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1981 Real World Outcomes with Venetoclax (Ven)-Based Therapies in Patients with Heavily Pretreated Relapsed/Refractory Multiple Myeloma (RRMM): A Mayo Clinic Comprehensive Cancer Center (MCCC) Experience

Program: Oral and Poster Abstracts
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Poster I
Hematology Disease Topics & Pathways:
Combination therapy, Plasma Cell Disorders, Diseases, Therapy sequence, Treatment Considerations, Lymphoid Malignancies, Human
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Ricardo D. Parrondo, MD1, Saurav Das, MD2*, Hanna Sledge3*, Abiola Bolarinwa, MBBS, FMCPath4*, Jamie Elliott, ANP5*, Andre Fernandez, P.A. -C1*, David O. Hodge3*, Leif Bergsagel, MD6, Rafael Fonseca, MD7, Prashant Kapoor, MD8, Francis Buadi, MD4, Morie A. Gertz, MD4, Angela Dispenzieri, MD4, Vivek Roy, MD1, Taimur Sher, MD9*, Moritz Binder, MD4, Nadine Abdallah, MD8, Saurabh Chhabra, MBBS10*, S. Vincent Rajkumar, MD4*, Wilson I. Gonsalves, MD11, Joselle Cook, MBBS4, David Dingli, MD, PhD4, Saurabh Zanwar, MD4*, Yi Lin, MD, PhD4, Eli Muchtar, MD4, Caitlin Wilson5*, Udit Yadav, MBBS10*, Rahma M Warsame, MD4, J E Wiedmeier-Nutor, MD, MPH10, Taxiarchis Kourelis, MD4, Nelson Leung, MD12, Madhu Nagaraj, MD4*, Mustaqeem A. Siddiqui, MD, MBA4, Linda B. Baughn, PhD13, Shaji Kumar, MD4, Asher A. Chanan-Khan, MD1 and Sikander Ailawadhi1

1Division of Hematology-Oncology, Mayo Clinic-Florida, Jacksonville, FL
2Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL
3Department of Quantitative Health Sciences, Mayo Clinic Florida, Jacksonville, FL
4Division of Hematology, Mayo Clinic, Rochester, MN
5Mayo Clinic Florida, Jacksonville
6Division of Hematology/Oncology, Mayo Clinic, Phoenix, AZ
7Division of Hematology, Mayo Clinic, Paradise Valley, AZ
8Mayo Clinic, Rochester, MN
9Division of Hematology, Mayo Clinic, Jacksonville, FL
10Division of Hematology/Oncology, Mayo Clinic Arizona, Phoenix, AZ
11Division of Hematology, Mayo School of Graduate Medical Education, Rochester, MN
12Division of Nephrology, Hematology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
13Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN

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: GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; X4 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Loxo Pharmaceuticals: Research Funding; Pharmacyclics: 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; Janssen: Membership on an entity's Board of Directors or advisory committees; Angitia Bio: Membership on an entity's Board of Directors or advisory committees; Keosys: Consultancy; CVS Caremark: Consultancy; Mustang Bio: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Research Funding; Sanofi: 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; Ichnos: Research Funding; Regeneron: Research Funding; Amgen: Research Funding. 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: Pfizer: Research Funding; Alnylam: Research Funding; Alexion: Consultancy, Research Funding; Janssen: Research Funding; HaemaloiX: Research Funding; Takeda: Consultancy, Research Funding; BMS: 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.

*signifies non-member of ASH