Prescriber Preference in Treatment of Relapsed or Refractory Multiple Myeloma (MM) and Diffuse Large B-Cell Lymphoma (DLBCL)

Background: Despite effective front-line therapies, DLBCL & MM have high relapse rates. Novel therapies like CAR-T & bispecific antibodies (BsAb) offer deep & durable remission compared to salvage therapies, but have a unique toxicity profile (TP) that requires monitoring. With no head-to-head trials, the rationale for therapy selection may vary. This study explores provider choices, sequencing preferences, & access barriers.

Methods: Two anonymous surveys (MM and DLBCL) of US-based Hematologists were conducted from 2/2024 to 6/2024, on practice settings, CAR-T & BsAb availability, treatment preferences & barriers. Responses were analyzed to assess preferences across clinical scenarios.

Results: Surveys were completed by 37 MM & 45 DLBCL providers. Most were at centers offering both CAR-T & BsAb. Most gave CAR-T inpatient, & BsAb outpatient. CAR-T was given by 73% MM providers & 66% DLBCL (92% used Cilta-cel, 96% used Ide-cel; 100% used Axi-cel, 90% used Liso-cel & 73% Tisa-cel). In MM, 78% used Teclistamab, 60% Talquetamab & 24% Elranatamab. In DLBCL, 62% used Epcoritamab & 40% Glofitamab.

Providers preferred CAR-T over BsAb in MM after 4+ prior lines of therapy (LOT) (89%), & in DLBCL after 2+ prior LOT (93%). CAR-T was favored more among academic providers & those at CAR-T centers. Practice volume did not impact selection. Among providers at centers with BsAb-only, CAR-T was preferred by 60% (MM) and 50% (DLBCL). Providers at centers without both favored CAR-T (MM: 75%, DLBCL: 86%).

CAR-T was chosen for better outcomes, short treatment, center choice, & prior experience. Other factors that influenced decisions were lower incidence of cytopenia/infection & “BsAb effective post-CAR-T, less so vice versa” (MM), & “curative potential of CAR-T” (DLBCL). Logistical barriers & institutional constraints influenced BsAb selection: CAR-T unavailability, access to specialized centers, referral complexity, insurance delay, manufacturing delay & hospitalization needs.

In MM, 78% providers preferred Cilta-cel over Ide-cel, especially academic providers & those with CAR-T experience. CAR-T volume did not impact selection. Cilta-cel was preferred due to perceived better response rate (RR), more experience, “progression-free survival (PFS) benefit”, center choice, & logistical issues with Ide-cel. Ide-cel was selected due to center choice, favorable TP & insurance preference. Teclistamab was preferred by 78% due to more experience, better RR, TP & center choice, Elranatamab by 11% (better TP, RR, & “PFS”), & Talquetamab by 11% due to having a non-BCMA target. Academic providers preferred Teclistamab (89% vs 50%), & nonacademic providers preferred Talquetamab (38% vs 4%) and Elranatamab (13% vs 8%).

In DLBCL after 2+ LOT, 69% favored Axi-cel due to prior experience, RR, center choice, & logistical issues with other products. Liso-cel & Tisa-cel were chosen by 27% & 2%, respectively, due to favorable TP. Axi-cel was also preferred 2^nd line by 73% for similar reasons, while 24% favored Liso-cel for its favorable TP. Epcoritamab was preferred by 56% (subcutaneous injection, more experience & center choice) & Glofitamab by 42% (shorter treatment duration, easy administration, more experience, & center choice). Practice setting & volume did not impact selection between products in DLBCL.

InBCMA-naïve MM pts, majority (97%) chose an anti-BCMA agent over GPRC5D due to better RR, TP, prior experience, & center choice. InBCMA-exposed pts, most (92%) favored an anti-GPRC5D agent. In contrast in DLBCL, 80% chose CD19 CAR-T after prior CD19-directed therapy, & 18% chose CD20 BsAb. Therefore, antigen escape was less of a concern in DLBCL vs MM. For relapse after 2^nd line CAR-T in DLBCL, 78% preferred BsAb over other salvage options due to better RR, TP, & more experience.

Providers prioritized RR, survival, & TP in decision making. Treatment logistics, duration, frequency, & cost were less crucial. MM providers also prioritized quality of life, which was less so in DLBCL. There were no differences in priority based on practice setting & experience with CAR-T.

Conclusion: The study highlights factors influencing therapy choices in MM & DLBCL. Despite CAR-T's potential for better outcomes, significant access barriers exist. Efforts to streamline referral pathways, logistics, & expanding availability are crucial to improve outcomes. Understanding these preferences & barriers can guide future management strategies.

Munoz:Pharmacyclics/Abbvie, Bayer, Gilead/Kite, Beigene, Pfizer, Janssen, Celgene/BMS, Kyowa, Alexion, Fosunkite, Seattle Genetics, Karyopharm, Aurobindo, Verastem, Genmab, Genzyme, Genentech/Roche, ADC Therapeutics, Epizyme, Beigene, Novartis, Morphosys/Incyte: Consultancy; Bayer, Gilead/Kite, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium, Novartis, BeiGene: Research Funding; Targeted Oncology, OncView, Curio, Genzyme, and Physicians' Education Resource: Honoraria. Bennani:Pfizer: Membership on an entity's Board of Directors or advisory committees; Acrotech Biopharma LLC: Membership on an entity's Board of Directors or advisory committees, Other: Advisory board. Paludo:Biofourmis: Research Funding; Karyopharm: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Research Funding. Cook:Geron Corp: Other: Held $600 Geron Stock for one week and sold without profit . Kourelis:Pfizer: Research Funding; Novartis: Research Funding. Villasboas Bisneto:Regeneron: Research Funding; Genentech: Research Funding; Epizyme: Research Funding; Enterome: Research Funding; CRISPR: Research Funding; Aptose: Research Funding. Wang:InnoCare, AbbVie: Consultancy; Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene, AstraZeneca, Genmab, AbbVie: Other: Advisory Board; Kite: Honoraria; Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab, AbbVie, BeiGene, Merck: Research Funding. Gertz:Johnson & Johnson: Other: personal fees; Janssen: Other: personal fees; Medscape: Honoraria; Alexion: Honoraria; Abbvie: Other: personal fees for Data Safety Monitoring board ; Astra Zeneca: Honoraria; Dava Oncology: Honoraria; Prothena: Other: personal fees; Alnylym: Honoraria; Sanofi: Other: personal fees; Ionis/Akcea: Honoraria. Iqbal:Sanofi US: Consultancy. Leung:Checkpoint Therapeutics: Current holder of stock options in a privately-held company; AbbVie: Current holder of stock options in a privately-held company. Kapoor:Amgen: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; X4 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding; Bristol Myers Squibb: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo Pharmaceuticals: Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Mustang Bio: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Ichnos: Research Funding; Angitia Bio: Membership on an entity's Board of Directors or advisory committees; CVS Caremark: Consultancy; Keosys: Consultancy. Kumar:Roche: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Other: Independent review committee participation; Sanofi: Research Funding; Novartis: Research Funding; Merck: Research Funding; MedImmune/AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dingli:Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; K36 Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Genentech: Consultancy; Sorrento: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Apellis: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria. Ansell:ADC Therapeutics: Research Funding; Pfizer: Research Funding; Bristol Myers Squibb: Research Funding; Affimed: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; SeaGen: Research Funding; AstraZeneca: Research Funding; Regeneron Pharmaceuticals, Inc.: Research Funding. Lin:NexImmune: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy; Caribou: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Legend: Consultancy.