Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Plasma Cell Disorders, Clinical Research, Diseases, Lymphoid Malignancies, Human, Study Population, Measurable Residual Disease
Patients and Methods: We conducted a retrospective, single-center study of patients achieving at least VGPR after ASCT between 01/01/2016 and 12/30/2023, majority (n=814, 98%) received ASCT in the frontline setting. MRD testing was performed between days 60-100 post-transplant using next-generation flow cytometry with a sensitivity of at least 1x10^5 nucleated cells (minimum 2x10^6 cells assessed). Treatment response and disease progression were determined by IMWG criteria. High-risk disease (HRD) was defined as presence of International Staging System ISS stage 3, high lactate dehydrogenase, 1q gain, 17p deletion, or t(4;14) chromosomal abnormalities. We calculated PFS/OS from transplant day 0 to first documented event (progression or death). Categorical variables were compared using chi-square and Fisher’s exact tests. Non-parametric tests compared continuous variables, and logistic regression analyses tested associations between clinical/lab variables and MRD status post-ASCT. Time-to-event analyses were performed using Kaplan-Meier and compared using log-rank test. Multivariable analyses were conducted using the Cox regression model.
Result: The study cohort included 831 newly diagnosed MM patients. The median follow-up for the cohort was 50 months (95% CI: 48-51). 48% (n=402) achieved MRD negativity (MRD-neg) post-ASCT. Univariate analysis demonstrated that R2-ISS stage, depth of response pre-ASCT, and presence of t(11;14) to be associated with worse MRD-negativity rates. Multivariate analysis revealed that t(11;14) significantly decreased the odds of MRD-negativity (p<0.0001, OR=0.4, 95% CI: 0.3-0.6) and a deeper pre-ASCT response was associated with increase odd of MRD-negativity OR-4.7 (95%CI 3.2-7.4) p<0.0001.
Patients with MRD-positive disease post-transplant had an inferior estimated median PFS of 57.6 months (95% CI: 49-69) with a 5-year PFS of 49% (95% CI: 43-56), compared to an estimated median PFS of 83.3 months (95% CI: NA) and a 5-year PFS of 66% in MRD-negative patients (p<0.0001, HR=1.9, 95% CI: 1.5-2.5). Similarly, MRD positivity was associated with an inferior OS [estimated median of 92.6 months (95% CI NA) ,5-year OS 76% (95%CI 72-82) for MRD-pos vs. Median OS NR, 5-year OS 85%(95%CI NA) in MRD-neg; p=0.003, HR=1.69, 95% CI: 1.2-2.38)]. In MRD-neg patients, a baseline bone marrow plasma cells BMPC% >60% was significantly associated with worse PFS (HR=1.9, 95% CI: 1.26-2.99; p<0.01).
High-risk disease was not associated with an inferior PFS or OS in patients with MRD-negativity. For MRD-neg patients, estimated median PFS was not reached for those without HRD, 5-year PFS was 66% (95%CI 51-85), compared to 83 months(95%CI 65-NA) for those with HRD, 5-year PFS was 65%(95%CI57-74), p=0.6441. The median OS was not reached in either group (p=0.07). Five-year OS was 94% (95%CI 86-100) in MRD-neg without HRD vs. 81%(95%CI 75-87) with HRD (p=0.07). In MRD-pos patients, median PFS was 81 months (95%CI 58-NA) for those without HRD, 5-year PFS of 59% (95%CI 46-77), compared to PFS of 41 months(95%CI 36-52) for those with HRD ,5-year PFS of 39% (95%CI 31.3-47) , p=0.003. Median OS was not reached in MRD-pos patients without HRD, but it was 59.8 months ( for those with HRD (p=0.0012). Five-year OS was 94% (95%CI 89-99) in MRD-pos without HRD vs. 67%(95%CI 60-74) with HRD (p<0.0001).
For every 1 log increase in the residual cell % on MRD testing in MRD-pos patients, the hazard ratio for PFS increased by 42% (p=0.0002, HR=1.42, 95% CI: 1.2-1.7).
Conclusion: Patients with t(11;14) have a reduced likelihood of achieving MRD negativity post-ASCT, whereas high-risk cytogenetics did not impact MRD-negativity rates. Achievement of MRD negativity post-ASCT mitigates the impact of high-risk characteristics.
Disclosures: Gertz: Alexion: Honoraria; Johnson & Johnson: Other: personal fees; Astra Zeneca: Honoraria; Abbvie: Other: personal fees for Data Safety Monitoring board ; Medscape: Honoraria; Dava Oncology: Honoraria; Prothena: Other: personal fees; Sanofi: Other: personal fees; Janssen: Other: personal fees; Alnylym: Honoraria; Ionis/Akcea: Honoraria. Dispenzieri: HaemaloiX: Research Funding; Alnylam: Research Funding; Alexion: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Research Funding; Janssen: Research Funding. Muchtar: Protego: Consultancy. Kapoor: Karyopharm: Research Funding; GlaxoSmithKline: 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; Ichnos: Research Funding; 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; 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; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; X4 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Angitia Bio: Membership on an entity's Board of Directors or advisory committees; CVS Caremark: Consultancy; Keosys: Consultancy; Loxo Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; Regeneron: Research Funding; Amgen: Research Funding. Kourelis: Novartis: Research Funding; Pfizer: Research Funding. Dingli: Regeneron: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; K36 Therapeutics: Research Funding; MSD: Consultancy, Honoraria; Sorrento: Consultancy, Honoraria; Apellis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Genentech: Consultancy. Leung: AbbVie: Current holder of stock options in a privately-held company; Checkpoint Therapeutics: Current holder of stock options in a privately-held company. Cook: Geron Corp: Other: Held $600 Geron Stock for one week and sold without profit . Lin: Genentech: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; NexImmune: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; Janssen: Consultancy, Research Funding; Legend: Consultancy; Celgene: Consultancy, Research Funding. Hwa: Pfizer: Other: Consulting fee located to Mayo Research fund; MultiMedia Medical, LLC: Consultancy; Shield Therapeutics: Honoraria; Janssen: Honoraria; GSK: Honoraria. Kumar: Abbvie: 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; Janssen: 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; Adaptive: 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; MedImmune/AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Novartis: Research Funding; Roche: Research Funding; Sanofi: Research Funding; Oncopeptides: Other: Independent review committee participation.
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