Autologous Stem Cell Transplantation for Multiple Myeloma Patients Whose Myeloma Defining Event Was Slim

Background

In 2014, the IMWG updated the criteria for diagnosing multiple myeloma (MM) and added three additional criteria to the traditional CRAB criteria. The new criteria called the SLiM criteria, include clonal bone marrow plasma cells ≥60%, involved to uninvolved free light chain ratio (rFLC) ≥100 (involved FLC must be ≥ 100 mg/L), and > one focal lesion on MRI studies (each lesion ≥ 5 mm). These criteria were deemed myeloma-defining events (MDE) in the absence of CRAB criteria. Autologous stem cell transplantation (ASCT) has been used for treating MM for over three decades and is safe and efficacious.

We report on outcomes of outpatient ASCT in a cohort of patients with MM where therapy was initiated solely based on SLiM criteria.

Methods

We conducted a retrospective study of all patients diagnosed with MM based on SLiM criteria at Mayo Clinic, Rochester, MN. We compared this cohort to a matched cohort of newly diagnosed MM patients whose MDE was CRAB and who underwent an ASCT. For every patient whose MDE was SLiM, we matched two patients whose MDE was CRAB. The matching was done by age, gender, and melphalan dose.

Results

Between 2013 and 2022, 30 patients received an ASCT due to SLiM criteria at Mayo Clinic, Rochester (Durie Salmon Stage IA). The median age of our cohort was 63 (range 46-75) years, and 60% had an ISS of 1. Seventeen percent of the cohort was treated with DVRd induction. The median time from diagnosis to ASCT was 6.5 months (IQR 6-7), and all but one received full intensity conditioning with melphalan 200 mg/m². 53% of patients completed the ASCT without requiring hospitalization, and 47% (n=14) of patients required hospitalization with a median duration of hospital admission of 6 days (IQR 5-14). Bacteremia was confirmed in 7 patients (23%).

The matched cohort included 60 patients. Baseline characteristics were similar, with the exception of lower hemoglobin levels in the control group, as expected (13.1 vs 12, P=0.0017). No differences were seen in the number of cells collected (3.4 vs 3.67 X10⁶ cells/kg, P=0.19) or the use of Plerixafor (80% vs 78%, P=0.8). The SLiM cohort had a shorter median time to neutrophil (15 vs 16 days, P=0.049) and platelet (15 vs 17 days, P=0.0004) engraftment. Similar hospitalization and bacteremia rates were seen.

The overall response rate was 100%, with a complete response or better (sCR/CR) seen in 30% of patients. The matched cohort had an ORR of 98%, with sCR/CR of 37%. The MRD- rate was the same in both groups. More patients in the SLiM cohort achieved VGPR (50%) than in the CRAB cohort (27%). None of the patients died within 100 days of transplant. The 36-month OS was 100% in the SLiM group and 93.3% in the control group (95% CI 83.1%-97.4%), with a trend towards higher OS in the SLiM cohort (P=0.065). The 36-month PFS was 91.61% in the SLiM cohort (95% CI 69.93-97.87%) and 65.95% in the control group (95% CI 52.31%-76.53%). There was no difference in the PFS between the cohorts (P=0.414).

Conclusion

ASCT is efficacious and safe in MM patients transplanted only due to SLIM criteria. Improved MRD- and longer PFS were not seen despite lower ISS stage disease in the SLiM group.

Kumar:Novartis: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Other: Independent review committee participation; Merck: Research Funding; Sanofi: Research Funding; 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; 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; Celgene: 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. Dispenzieri:BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Pfizer: Research Funding; Janssen: Research Funding; HaemaloiX: Research Funding; Alnylam: Research Funding; Alexion: Consultancy, Research Funding. Dingli:BMS: Consultancy, Honoraria; Genentech: Consultancy; Janssen: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria; K36 Therapeutics: Research Funding; Apellis: Consultancy, Honoraria, Research Funding; Sorrento: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Alexion: Consultancy, Honoraria. Muchtar:Protego: Consultancy. Kapoor:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ichnos: Research Funding; GlaxoSmithKline: 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; Regeneron: Research Funding; Mustang Bio: Membership on an entity's Board of Directors or advisory committees; Angitia Bio: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Loxo Pharmaceuticals: Research Funding; Amgen: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; X4 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; CVS Caremark: Consultancy; Keosys: 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. Kourelis:Novartis: Research Funding; Pfizer: Research Funding. Gertz:Sanofi: Other: personal fees; Medscape: Honoraria; Prothena: Other: personal fees; Alnylym: Honoraria; Dava Oncology: Honoraria; Astra Zeneca: Honoraria; Janssen: Other: personal fees; Ionis/Akcea: Honoraria; Johnson & Johnson: Other: personal fees; Abbvie: Other: personal fees for Data Safety Monitoring board ; Alexion: Honoraria.