Consensus Guidelines and Recommendations for The CD38 Monoclonal Antibody-based Quadruplet Therapy and Management in Clinical Practice for Newly Diagnosed Multiple Myeloma: From the Pan-Pacific Multiple Myeloma Working Group.

Abstract

The therapeutic outcomes of clinical trials for incorporating anti-CD38 monoclonal antibodies (including isatuximab and daratumumab) into the bortezomib/lenalidomide/dexamethasone (VRd) triplet therapy backbone as the first-line treatment for newly diagnosed multiple myeloma (NDMM) have demonstrated significant improved efficacies. From a safety perspective, the addition of anti-CD38 monoclonal antibodies into the triplet therapies did not raise additional safety concerns. Based on the promising results, the National Comprehensive Cancer Network (NCCN) Guidelines Version 1.2025 had updated the quadruplet therapy incorporating anti-CD38 monoclonal antibodies with VRd-based therapies as the primary therapy for both transplantation-eligible and transplantation-ineligible NDMM patients. Thus, a panel of experts in hematology and oncology with extensive experience in the treatment of NDMM was convened in 2024 to develop consensus recommendations based on recent evidence from pivotal clinical trials and real-world practices, providing clear guidance for optimizing treatment strategies in both transplantation-eligible and transplantation-ineligible patients. The main topics identified for discussion and recommendation were: (i) the benefits and indications for quadruplet therapy for NDMM; (ii) the optimization of quadruplet therapy strategies; (iii) the management and monitoring of potential adverse events for quadruplet therapy, and (iv) the impact of quadruplet regimens on tandem stem cell transplantation and maintenance treatment. Recommendations were then presented to the entire panel for further discussion and amendment before voting. This manuscript presents the recommendations developed, including findings from the expert panel discussions, consensus recommendations and a summary of evidence supporting each recommendation.