P20 lenalidomide maintenance after vtd induction and autologous stem cell transplantation: preliminary results of a real-life study including 389 patients

According to 2021 ESMO guidelines, treatment of newly diagnosed (ND) transplant eligible (TE) Multiple Myeloma (MM) patients is settled by an induction phase followed by single or tandem autologous stem cell transplantation (ASCT) and Lenalidomide (Len) maintenance. Before the recent approval of daratumumab-bortezomib-thalidomide-dexamethasone (D-VTD) regimen, VTD induction followed by ASCT and Len maintenance was the standard of care in Italy for ND TE MM patients, however no single perspective trial evaluated this combination overall. In this context, the aim of this real-life study was to evaluate the efficacy and the safety of Len maintenance after VTD plus ASCT in ND TE MM patients. The study cohort included 389 patients (median age 60 years) followed in 17 referral centers. Baseline features included ISS III in 67/352 cases (19%), R-ISS III in 28/296 cases (9.5%) and R2-ISS IV in 21/254 cases (8.3%). FISH analysis was available in 306 patients and 50 of them (16.3%) displayed high risk (HR) alterations [including t(4;14), t(14,16) and del17p]. Among the 256 standard risk patients, information about 1q status was available for 230 of them, with 43 patients harboring +1q abnormalities (18.7%). All patients received VTD induction (median number of cycles 4) and single or tandem ASCT was performed in 60.9% and 39.1% of cases, respectively. A median number of 21 cycles of Len maintenance was administered. Complete response (CR) and stringent CR (sCR) rates before starting Len were 28.3% and 15.9%, respectively (overall 44.2%) and increased with maintenance to 36.2% and 19.8%, respectively (overall 56%). Most importantly 2 years CR and sCR rates in evaluable patients were superimposable (38.6% and 22.3% respectively, 60.9% overall). Ninety-seven patients (24.9%) discontinued treatment, mostly due to progressive disease (83/97, 85.6%). Toxicities were mostly hematological with neutropenia found in 48.8% of cases (grade 3-4 in 20.3%), followed by thrombocytopenia and anemia in 22.9% and 18%of cases, respectively (grade 3-4 in 2.8% and 1.8% of cases, respectively). Non hematological adverse events were primarily gastrointestinal (26.5%, grade 3-4 in 2.6%) and infections (23.4%, grade 3-4 in 3.6%) while skin related disorders affected 9% of patients. With a median follow up of 26 months, the 2 years PFS and OS from starting maintenance were 79.5% and 96.5%, respectively. No significant PFS differences were found according to age (>65 years vs < or =65 years, p=0.6581) or ASCT (single vs tandem, p=0.4528). Patients with low-risk disease including ISS I and R-ISS I showed improved PFS as compared to patients with ISS >I and R-ISS >I (2y PFS 86.8% vs 73.3%, p=0.029 and 91.9% vs 67.6%, p=0.0002. respectively). By R2-ISS, low risk disease (R2-ISS I) confirmed a better outcome as compared to R2-ISS II-III (2y PFS 93.3% vs 69.7%, p=0.0004) and to R2-ISS IV (2y PFS 45%, p<0.0001). Finally, considering cytogenetic risk status, standard risk patients displayed a significantly prolonged PFS as compared to high-risk patients (2y PFS 83.1 % vs 52.7%, p<0.0001) and an improved although not significant outcome than patients harboring isolated +1q (2y PFS 74.4%, p=0.077) (Figure 1). To our knowledge, this is the first study evaluating the safety and efficacy of Len maintenance after VTD plus ASCT. Our results provide evidence that patients with clinical and biological low risk disease benefit the most from Len maintenance with a favorable safety profile.