Outcomes of lenalidomide retreatment with novel triplet regimens in patients with multiple myeloma progressing on lenalidomide‐based maintenance therapy

Several phase III randomised studies have validated the use of novel three-drug regimens with lenalidomide (LEN) and dexamethasone (Rd) in combination with carfilzomib (ASPIRE), 1 elotuzumab (ELOQUENT-2), 2 ixazomib (TOUR-MALINE-MM1), 3 and daratumumab (POLLUX) 4 in relapsed and/or refractory multiple myeloma (RRMM) with one or more lines of prior therapy. These pivotal studies led to the regulatory approval of these triplet regimens, although nota-bly, these studies excluded patients who were LEN-refractory, as the control arms in these studies were treated with Rd. In practice though, most patients with myeloma at first relapse for which these LEN-based triplets have been approved are progressing on low-dose maintenance LEN therapy, although their outcomes have not been well characterised in randomised clinical trials that excluded such patients. In the present study, we report the outcomes of LEN retreatment as part of novel LEN-based triplets in patients with RRMM progressing on LEN-based maintenance therapy in a single-centre retrospective analysis. Eligible patients included patients with myeloma progressing on LEN-based maintenance therapy between January 1, 2015 and June 30, 2018 at the University of Texas MD Anderson Cancer Center (UTMDACC) after autologous stem cell transplant (ASCT) who were then treated with a LEN-based triplet. Post-main-tenance LEN-based triplet regimens included Rd in combination with bortezomib (VRd), carfilzomib (KRd), elotuzumab (ERd), ixazomib (IRd), and daratumumab (DRd). Full study methods are detailed in Data S1.