First-Line Daratumumab-Based Regimens in Multiple Myeloma Patients Aged 65-70 Years: A Pilot Real-World Study on Efficacy and Safety

INTRODUCTION. Daratumumab is now approved in Italy for first line treatment in patients with Multiple Myeloma (MM) both eligible or ineligible for autologous stem cell transplantation (ASCT), with three different combinations available, namely DVTD (plus Bortezomib + Thalidomide + Dexamethasone) which is part of a program that includes also ASCT, and DRD (plus Lenalidomide + Dexamethasone) and DVMP (plus Bortezomib + Melphalan + Prednisone) which are given continuously until progression. In patients aged 65 to 70 years there are no comparative protocols conducted to verify the differences in terms of results and toxicity of therapeutic programs that include or not ASCT, therefore in real life the choice of the appropriate regimen in this particular cohort of patients is based on less standardized criteria. To investigate this matter, we retrospectively analyzed data from a consecutive cohort of 40 newly diagnosed MM patients from two Institutions, aged 65-70 years and treated outside of clinical trials with different Daratumumab-based combinations according to clinical characteristics and to physician's choice. MATHERIAL & METHODS AND RESULTS. In our study there were 23 males and 17 females, median age 69 years (range 65-70) distributed as follows: 14 DVTD (median 66, range 65-69), 23 DRD (median 69, range 65-70), and 3 DVMP (69, 69 and 70 years, respectively). All patients had symptomatic MM requiring therapy. Fitness was evaluated with IMWG score, and there were G0=10, G1=19, G2=8, and G3=3. According to eligibility to ASCT, median IMWG score was 0 (0-2) for DVTD group, and 1 (0-3) for DRD/DVMP group. Median of comorbidities was 2 (1-4) in DVTD group, all in good compensation, and 3 (1-6) in DRD group; in the DVMP group there were 2 patients with acute renal insufficiency, while the last one had 5 different comorbidities. FISH rates were standard, high risk or not done/failed in 40%, 25% and 35% of the whole population. In particular, 8/10 high patients were in DRD/DVMP subgroup. Overall response rate of the whole population was 90% (36/40). More in detail, rate of complete + very good partial remission (CR + VGPR) was 78% for DVTD patients and 65% for DRD/DVMP patients. One DVTD patient was refractory and proceeded to second line treatment, while there were 3 early deaths in DRD group due to cardiovascular events. Toxicity and supportive therapy were recorded and main results are reported here. Documented infections or FUO were present in 3/14 (23%) and 13/26 (50%) in DVTD and DRD/DVMP group, respectively. There were 5 cases of thrombosis (all in DRD patients), and 9 cases of grade ≥2 peripheral neuropathy (all in DVTD patients). Use of Epoietin was necessary in 3/14 (23%) and 16/26 (62%) in DVTD and DRD/DVMP group, respectively, and red blood cell transfusions were needed in 8 patients (1 DVTD and 7 DRD/DVMP). Finally, during therapy and/or follow up use of intravenous IgG was needed in 6/40 patients (15%): 4 DRD/DVMP and 2 DVTD. Of note, 6/13 DVTD responding patients (46%) did not proceed to ASCT for refusal (2), subsequent frailness (2), no mobilization (1), and early relapse after mobilization (1). After a median follow up of 15 months (range 1-41), Progression Free Survival (PFS) and Overall Survival (OS) are not reached in the whole population and in both subgroups (p=0.68 and 0.2, respectively). Estimated PFS at 15 months are 85.9% (whole population), 84.6% (DVTD) and 86.5% (DRD/DVMP). Relapse was observed in 1/13 (8%) patients in DVTD group, as mentioned earlier, and in 4/23 (17%) in DRD/DVMP group. At the moment of writing, 6 patients have died (in 1 case for MM) and they are all from DRD/DVMP group. DISCUSSION. In our cohort, younger or older age and frailness are the major factors determining the choice of using ASCT as part of the first line therapeutic program in 65-70 years old MM patients. Significant toxicity is more present in the DRD/DVMP, but this may be primarily affected by the unfavourable clinical characteristics of patients more than by the type of regimen. A significant rate of DVTD patients actually did not undergo ASCT, and this is not observed in younger patients. OS and PFS do not show significant differencies in the two groups, but this needs to be confirmed with longer follow up. Given the importance of the subject, further analysis is needed and our intent is to broaden the cohort of patients including other Institutions.

Palmieri:Amgen: Honoraria; GSK: Honoraria; Janssen: Honoraria; Sanofi: Honoraria. Pane:GSK Incyte Amgen BMS Janssen Jazz Novartis Pfizer: Speakers Bureau; GSK Incyte: Consultancy.