Lenalidomide: Based maintenance after autologous hematopoietic stem cell transplant for patients with high-risk multiple myeloma.
Authors: Pasvolsky Oren , Milton Denai R. , Rauf Mikael , Tanner Mark R. , Bashir Qaiser , Srour Samer Ali , Saini Neeraj , Ramdial Jeremy L , Nieto Yago , Lee Hans C. , Patel Krina K. , Kebriaei Partow , Thomas Sheeba K. , Weber Donna M. , Orlowski Robert Z. , Shpall Elizabeth J. , Champlin Richard E. , Qazilbash Muzaffar H. 
Published: June 2022

e20024

Background: Maintenance therapy with single-agent lenalidomide (Len) after autologous hematopoietic stem cell transplantation (autoHCT) for multiple myeloma (MM) is associated with improved progression-free survival (PFS). However, patients with high-risk chromosomal abnormalities may need a more intense regimen. We hypothesized that adding another anti-myeloma drug to Len would lead to improved outcomes. Methods: We conducted a retrospective single-center chart review of adult MM patients with high risk cytogenetic abnormalities that received autoHCT between 2008-2018, followed by Len-based maintenance therapy. High risk cytogenetics were defined as del17p, t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization. We divided patients into those who received either single-agent Len maintenance (Len-only) or Len-based combinations (Len-combo). We compared PFS, overall survival (OS), non-relapse mortality (NRM), day 100 and best post-transplant responses, and minimal residual disease (MRD) status between groups. We performed sensitivity analyses using inverse probability weights to correct for potential bias due to nonrandomization of the two groups. Results: A total of 231 patients with HRMM were included in our analysis, with a median age of 62.4 (range 33.5-79.9) years, and 55% were male. There were 153 patients in the Len-only group and 78 in the Len-combo group. Len-combo regimens were either doublets (Len with dexamethasone [dex: n = 10], elotuzumab [n = 28] or ixazomib [n = 14]) or triplets (Len with bortezomib/dex [n = 10], ixazomib/dex [n = 10] or carfilzomib/dex [n = 6]). More patients in the Len-combo group had >2 high risk cytogenetic abnormalities compared to the Len-only group (32% vs. 12%: p < 0.001). Busulfan + melphalan (Bu-Mel) conditioning was used in 12% vs. 18% in Len-only vs. Len-combo groups (p = 0.32). The final best response post-transplant of sCR/CR was 50% in the Len-only group vs. 54% in the Len-combo group (p = 0.72). Median follow up was 40.7 and 35.3 months, with Len-only and Len-combo, respectively. Median PFS and OS for all patients were 25.5 and 82.6 months, respectively. There was no significant difference in PFS (HR: 1.01, CI: 0.71-1.44, p = 0.94) or OS (HR: 0.84, CI: 0.49-1.43, p = 0.52) between groups. Similarly, there was no difference in outcomes between the groups whether they received conditioning with melphalan-only or Bu-Mel. However, for patients with HR cytogenetic abnormalities other than 1q+ there was a trend towards better PFS with Len-combo (HR 0.59, CI 0.32-1.09, p = 0.09), without a difference in OS (HR: 0.79, CI: 0.37-1.65, p = 0.53). Conclusions: In this single center retrospective analysis, intensification of post-transplant Len maintenance did not show an improvement in outcomes for HRMM patients. However, there was a trend towards improved PFS in patients with HR abnormalities other than 1q+.