Outcomes of Patients with Multiple Myeloma with Deletion 1p Following Autologous Stem Cell Transplant

Background: Deletion of the short arm of chromosome 1 (del1p) has been speculated to be associated with worse outcomes in patients diagnosed with multiple myeloma (MM). There are scarce data on the outcomes of MM patients with del1p following autologous hematopoietic stem cell transplantation (autoHCT).

Methods: We conducted a single-center, retrospective analysis of patients with MM and del1p who underwent upfront autoHCT between 1988 and 2021. We also conducted 2:1 propensity score matching (PSM) between patients with standard-risk MM without del1p and the del1p MM cohort, according to the following variables: age at autoHCT, year of autoHCT, R-ISS stage, HCT-CI (≤ 3 vs. > 3), type of induction treatment, type of conditioning and use of post-transplant maintenance. High-risk cytogenetics were defined as del17p, t(4;14), t(14;16), 1q21 gain or amplification (1q+) by fluorescence in situ hybridization. Clinical response, relapse, and progression were defined by the International Myeloma Working Group criteria. Primary outcomes were progression-free survival (PFS) and overall survival (OS).

Results: Fifty-five patients with del1p MM were included in the study. Twenty-eight (51%) patients were male and the median age at transplant was 64 years (range 43-78). Most patients had either R2-ISS stage III (n=28, 51%) or II (n=14, 25%) disease. Thirty-five (64%) patients had concomitant 1q+ and 13 (24%) had concomitant deletion 17p.

At day 100 post-transplant, 91% (n=50) of patients achieved ≥ very good partial response (VGPR), including 25 (45%) with complete response (CR). At best post-transplant response, 100% of patients achieved ≥VGPR, including 35 (64%) with CR.

After a median follow-up of 24.0 months (range 3.8-79.5), the median PFS for the cohort was 30.2 months (95% CI 18.0 - not reached (NR)) and the median OS was not reached (95% CI 41.1 - NR). In multivariable analysis, female patients (HR 2.81, 95% CI 1.14-6.91; p=0.025) and those with R2-ISS stage IV (HR 4.85, 95% CI 1.01-23.34; p=0.049) had worse PFS, whereas patients who achieved CR at best post-transplant response had better PFS (HR 0.38, 95% CI 0.16-0.91; p=0.029). Patients with concomitant deletion 17p had worse OS (HR=4.47, 95% CI 1.18-17.02; p=0.028) in multivariable analysis.

After PSM, the 55 patients in the del1p were compared to 110 patients with SRMM without del1p. Baseline characteristics were mostly balanced between the two groups, though patients in the del1p group more often received a busulfan+melphalan based conditioning regimen compared to the non-del1p SRMM group (35% vs 17%, p=0.018). There was no significant difference between the two groups in PFS (HR 1.63, 95% CI 0.86-3.10; p=0.13) or in OS (HR 1.77, 95% CI 0.73-4.32; p=0.21), adjusting for conditioning regimen.

Conclusions: We report one of the largest studies to date on outcomes of MM patients with del1p following autoHCT. Median PFS was just over 30 months and median OS was not reached. Patients with concomitant deletion 17p had inferior OS. In a PSM analysis, patients with del1p MM who received autoHCT had comparable survival outcomes to those of SRMM patients without del1p, suggesting that del1p might not have a major detrimental prognostic impact in MM patients who undergo autoHCT.

Bashir:Stemline Therapeutics, Inc.: Research Funding; GSK PLC: Research Funding; Pfizer, Inc.: Research Funding. Srour:Hansa Biopharma: Consultancy; Orca Bio: Research Funding. Kebriaei:Pfizer: Consultancy, Honoraria; Jazz Pharmaceuticals: Consultancy, Honoraria. Lee:Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Allogene: Consultancy; Pfizer: Consultancy; Abbvie: Consultancy; Regeneron: Consultancy, Research Funding; Amgen: Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Sanofi: Consultancy. Patel:Merck: Consultancy; Pfizer: Consultancy; Johnson & Johnson (Janssen): Consultancy; Caribou Sciences: Consultancy; Sanofi: Consultancy; Poseida: Consultancy; Kite, A Gilead company: Consultancy, Other: scientific advisory board; Genentech: Consultancy; Abbvie: Consultancy; Takeda: Consultancy; BMS: Consultancy, Other: chair of scientific advisory board ; AstraZeneca: Consultancy; Oricel: Consultancy, Other: Chair of scientific board. Thomas:Abbvie: Consultancy, Research Funding; Janssen: Research Funding; X4 Pharma: Research Funding; Ascentage Pharma: Research Funding; Mustang Bio: Consultancy, Honoraria; Sanofi: Research Funding; Cellectar Biosciences: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Research Funding; Acerta Pharma: Research Funding; Genentech: Research Funding; University of Texas MD Anderson Cancer Center: Current Employment. Orlowski:Bristol Myers Squibb, CARsgen Therapeutics, Exelixis Inc, Heidelberg Pharma, Janssen Biotech Inc, Sanofi, Takeda Pharmaceuticals USA Inc; Laboratory Research Funding: Asylia Therapeutics Inc, BioTheryX Inc, Heidelberg Pharma: Research Funding; Asylia Therapeutics Inc.: Current equity holder in private company, Patents & Royalties; DEM BioPharma, Inc., Karyopharm Therapeutics, Lytica Therapeutics, Meridian Therapeutics, Monte Rosa Therapeutics, Myeloma 360, Nanjing IASO Biotherapeutics, Neoleukin Corporation, Oncopeptides AB, Pfizer, Inc., Regeneron Pharmaceuticals, Inc., Sporos Bio: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; BioTheryX: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie Inc, Adaptive Biotechnologies Corporation, Asylia Therapeutics Inc, BioTheryX Inc, Bristol Myers Squibb, Karyopharm Therapeutics, Meridian Therapeutics, Monte Rosa Therapeutics, Nanjing IASO Biotherapeutics, Neoleukin Therapeutics, Oncopeptides, Pf: Membership on an entity's Board of Directors or advisory committees; Sanofi, Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding. Shpall:Zelluna Immunotherapy: Other: Scientific Advisor; Adaptimmune Limited: Other: Scientific Advisor; National Marrow Donor Program: Other: Board of Directors/Management; FibroBiologics: Other: Scientific Advisor; Axio Research: Current Employment, Other: Scientific Advisor. Qazilbash:BioLineRx: Research Funding; NexImmune: Research Funding; Janssen Pharmaceuticals: Research Funding; Angiocrine Bioscience: Research Funding; Amgen: Research Funding.