Lenalidomide plus Dexamethasone Combination as First-Line Oral Therapy of Multiple Myeloma Patients: A Unicentric Real-Life Study

SIMPLE SUMMARY: For a few years, lenalidomide plus dexamethasone (Len/Dex) has become a new standard of care for newly diagnosed multiple myeloma (NDMM) patients who are not eligible for autologous stem cell transplantation. The FIRST trial showed that continuous therapy with Len/Dex is superior in progression-free survival (PFS) and overall survival (OS) compared to fixed treatment or triplet, leading to approval for NDMM. The knowledge of the safety and efficacy of Len/Dex in frail and ultra-frail patients is limited. This study evaluates the Len/Dex combination, correlating it with the prognostic impact of different variables on PFS and OS. Our real-world data report that an elderly and frail population, rarely included in randomized clinical trials, may benefit from Len/Dex combination, with an incidence of adverse events that is inferior to pivotal trials. Thus, the oral and self-administering outpatient Len/Dex scheme is a considerable treatment choice in patients with high ECOG or age >75 years old. ABSTRACT: Based on the results obtained in clinical trials, the use of the combination of lenalidomide and dexamethasone (Len/Dex) has become a potential therapeutic choice for newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation. This study evaluated 89 frail NDMM patients treated with first-line oral association. At the last follow-up, 34 out of 89 patients (38.2%) were alive, and 22 were still in treatment with Len/Dex. Among 73 evaluable patients who received at least two cycles, the overall response rate was 71% (N = 52). The disease control rate, defined as any level of clinical response to therapy, occurred in 71 patients (97%). We reported one or more adverse events of grade 3 or 4 (G3/4) in 65.2% (N = 58) of patients, with a prevalence of hematological toxicity (24 patients), leading to an overall discontinuation of treatment in two cases. In univariate analysis, high ISS, high serum β2-microglobulin, and creatinine clearance <30 mL/min negatively impact OS, while the depth of response positively impacts OS. Moreover, G3-4 anemia, ISS, frailty score, and ECOG negatively impacts PFS. In conclusion, elderly and more frail patients benefit from the Len/Dex combination also in the era of monoclonal antibodies, ensuring an increased PFS and OS in patients where the therapeutic choice is often limited and usually not very effective.