P955: carfilzomib in relapsed/refractory multiple myeloma patients: the real-life experience of emmy

Background: EMMY is a large-scale epidemiological study to assess the epidemiology and real-life management of multiple myeloma (MM). Proteasome inhibitors (PI), immunomodulators (IMID) and anti-CD38 (aCD38) provide broad solutions to treat patients. Following pivotal clinical trials, carfilzomib, a second-generation PI, is approved in relapsed/refractory (RR) MM. Its use in real-life setting can be assessed in EMMY. Aims: To assess the use of carfilzomib in RRMM patients in real-life conditions. Methods: EMMY is a descriptive, multicenter, national, non-interventional study conducted in 72 IFM (Intergroupe Francophone du Myélome, sponsor) sites in France. Any patient initiating treatment for MM over a 3-month annual observation period, is included, since 2017 This dynamic cohort has included approximately 900 patients each year (2765 patients included in 2019). Data are updated annually from hospital records. Patients receiving carfilzomib (K) for RRMM at inclusion or follow up were identified and classified by the regimens received. The median progression-free survival (mPFS), and median overall survival (mOS) were estimated per regimen and per treatment line. Results: 512 patients (18.5%) (median age 68.4 years (y), 20.5% ≥75y) received K for RRMM, 111 (21.7%) for a second (L2), 97 (18.9%) a third (L3) and 304 (59.4%) a fourth or more (L4+) line. K was used in a double regimen with dexamethasone (Kd) in 232 patients (45.3%) and in a triple regimen either with an IMID (K-IMID) in 198 (38.7%) patients or with other agents in 82 patients (16%) (K-aCD38 for 35 (6.8%), K-alkylant for 27 (5.3%) and K-venetoclax for 19 (3.7%) patients). 25.4% patients (62/244) were at high cytogenetic risk. K-IMID was used in patients of 66,8y, with an ECOG ≥ 2 for 20.8%, and comorbidities (≥ 1) for 24.3% including 3% of cardiovascular diseases. K-IMID was used in L2 (42.9%), L3 (21.7%) and L4+ (35.4%). 63.1% were priorly exposed to lenalidomide (len) of which 35,9% were refractory. K was combined with len in 144 (28,1%) and with pomalidomide (pom) in 54 (10,5%) patients. The use of K-pom increased over years: 14,4% in 2018, 28,2% in 2019, 73,9% in 2020. mPFS was overall 10.4 months (m) 95%CI [7.3; 14.7]; it was 23m 95%CI [14.7; -] in L2, 6.2m 95%CI [1.3; 12.2] in L3 and 7.1m 95%CI [4.6; 9.2] in L4+. mOS was not reached in L2, L3 or L4+. Kd was used in patients of 70.1y, with an ECOG ≥ 2 for 31.3% and comorbidities for 29.3%. 93.5% were priorly exposed to len of which 66.4% were refractory. Kd was used in L2(6%), L3 (17.2%) and L4+ (76.8%). mPFS and mOS were 4.4m [3.7; 5.8] and 19.5m [13.7; 22.3] in L4+. K-aCD38 was used in patients of 63.5y, with an ECOG ≥ 2 for 10%, and comorbidities (≥ 1) for 37.1%. 91.4% were priorly exposed to len including 45.7% len-refractory. K-aCD38 (33/35 with daratumumab) was used in L2 (31.4%), L3/L4 (35.7%) and L5+ (22.9%). mPFS and mOS (all lines included) were 6m [3.8; 15.1] and 21.3m [16.9; -]. K-alkylant (5/27 with bendamustine, 22/27 cyclophosphamide) and K-venetoclax were used in older patients (71.8y and 70.4y) and in L4 or L5 for >80% of them. More than 90% were pre-exposed to len including 65% of len-refractory patients. K discontinuation was recorded for 63.4% of patients for progression in 44% and adverse event in 11.7% of them. Summary/Conclusion: The EMMY study shows that carfilzomib is used in many combinations in extended real-life settings compared to pivotal clinical trials including older patients, largely-exposed to lenalidomide and at advanced disease. The use of lenalidomide in early stages has led to a shift in the management of RRMM patients with carfilzomib.