Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, Adult, Translational Research, Clinical Research, Plasma Cell Disorders, Diseases, Lymphoid Malignancies, Study Population, Human
Methods: Patients with active MM diagnosed between January 2013 and January 2023 with a flow cytometry-based S-phase assessment at diagnosis were included. Flow cytometric immunophenotyping was performed using the following antibodies: CD19, CD38, CD45, CD138, cytoplasmic kappa and lambda immunoglobulin, and DAPI (4',6-diamidino-2-phenylindole). The percentage of plasma cells in S-phase was determined by measuring the proportion of cells with DNA content of the monotypic plasma cells between the G0/G1 and G2/M peaks. Plasma cell clonality was detected through demonstrating CD38 and CD138 positivity along with immunoglobulin light chain restriction, abnormality of CD19/ CD45 expression and/or ploidy difference by DAPI staining. High-risk cytogenetic abnormalities (HRCA) by FISH were defined as follows: presence of deletion 17p (del17p), t(4;14), t(14;16), t(14;20), 1q gain/amplification, 1p deletion (when available). Additionally, the second iteration of the revised ISS (R2-ISS), incorporating both laboratory and cytogenetic features as well an adaptation of the recently proposed International Myeloma Working Group (IMWG) Classification for high-risk disease, was utilized for risk stratification. All time-to-event analyses were performed using the Kaplan Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards analyses were performed to assess the independent prognostic impact of S-phase.
Results: A total of 823 patients were included in the study. The median follow-up was 6 years [95% Confidence interval (CI): 5.5-6.3 years] and estimated median overall survival (OS) was 8.3 years. The median S-phase value for the cohort was 0.8 % (interquartile range: 0.5-1.4%), with 135 (16%) patients harboring an S-phase of ≥2% at diagnosis. Applying the R2-ISS prognostic model to our cohort, 11% (79/706) patients were stratified to the R2-ISS high-risk cohort; 93 patients (out of 788, 12%) had 2 or more HRCA at diagnosis. Patients with a S-phase ≥2% at diagnosis had a median OS of 3.9 years (95% CI: 2.9-5.7) vs. 9.2 years [95% CI: 7.9-not reached (NR)] for patients with a S-phase <2% [Hazard ratio (HR): 2.2 (95% CI: 1.7-2.8), p<0.0001]. The median OS was inferior for cohorts with an increasing S-phase value: S-phase of 0.1-1%: HR: 1 (standard), S-phase 1.1-3%: HR 1.7 (95% CI: 1.3-2.1), S-phase >3%: HR 3.0 (95% CI: 2.2-4.1)].
On a multivariable analysis including S-phase ≥2%, age at diagnosis of MM (>65 years) and R2-ISS high-risk status, S-phase ≥2% was an independent predictor of inferior OS [hazard ratio (HR) 1.9 (95% CI: 1.4-2.6), p<0.0001]. Age >65 years [HR 1.9 (95% CI: 1.5-2.5), p<0.0001] and R2-ISS high-risk status [HR 1.8 (1.3-2.6), p=0.001] were also independent predictors of OS. Within the sub cohort of patients with 2 or more of the listed high-risk cytogenetic features (n=93, 12%), a S-phase ≥2% (n=24) was associated with a worse median OS of 1.6 years (95% CI: 0.7-NR) vs. 6.2 years (95 % CI:3.3-NR) for S-phase <2% (p=0.002).
Conclusion: Flow cytometry-based determination of the proportion of monotypic plasma cells in S-phase is an easy-to-study and powerful prognostic tool for NDMM. A S-phase of ≥2% at diagnosis is a predictor of OS independent of age and R2-ISS high-risk stage. An S-phase of ≥2% was able to identify a distinct group with markedly inferior outcomes even within the sub cohort of patients with 2 or more high-risk cytogenetic features.
Disclosures: Kapoor: Loxo Pharmaceuticals: Research Funding; Kite: 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; Karyopharm: Research Funding; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; AbbVie: 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; Mustang Bio: Membership on an entity's Board of Directors or advisory committees; Sanofi: 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; Ichnos: Research Funding; Angitia Bio: Membership on an entity's Board of Directors or advisory committees; X4 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Keosys: Consultancy; Bristol Myers Squibb: Research Funding; Regeneron: Research Funding; Amgen: Research Funding. Cook: Geron Corp: Other: Held $600 Geron Stock for one week and sold without profit . Dispenzieri: Janssen: Research Funding; Alexion: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; HaemaloiX: Research Funding; Alnylam: Research Funding; BMS: Consultancy, Research Funding; Pfizer: Research Funding. Dingli: Genentech: Consultancy; Sorrento: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; K36 Therapeutics: Research Funding; BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Apellis: Consultancy, Honoraria, Research Funding; Alexion: Consultancy, Honoraria. Kourelis: Novartis: Research Funding; Pfizer: 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. Lin: Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Research Funding; Caribou: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Research Funding; Sanofi: Consultancy; NexImmune: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Legend: Consultancy; Celgene: Consultancy, Research Funding; Regeneron: Consultancy. Muchtar: Protego: Consultancy. Hwa: GSK: Honoraria; MultiMedia Medical, LLC: Consultancy; Shield Therapeutics: Honoraria; Janssen: Honoraria; Pfizer: Other: Consulting fee located to Mayo Research fund. Kumar: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Merck: Research Funding; Takeda: 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; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Other: Independent review committee participation; Abbvie: 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; Novartis: Research Funding; Sanofi: Research Funding.
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