Clinical consensus on first-line (1L) treatments for transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM): delphi panel of US hematologists and oncologists

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Treatment for NDMM has evolved substantially in the last decade. However, despite established guidelines, there is a lack of uniformity in prescribing patterns. Monotherapy and doublets with suboptimal efficacy are still prescribed as 1L therapy, with triplets reserved for later lines, leading to a missed opportunity to achieve the best long-term outcomes. Moreover, guidelines do not provide definitive recommendations on anti–CD38- vs proteasome inhibitor-based triplets in 1L, and there are no head-to-head trial data for these regimens that would aid decision making. Aims: This study aimed to obtain clinical consensus from a panel of multiple myeloma (MM) experts on factors impacting 1L prescribing, challenges with existing therapies, optimal duration of therapy (DoT), and treatment decision making for TIE NDMM. Methods: A modified Delphi Panel with 2 online survey rounds and a virtual consensus meeting was used. US-based hematologists/oncologists who treat TIE patients with NDMM were selected as expert panelists. Consensus was defined as ≥80% of panelists rating their agreement/disagreement within a 3-point range at either end of a 9-point Likert scale. The panel was double blinded to maintain study integrity and to prevent bias. Results: Eighteen experts with an average of 18.8 years in practice (119.7 MM appointments/month; 104.7 patients with MM/month) completed both surveys; 9 of them participated in the consensus meeting. Consensus was reached that frailty (89%), poor ECOG PS score (83%), and comorbidities (89%) have a strong impact on treatment selection, in addition to the treatment’s effect on progression-free survival (PFS), overall survival (OS), and its adverse event profile. Panelists agreed that it is important to use the most efficacious regimen (one which best improved PFS and OS) as 1L therapy either always or in most cases (100%). Sixteen (89%) panelists considered one regimen to be more efficacious than other regimens; of these, 88% considered daratumumab (D), lenalidomide (R), dexamethasone(d) (DRd) or D-containing quadruplet (quad) regimens as most efficacious for use as 1L therapy for TIE NDMM. Neuropathy was cited as the greatest challenge in treating TIE NDMM with bortezomib (V; 94%), with 89% of panelists stating that it has prevented them from prescribing V. Regarding optimal DoT, panelists agreed that the treatment should be continued until progression as long as benefits outweigh risk (89%). Summary/Conclusion: A panel of MM experts reached clinical consensus that it is important to use the most efficacious regimen as 1L therapy for TIE NDMM. DRd or D-containing quad regimens were considered by most as the most efficacious 1L therapy for TIE NDMM. These data may aid physician decision making in the absence of head-to-head trials among current triplet and quad regimens. Keywords: Myeloma, Multiple myeloma