LENALIDOMIDE AND LOW-DOSE DEXAMETHASONE (RD) AS FIRST LINE TREATMENT OF NEWLY-DIAGNOSED MULTIPLE MYELOMA PATIENTS NOT ELIGIBLE TO STEM CELL TRANSPLANTATION: REAL LIFE ITALIAN EXPERIENCE

Background: Lenalidomide (Len) and low-dose Dexamethasone (dex) (Rd) in continuous is a new standard of care for elderly newly-diagnosed multiple myeloma (NDMM) patients (pts), showing a remarkable efficacy with a good toxicity profile. Aims: This is a retrospective, multicentric study conducted in Italy with the aim of evaluating efficacy and tolerability of Rd in a real-life population. Methods: Thirty-seven centers were involved and data of 509 pts are available. Pts were considered eligible for the study when completing at least 2 cycles of Rd regimen. Data about pts characteristics, response to therapy and safety were collected. Results: Median age was 77 years (range 40-92), ECOG PS was ≥2 in 36.6% and creatinine clearance was < 50 ml/min in 36.9% of pts. Based on IMWG Frailty score, 18.5, 29.2 and 52.3% of pts were scored as fit, unfit and frail. ISS was I, II and III in 27.5, 39.1 and 33.4% while R-ISS was I, II and III in 32.2, 41.3 and 26.5% of pts. FISH data were available in 48.7% of pts; t(4;14), t(14;16), del(17p) and amp(1q) were respectively found in 8.1%, 4.6%, 5.7% and 35.2%. Extramedullary disease (EMD) was documented in 9.4% of pts. After a median follow-up of 14 months, most pts was still on treatment (55.4%); the median number of administered cycles was 11 (range 2-40). Overall response rate (ORR, ≥PR) was 75.7% with 34.5% of pts obtaining at least a VGPR. Clinical Benefit Rate (CBR, including minimal responses) was 84.3%. Responses were rapid with median time to first (≥PR) and best response respectively of 2.5 (range 1-19) and 6.9 (1-30) months. Median OS and PFS were not reached with 12m and 24m OS of 86.5 and 73.7% and 12m and 24 m PFS of 73.2 and 53.3%. When comparing pts harbouring high risk FISH (i.e. t(4;14), t(14;16) and/or del(17p)) to pts without these abnormalities, ORR was 59.5 vs 79.6% (p = 0.009), without significant difference in terms of 1 year OS and PFS as far (respectively 82.1 vs 91.1%, p = 0.74; 65.3 vs 76.9%, p = 0.41). Dose reduction of Len or dex was required respectively in 23.2% and 22.2% of pts and 39.3% needed cycle delay for adverse events (AEs); 13.1% of pts definitively discontinued Rd for toxicity while 20.8% for progression. Grade 3-4 (G3-4) AEs occurred in 49.9% of pts with 31.4 and 33.6% having at least an hematological or extra-hematological G3-4 AE. In particular, 17.4 and 16.3% of pts had severe neutropenia and anemia while the most common non-hematological AEs were infections (27.2%, G3-4 11%), mainly involving respiratory tract (68.8%). Gastroenteric and cutaneous AEs were quite common (21.4 and 18.9%), but in the vast majority were mild. G3-4 asthenia was present in 21.8% of pts. Although 99% of pts was given antithrombotic prophylaxis, mainly with low-molecular wheight heparin, 8.5% had a thromboembolic event, 37.8% were severe. G-CSF and EPO analogs were required in 26.1 and 27.7% of pts. At the time of analysis, 123 pts (24.2%) had already progressed; 97 pts (78.8% of patients with progression) received a second line therapy, with an ORR of 55.7%. Most used salvage regimens were Bortezomib/ Dexamethasone (53.6%) and Daratumumab/Bortezomib/Dexamethasone (21.6%) while 7.1% received only palliation. Summary/ Summary/Conclusion: Real-life data in elderly NDMM pts treated with Rd confirm similar efficacy and tolerability registered in randomized clinical trials. Given the availability of FISH data in a large proportion of pts, it will be interesting to evaluate the impact of high risk chromosomal abnormalities after longer follow-up.