P47 real-world data of attrition rates by subsequent lines of therapy in multiple myeloma patients treated in a tertiary care italian centre

Despite therapeutic progress leading to a significant improvement of outcomes, most Multiple Myeloma (MM) patients relapse and require subsequent lines of therapy (LOTs). Nevertheless, several cross-sectional real-life studies demonstrated that many patients were not able to receive subsequent LOTs [Raab MS et al, Br J Haematol 2014; Raab MS et al, Br J Haematol 2019; Coriu D et al, Pol Arch Int Med 2018]. Retrospective longitudinal studies reported that Attrition Rates (ARs), defined as the rate of patients who fail to receive a subsequent LOT for any reasons, like death or lack of fitness, was high and increasingly across all LOTs [Fonseca R et al, BMC Cancer 2020; Steinmetz T et al, Oncol Res Treat 2021]. In order to verify these data in an Italian real life setting, we conducted a retrospective observational monocentric study on treatment patterns and ARs across all LOTs in newly diagnosed MM patients recorded in our database from 2011 to 2021, evaluating treatment patterns of each LOT; AR across LOTs; ORR, CR and survival rates of each LOT and potential factors affecting AR by logistic regression analysis. We analyzed 413 patients with a median age of 69 years (range 30-93), 61.5% older than 65 years, with ECOG PS ≥ 2 in 22% and 118 (30%) who had more than 2 comorbidities. R-ISS stage 2-3 and renal failure were detected in 74% and 18% of patients respectively. Median follow-up was 48.7 months (range 6-140). In LOT-2 the most frequently used regimens were lenalidomide (L)-based (35%) and bortezomib (B)-based (33%). In LOT-3 patients received mainly L- (21.5%), pomalidomide (P)- (20.5%) and B-based (18%) regimens whereas both carfilzomib (K)- and antiCD38 MoAbs-based regimens were given to 14% of patients. In LOT-4 and LOT-5 P-based regimens were the most used (26.5% and 32%, respectively). Rate of patients receiving therapy from LOT1 to LOT-5 are summarized in the Table. AR was found to be 25% in LOT-1, 39%, 37% and 39% across LOT-2, LOT-3 and LOT-4, respectively, and 50% in subsequent LOTs. Moreover, we examined differences in AR by time, finding that patients who did not receive a LOT-2 were 43/71 (≤2018) and 28/71 (>2018). So, AR was 60.5% in the cohort before 2018 vs. 39.5% after 2018. In univariate analysis age >65 years, ISS 2-3, > 2 comorbidities, no transplant, response < VGPR and no maintenance were significantly associated with higher AR but regression analysis selected only age > 65 years [OR 7.4 (3.3-16.5)] and > 2 comorbidities [OR 2.5 (1.5-5.6)] as factors affecting AR. Of note, comparing transplant eligible with not transplant eligible patients, AR was 8% vs 42% (p<0.0001) in LOT-2, 16% vs 60% (p<0.0001) in LOT-3 and 29% vs 50% (p=0.053) in LOT-4, respectively. ORR and CR rates, TTNT and OS throughout the lines of therapy are reported in the Table. In our real-life experience a quarter of patients was not able to receive a LOT-2 and a LOT-3 after a first and a second relapse, respectively. In the subsequent relapses ARs were higher sinceabout a third of patients did not receive a LOT-4 and a LOT-5 and half of patients did not receive further lines. However, AR seems to be globally lower than that described by cross-sectional studies. We found fit and young patients are able to receive many LOTs, whereas older patients and/or patients with comorbidities are not. But in recent years this scenario is also improving for older patients, reinforcing the idea to continue new drugs experimentation also in the later LOTs.