Background: There is contradictory data regarding the prognostic impact of additional copy numbers of chromosome 1q (1q+) on the outcomes of newly diagnosed multiple myeloma (NDMM) patients, and there is scarce data in the context of autologous stem cell transplantation (autoSCT). In this report, we studied outcomes of NDMM patients with 1q+ who received induction with contemporary anti-myeloma agents, followed by autoSCT and post-transplant maintenance therapy.

Methods: We conducted a retrospective single-center chart review analysis of adult NDMM patients with 1q21 gain or amplification (3 or ≥4 copies of 1q, respectively; 1q+) detected by fluorescence in situ hybridization (FISH) that received autoSCT between 2008-2018. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints.

Results: 213 NDMM patients with 1q+ were included in the analysis, with a median age of 62.5 years and 53% were male. Overall, 169 (79%) patients had 1q gain, while 44 (21%) patients had 1q amplification. The most commonly used induction and conditioning regimens were bortezomib, lenalidomide, and dexamethasone (VRD) (41%) and melphalan (77%), respectively (Table 1). At day 100 after autoSCT and at best post-transplant response, 78% and 87% of patients achieved ≥VGPR, 34% and 56% achieved CR, 38% and 50% achieved MRD negative ≥VGPR, respectively. The median PFS and OS for the entire cohort were 35.5 months and 81.4 months, respectively. 1q amplification was associated with inferior PFS compared to 1q gain (HR=2.03, 95% CI 1.36-3.03, p<0.001; Figure 1).

On multivariable assessment (MVA) for PFS, MRD negative >VGPR before autoSCT and at day 100 post-transplant [(HR=0.56, 95% CI 0.36-0.86, p=0.009) and (HR=0.64, 95% CI 0.44-0.94, p=0.022), respectively] were associated with better PFS, whereas 1q amplification was associated with inferior PFS (HR=1.94, 95% CI 1.29-2.92, p=0.001). On MVA for OS, R-ISS stage III (HR=4.08, 95% CI 1.07-15.50, p=0.039) was associated with inferior OS, whereas achieving MRD negative >VGPR at best post-transplant response was associated with superior OS (HR=0.45, 95% CI 0.24-0.85, p=0.014).

Notably, the percentage of cells with 1q+ was not associated with PFS nor with OS, both when evaluated as a continuous variable and when evaluated as a categorical variable using thresholds of either 30% or 50%. The presence of additional high-risk cytogenetic abnormalities did not adversely affect survival outcomes.

Conclusions: Patients with NDMM and 1q+, especially 1q amplification, have poor survival outcomes, despite the use of contemporary induction regimens, upfront autoSCT and post-transplant maintenance. These patients may benefit from novel treatment modalities, such as CAR-T and bispecific antibodies, earlier in their disease course.

Bashir:Stemline: Research Funding; Acrotech: Research Funding; Pfizer: Research Funding; GSK: Research Funding. Srour:Orca Bio: Research Funding. Saini:GSK: Research Funding; Panbela Theraputics: Research Funding. Lin:Takeda: Patents & Royalties, Research Funding. Nieto:Affimed: Research Funding; Astra Zeneca: Research Funding; Secura Bio: Research Funding. Kebriaei:Pfizer: Consultancy, Honoraria; Jazz: Consultancy, Honoraria. Lee:Genentech: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Sanofi: Consultancy; Pfizer: Consultancy; Monte Rosa Therapeutics: Consultancy; Takeda Pharmaceuticals: Consultancy, Research Funding; Allogene Thereapeutics: Consultancy; Regeneron: Consultancy, Research Funding; Amgen: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding. Patel:Takeda: Consultancy; AbbVie; Allogene Therapeutics, Inc.; Arcellx; Bristol Myers Squibb/Celgene Corporation; Cellectis; Janssen Pharmaceuticals, Inc.; Nektar Therapeutic; Poseida Therapeutics; Precision BioSciences, Inc.; and Takeda Pharmaceuticals U.S.A., Inc.: Research Funding; AbbVie; Arcellx, AstraZeneca; Bristol Myers Squibb/Celgene Corporation; Caribou Science; Cellectis; Curio Bioscience; Genentech; Janssen Pharmaceuticals, Inc.; Karyopharm; Legend Biotech; Merck & Co., Inc.; Oncopeptides; Pfizer; Precision BioSciences: Consultancy. Thomas:Bristol Myers Squibb, Janssen Pharma Genentech, X4 pharma, Cellectar Biosciences, Ascentage Pharma: Research Funding; Genentech: Research Funding; Abbvie, Cellectar Biosciences: Consultancy; X4 pharma: Research Funding; Cellectar Biosciences: Consultancy; Cellectar Biosciences: Research Funding; Janssen Pharma: Research Funding; Ascentage Pharma: Research Funding. Orlowski:Asylia Therapeutics, BioTheryX Inc., Heidelberg Pharma: Other: Laboratory Research Funding, Research Funding; BMS/Celgene Corporation, CARsgen Therapeutics, Exelixis Inc., Heidelberg Pharma, Janssen Biotech Inc., Sanofi/Genzyme, Takeda Pharmaceuticals USA Inc.: Other: Clinical Research Funding, Research Funding; AbbVie, Adaptive Biotech, Asylia Therapeutics, Inc., BioTheryX, Bristol-Myers Squibb Pharmaceuticals, Karyopharm Therapeutics, Meridian Therapeutics, Monte Rosa Therapeutics, Nanjing IASO Biotherapeutics, Neoleukin Corporation, Oncopeptides AB, Pfizer, In: Consultancy, Honoraria; Asylia Therapeutics: Current equity holder in private company, Patents & Royalties. Shpall:Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Celaid Therapeutics: Membership on an entity's Board of Directors or advisory committees; Axio: Membership on an entity's Board of Directors or advisory committees; Fibrobiologics: Membership on an entity's Board of Directors or advisory committees; Navan: Membership on an entity's Board of Directors or advisory committees; Affimed: Other: License agreement; Syena: Other: License agreement; Takeda: Other: License agreement; NY Blood Center: Membership on an entity's Board of Directors or advisory committees. Champlin:Arog: Consultancy; Actinium Pharmaceuticals: Consultancy; Omeros: Consultancy; Orca Bio: Consultancy; Johnson & Johnson/Janssen: Consultancy; Kadmon: Consultancy; Cell Source: Research Funding; Takeda Corporation: Patents & Royalties. Qazilbash:Amgen: Research Funding; Bioline: Other: Advisory board; Angiocrine: Research Funding; NexImmune: Research Funding; Janssen: Research Funding.

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2023
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