US Physicians' Perspective and Practice Patterns for the Management of Transplant-Eligible-Newly Diagnosed Multiple Myeloma
Authors: Shatnawi Yara , Motiwala Zainab , Anwer Faiz , Dima Danai , Williams Louis S , Ahmed Nausheen , Mazzoni Sandra , Khouri Jack , Rudoni Joslyn , Rice Mikhaila , Basali Diana , Samaras Christy J. , Valent Jason , Abdallah Al-Ola , Roy Tara , Faiman Beth M. , Raza Shahzad 
Published: December 2024

Introduction: Triplet therapy with a proteasome inhibitor (PI), immunomodulator (IMiD) and dexamethasone (D) is the standard induction regimen for TE-NDMM. However, as new phase III trials supporting quadruplet therapy incorporating anti-CD38 antibody emerge, there is no clear consensus on induction, consolidation and maintenance therapy (MT). This survey aims to understand the perspective of US hematologists/oncologists (HO) perspective in treating TE-NDMM.

Methods: A cohort of experienced US hematologist/oncologists (HO) from both academic institutions and community centers participated in survey aimed at approach to induction, consolidation and maintenance treatments in TE-NDMM. The survey was conducted from May 2024 to July 2024. Respondents were stratified based on their FISH results “high risk”, “standard risk” as well as “no” FISH results, followed by induction, consolidation, MT and Minimal residual disease (MRD) assessment. Choice of induction regimen included VRD, DaraVRD, KRD, DaraKRD, VCD, Dara-VCD, or others.

Results: Responses were collected from 37 U.S HO. 22 (59%) affiliated with NCCN/NCI. 17 (46%) sub-specialized in MM, 14(38%) identified as stem cell transplanters, and 20 (54%) were general HO. Respondents averaged 12 years of experience (range: 2-41 years) in treating TE-NDMM.

Among high-risk FISH patients, 25 (78%) selected DaraVRD induction, 5 (16%) chose DaraKRD, and 2 (6%) opted for VRD. Of those who selected DaraVRD, 22 (88%) used weekly subcutaneous (SC) bortezomib (V), 18 (72%) administered Lenalidomide (R-25mg) on a d1-d21/28-day cycle, and 13 (52%) used weekly dexamethasone (D) at 40mg. 9 (36%) respondents continued daratumumab (Dara) during post-transplant consolidation. For MT, 10 (40%) selected VR, 5 (20%) chose only R, and 3 (12%) preferred DaraVR. 3(12%) based their MT decisions on bone marrow biopsy (BMBx) and MRD assessment.

Among those selected DaraKRD, 4 (80%) used once-weekly Carfilzomib (K) on days 1,8,15 of a 28-day cycle, 5(80%) used R-25mg on a d1-d21/28-cycle, and D was split between 20mg (50%) and 40mg (50%) dosages. For consolidation, 3 (75%) used DaraKRD and 1 (25%) used KRD. For post-transplant MT, 2 (40%) respondents chose KR and 3(60%) selected DaraKR.

Among standard-risk FISH patients, 20 (63%) of HO selected DaraVRD induction and 12 (38%) chose VRD. For DaraVRD respondents, 17 (85%) used weekly SC V, 13 (65%) administered R-25mg on a d1-d21/28-day cycle, and 11 (55%) used weekly D-40mg. Only 6 (30%) continued Dara during consolidation. For MT, 16 (80%) respondents used only R, and 3 (15%) based their decisions on BMBx and MRD assessment.

When FISH results were unavailable, 27 (73%) selected DaraVRD induction and 10 (27%) chose VRD. Among DaraVRD respondents, 26 (96%) used weekly SC V, 18 (67%) administered R-25mg on a d1-d21/28- cycle, and 17 (63%) used weekly D-40mg. 12 (44%) integrated Dara during consolidation. For MT, 18 (67%) respondents prescribed only R therapy, 2 (7%) chose VR, 2 (7%) chose DVR, and 5 (19%) would repeat BMBx and MRD assessment. Among those who selected VRD alone, 9 (90%) used weekly SC V, R-25mg on d1-d14 and d1-d21 were (50%) each, and 6 (60%) used weekly D-40mg.

When FISH results were unavailable, 27 (73%) of HO selected DaraVRD induction and 10 (27%) chose VRD. Among DaraVRD respondents, 26 (96%) used weekly SC V, 18 (67%) administered R 25 mg on a d1-d21/28-cycle, and 17 (63%) used weekly D 40 mg. 12 (44%) continued Dara during consolidation. For MT,18 (67%) respondents prescribed only R therapy, 2 (7%) chose VR, 2 (7%) chose DVR, and 5 (19%) would repeat BMBx and MRD assessment. Among those who selected VRD alone, 9 (90%) used weekly SC V, R-25 mg on d1- d14 (50%) and d1-d21 (50%) and 6 (60%) used weekly D-40 mg.

Overall, 79% did not base their maintenance therapy decisions on MRD results.

Conclusion: This study highlights substantial differences among US physicians in the induction, post-transplant consolidation, and maintenance management of TE-NDMM. The survey results indicate variability in choice of induction, treatment schedules, modes of administration and dosing compared to large phase III trials. These decisions likely reflect the prior experiences of physicians based on efficacy, toxicity and tolerability. The results from our survey will provide valuable insights that can incorporate the US perspective into future MM clinical trials.