Clinical Outcomes Associated with Del(17p) in Newly Diagnosed Multiple Myeloma Treated with Triplet and Daratumumab-Based Quadruplet Induction Regimens

Background: del(17p) is an independent prognostic marker associated with poor clinical outcome identified in a number of studies and has been incorporated into risk stratification models for multiple myeloma (Palumbo A et al J Clin Oncol 2015). Recent studies have reported that the percentage of myeloma cells with del(17p) by fluorescent in situ hybridization (FISH) can have a significant impact on outcomes (Corre J et al. Blood 2021; Thakurta A et al. Blood 2019; Thanendrarajan S et al. Haematologica 2017). Different collaborative groups have recommended different cut-points for the presence of del(17p) with clinical significance ranging from ≥20% or >55% of affected cells. Herein, we examined clinical outcomes of newly diagnosed multiple myeloma (NDMM) patients with del(17p) treated with novel combination triplet and quadruplet induction regimens, including bortezomib, lenalidomide, dexamethasone (VRd), carfilzomib, lenalidomide, dexamethasone (KRd), +/- daratumumab (DVRd and DKRd). Methods: We conducted a chart review study of 578 NDMM patients treated with VRd, KRd, DVRd and DKRd at Memorial Sloan Kettering (MSK) from 1/1/2015 to 5/1/23. Cutoff date for analysis was 7/19/23. Only patients with available cytogenetic results (FISH and/or SNP-array) were included. Patients who received ≤1 prior cycle of another regimen for MM were included. We analyzed the percentage of cells with del(17p) by inter-phase FISH analyses and/or SNP-array with CD138 enrichment when FISH was not available. A cut-point of 20% for del(17p) was used (del(17p)