Introduction: Ven is a BCL2 inhibitor that has shown clinical efficacy in RRMM patients (pts) particularly those that harbor t(11;14). Ven has been evaluated in clinical trials as a single agent, in combination with dexamethasone (dex), immunomodulatory drugs (IMiD), proteasome inhibitors (PI), and anti-CD38 monoclonal antibodies (MAb) yet its place in the therapeutic landscape remains in question. In this retrospective analysis, we aim to evaluate the real-world efficacy of Ven-based regimens in RRMM pts treated outside of a clinical trial across the 3-site MCCC.

Methods: We retrospectively analyzed the medical records of pts with RRMM treated with Ven-based regimens between January 2015 and October 2023 at the MCCC. Refractoriness was defined by progression on or within 60 days of stopping treatment. Categorical variables were compared with Chi-square tests and continuous variables were compared with t-tests. Outcomes were estimated using the Kaplan-Meier method and curves were compared between the groups using log-rank tests.

Results: 83 pts were included in the analysis. The median age was 71 (39-93), 63% were male, 93% were white, 27% had ISS III, 18% had high risk cytogenetics (HRCyto), 76% had t(11;14), the median prior lines of therapy (LOT) was 4 (1-15), 68% received ≥ 4 prior LOT, 87% received prior autologous transplant, 58% were triple-class refractory (TCR), 64%/23% were penta-drug exposed/refractory (PDE/R), 8% received prior BCMA-directed therapies (BDT), 58% received Ven+dex, 25% received Ven+PI +/-dex, 6 % received Ven+anti-CD38 MAb+/-dex and 11% received Ven+other. The median follow-up time from start of a Ven-based regimen was 29 months (mo). The median Ven dose was 800mg (20-1600) with 25% of pts receiving Ven ramp-up dosing. The overall response rate (ORR) to a Ven-based regimen was 58% and was 64% for pts with t(11;14) and 40% for pts without t(11;14); p=0.06. Ven-treated pts with HRCyto had inferior PFS (3mo) and OS (8mo) compared to patients who did not have HRCyto who had a PFS of 9mo (p=0.020) and OS of 80mo (p<0.001). The ORR for TCR and PDR pts were 52% and 42%, respectively. No significant ORR differences were noted across the different Ven-based regimens (p=0.32). The median PFS for pts with t(11;14) was 10mo compared to 2mo for pts w/o t(11;14); p=<0.001. The median OS for pts with t(11;14) was 80mo compared to 10mo for pts without t(11;14); p=0.001. Ven-treated pts who received 1-3 prior LOT has superior ORR, median PFS, and median OS; 89%, 25mo, and 99mo, respectively, compared to pts who received ≥4 prior LOT who achieved an ORR of 43% (p<0.001), median PFS of 5mo (p<0.001) and median OS of 25mo (p<0.001). Ven-treated pts that were TCR had inferior PFS (5mo) and OS (26mo) compared to pts who were not TCR who achieved a PFS of 12mo (p<0.001) and a median OS of 80mo (p=0.02).Ven-treated pts that were PDR had inferior PFS (4mo) and OS (22mo) compared to pts who were not PDR who achieved a PFS of 9mo (p<0.001) and a median OS of 80mo (p=0.02).Ven-treated pts who received prior BDT (n=7) achieved an ORR of 29% and had a median PFS and OS of 2mo and 6mo, respectively on a Ven-based therapy. 59 pts received additional therapy in the post Ven-progression setting. The ORR to post-Ven progression therapies was 53% (n=31/59), the median PFS was 9mo and median OS was 35mo. The most common post-Ven progression regimens used were PI-based (n=16; ORR=56%), anti-CD38 MAb-based (n=14; ORR=50%), BDT (n=12; ORR=83%), selinexor-based (n=3; ORR=0%) with BDT resulting in highest ORR (p=0.048) and PFS (p=0.005).

Conclusions: Ven-based regimens are effective in heavily pre-treated pts with RRMM however they are more effective when used within 1-3 prior LOT, in pts with t(11;14), and in pts without HRCyto, TCR or PDR MM. BDT appear to be the most efficacious therapies in the post-Ven progression setting.

Disclosures

Parrondo:Bristol Myers Squibb, GSK: Research Funding; AstraZeneca: Honoraria; Sanofi Aventis: Honoraria. Fonseca:Patent for FISH in MM - ~$2000/year: Patents & Royalties: Patent for FISH in MM - ~$2000/year; AbbVie, Adaptive, Amgen, Apple, Bayer, BMS/Celgene, Gilead, GSK, Janssen, Kite, Karyopharm, Merck Sharp & Dohme, Juno Therapeutics, Takeda, Arduro Biotech, Oncotracker, Oncopeptides, Pharmacyclics, Pfizer, RA Capital, Regeneron, Sanofi: Consultancy; Celgene, Bristol Myers Squibb, Bayer, Amgen, Janssen, Kite, a Gilead company, Merck Sharp & Dohme, Juno Therapeutics, Takeda, AbbVie, Aduro Biotech, Sanofi, OncoTracker: Honoraria; Antengene: Membership on an entity's Board of Directors or advisory committees. Kapoor:Karyopharm: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Ichnos: Research Funding; Loxo Pharmaceuticals: Research Funding; Angitia Bio: Membership on an entity's Board of Directors or advisory committees; Mustang Bio: Membership on an entity's Board of Directors or advisory committees; BeiGene: 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; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Research Funding; Regeneron: Research Funding; GlaxoSmithKline: 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; Amgen: 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; CVS Caremark: Consultancy; Keosys: Consultancy. Gertz:Alnylym: Honoraria; Sanofi: Other: personal fees; Prothena: Other: personal fees; Alexion: Honoraria; Dava Oncology: Honoraria; Astra Zeneca: Honoraria; Medscape: Honoraria; Janssen: Other: personal fees; Abbvie: Other: personal fees for Data Safety Monitoring board ; Johnson & Johnson: Other: personal fees; Ionis/Akcea: Honoraria. Dispenzieri:Alnylam: Research Funding; Takeda: Consultancy, Research Funding; HaemaloiX: Research Funding; BMS: Consultancy, Research Funding; Janssen: Research Funding; Pfizer: Research Funding; Alexion: Consultancy, Research Funding. Sher:Caelum pharma: Other; Alpha: Consultancy, Membership on an entity's Board of Directors or advisory committees; 2 Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Prothena: Other. Cook:Geron Corp: Other: Held $600 Geron Stock for one week and sold without profit . Dingli:Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Sorrento: Consultancy, Honoraria; K36 Therapeutics: Research Funding; Regeneron: Consultancy, Honoraria; Apellis: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Genentech: Consultancy; MSD: Consultancy, Honoraria; Alexion: Consultancy, Honoraria. Lin:NexImmune: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Sanofi: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy; Caribou: Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy; Legend: Consultancy; Janssen: Consultancy, Research Funding. Muchtar:Protego: Consultancy. Kourelis:Pfizer: Research Funding; Novartis: Research Funding. Leung:Checkpoint Therapeutics: Current holder of stock options in a privately-held company; AbbVie: Current holder of stock options in a privately-held company. Baughn:Genentech: Consultancy. Kumar:Janssen: 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; Roche: Research Funding; KITE: 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; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; MedImmune/AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Sanofi: Research Funding; Oncopeptides: Other: Independent review committee participation. Chanan-Khan:Starton Therapeutics: Membership on an entity's Board of Directors or advisory committees. Ailawadhi:Sanofi: Consultancy; GSK: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Abbvie: Research Funding; Xencor: Research Funding; Ascentage: Research Funding; Cellectar: Consultancy, Honoraria, Research Funding; Johnson and Johnson: Consultancy, Research Funding; Regeneron: Consultancy; Beigene: Consultancy; Takeda: Consultancy; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacuclics: Consultancy, Research Funding.

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2024
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