Lenalidomide Maintenance in Multiple Myeloma: A Retrospective, Nationwide, Real-World Study

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Lenalidomide maintenance (LM) has shown progression-free and overall survival benefit in clinical trials and is the recommended standard of care in patients with newly diagnosed multiple myeloma (MM) after high-dose melphalan and autologous stem cell transplantation (HDM-ASCT). However, reports of the use of LM in a real-world setting are limited. In Denmark, LM has been approved since August 2019 and is publicly funded. Aims: To describe the real-world use patterns, efficacy, and adverse effects of LM. Methods: Patients with newly diagnosed MM fulfilling the CRAB or slim-CRAB criteria treated with their first HDM-ASCT between 1. January 2019 and 1. March 2022 were included in the study and followed until data cut-off in September 2022. Patients were identified from the local transplantation registers. Baseline clinical characteristics were acquired from the Danish MM Registry. Medical doctors at the respective departments reviewed the electronic records of all patients retrospectively. Results: Patient characteristics We identified 384 patients who fulfilled the inclusion criteria. The median age was 60.7 years, 57.3% were male, 31.8% had anemia, 11.6% had renal failure, and 19.3% had hypercalcemia at diagnosis. FISH was available in 81.9% of patients, and 23.5% of these had high-risk cytogenetics defined as the presence of t(4;14), t(14;16) or del17p. Initial treatment Bortezomib-lenalidomide-dexamethasone (VRD) and cyclophosphamide-bortezomib-dexamethasone were used as induction in 57.8%, and 32.6% of patients, respectively. After HDM-ASCT, the VGPR or better rate was 83%. Consolidation therapy was used in 22.3% and tandem HDT-ASCT in 3.7% of patients. Maintenance From HDM-ASCT, the median time to initiation of LM was 4.1 months and median follow-up was 22.5 months. LM was used in 252 (65.6%) of patients. The most frequently used dosing was 10 mg (92.8%) for 21 days (88.8%). Renal failure was more prevalent in patients not treated with LM (16.7 vs 10.4%) while high-risk cytogenetics were more prevalent in patients treated with LM (26.1% vs 18.1%); other baseline characteristics were similar. Lenalidomide was dose-reduced in 31.2% of patients; the main reasons for this were cytopenias (54.5%), fatigue (18.2%), and rash (9.1%). The 12 months discontinuation rate was 31.9% (Figure 1a) and a total of 99 (39.4.%) patients discontinued LM; most frequently due to toxicity (45.5%) and progressive disease (38.4%). The main toxicities leading to discontinuation were cytopenias (28.9%), fatigue (26.7%) sensory neuropathy (17.8%), and diarrhea (11.1%). Using cox regression with maintenance as a time dependent variable, LM was not associated with better PFS in univariate analysis; HR 0.92 (0.60-1.42). Results were similar using landmark analysis (Figure 1b). Overall survival data were not mature. Therapy at relapse 85 patients received a subsequent line of therapy. The most frequently used combination in patients not treated with LM (n=35) was daratumumab-lenalidomide-dexamethasone (DRD, 54.5 %), while it was DRD (25.5 %) and daratumumab-bortezomib-dexamethasone (23.4 %) in patients treated with LM (n=50). The VGPR or better rate achieved with the subsequent line of therapy was 33.3% in patients who had received LM vs 54.8% in patients who had not, p=0.1. Summary/Conclusion: In this retrospective, nationwide, real-world study including 384 patients we found that LM is used in two-thirds of patients with MM after HDM-ASCT. Approximately one third of patients treated with LM discontinues this treatment within the first year, mainly due to toxicity. After a median follow-up of 22.5 months from HDM-ASCT we did not observe PFS benefits with LM.Keywords: Maintenance, Immunomodulatory thalidomide analog, Multiple myeloma, High dose therapy