Comparing Different Monoclonal Antibodies Within a Treatment Strategy for Patients with Multiple Myeloma

A meta-analysis, conducted by Wu Ye and collaborators from the Department of Hematology at the West China Hospital, Sichuan University in Sichuan Province, China, evaluated monoclonal antibodies (MAbs) with three different targets when used in combination with bortezomib or immunomodulators and dexamethasone/prednisone in the treatment of patients with multiple myeloma (MM).

Published in BMC Cancer, their report relayed that patients treated with MAbs targeting CD38 had longer progression-free survival (PFS) and better treatment response than patients in the SLAMF7 or PD-1/PD-L1 groups. The SLAMF7-directed treatment, though not as effective as the CD38 MAbs, was associated with the lowest incidence of grade III or higher neutropenia. MAbs targeting PD-1/PD-L1 performed the worst, and the researchers recommend against their use in patients with MM.

The study included 5,367 patients from 11 randomized controlled trials that used at least one of the indicated MABs. They reported hazard ratios (HRs) for overall survival (OS) and PFS, grade III or higher adverse events, as well as relative risk (RR) for overall response rate, complete response (CR) or better, very good partial response (VGPR) or better, VGPR, partial response, and stable disease among the three groups.

The study authors calculated the HRs for PFS between the following MAb target groups:

  • CD38 versus SLAMF7: 0.662 (95% CI, 0.543–0.806)
  • CD38 versus PD-1/PD-L1: 0.317 (95% CI, 0.221–0.454)
  • SLAMF7 versus PD-1/PD-L1: 0.479 (95% CI, 0.328–0.699)

Additionally, the HR for OS of the CD38 group versus the SLAMF7 group was 0.812 (95% CI, 0.584–1.127), the RR for CR or better of CD38 versus SLAMF7 was 2.253 (95% CI, 1.284–3.955), and the RR for neutropenia of CD38 vs SLAMF7 was 1.818 (95% CI, 1.41–2.344).

The analysis was limited in that the number of studies testing SLAMF7 and PD-1/PD-L1-specific MABs was too small to draw conclusions from, and pooled RRs for treatment response relative to controls between the included studies were heterogenous. Additionally, the authors stated that original, individual patient data would have been more valuable than the abstracted data used for analysis.

 

According to the authors, this is the first analysis of different MABs when combined with other agents in the treatment of patients with MM. In general, the MAbs targeting CD38 in combination with bortezomib/immunomodulators plus dexamethasone/prednisone showed significant therapeutic value—though MAbs targeting PD-1/PD-L1 performed the worst. MAbs targeting SLAMF7 were not as effective as MAbs targeting CD38, however, they resulted in a lower incidence of adverse events in patients.

 

Given the different effects observed between the various MABs and treatment combinations, the authors suggested that their report “could provide a resource for clinicians when selecting an antibody to combine with other drugs for the treatment of MM.”