noted.

What Were the Additional Findings From the Dose-Expansion Portion of CAMMA 1?

Among minimal residual disease (MRD)–evaluable patients in the double step-up dosing cohort who were treated with cevostamab at a target dose of 70 mg (n = 15), 46.7% (95% CI, 21.4%-71.9%) achieved an MRD-negative CR or better at any time; the median time on study in this population was 13.6 months (range, 10.4-15.5). Among MRD-evaluable patients in the double step-up dosing cohort who were treated with cevostamab at a target dose of 105 mg (n = 13), 38.5% (95% CI, 12.0%-64.9%) achieved an MRD-negative CR or better at any time; the median time on study in this population was 12.5 months (range, 3.3-15.7).

Furthermore, an analysis of response evolution stratified by target dose level showed that responses deepened over time at both target dose levels.

“CAMMA 1 is an ongoing study, with additional time on study needed to confirm both the depth and durability of responses, particularly in that triple step-up dosing [cohort],” Mian concluded.

Disclosures: Mian reported advisory board participation/receiving honoraria from AbbVie, BMS, GSK, Janssen, Pfizer, Roche, and Sanofi; as well as receiving institutional research funding from Pfizer.

References

1. Mian HS, Riley CH, Popat R, et al. Cevostamab plus pomalidomide (pom) and dexamethasone (dex) in relapsed/refractory multiple myeloma (RRMM): phase I dose-expansion results from the CAMMA 1 study. Presented at: 22nd Annual International Myeloma Society Meeting and Exposition; September 17-20, 2025; Toronto, Canada. Abstract OA-14.
2. Jelinek R, Spencer A, Krishnan A, et al. Novel combination immunotherapy for relapsed/refractory multiple myeloma: initial phase I safety run-in results for cevostamab in combination with pomalidomide and dexamethasone. Presented at the 20th Annual International Myeloma Society Meeting and Exposition; September 27,30, 2023; Athens, Greece. Abstract P-019.