Real-World Treatment Patterns of Patients Initiating Third-Line Therapy in Relapsed or Refractory Multiple Myeloma in Europe

Objectives: Real-world (RW) evidence can provide valuable insights into clinical practice and help identify and address unmet medical needs. We report RW treatment utilisation in patients from European data sets who initiated third-line (3L) treatment for relapsed/refractory multiple myeloma (RRMM). Methods: This retrospective, noninterventional analysis used claims data from the German AOK PLUS health insurance fund and Italian Local Health Units (2012–2020). Patients initiating 3L treatment from 2016–2020 (index) were identified using an algorithm based on prescription and procedure codes. New lines of treatment were defined as introduction of a new agent not part of the prior line. Agents given ≤30 days of start of the line defined the regimen. Retreatments after >6 months of discontinuation were considered a new line. Baseline characteristics and treatment patterns were reported. Results: Patients were identified from Germany (N=276) and Italy (N=289) (Table). Baseline characteristics were similar between countries. Prior to 3L treatment, immunomodulatory imide drug (IMiD) use was higher (74% vs 56%) and proteasome inhibitor (PI) use was lower (52% vs 96%) among patients in Italy versus Germany. At 3L, the proportion of double-class exposed patients in Italy was lower versus Germany (33% vs 52%). In Germany, common first-line (1L) regimens were bortezomib (BORT) + dexamethasone (DEX; Vd, 46%), BORT + melphalan (MEL) + prednisone (PRED; VMP, 14%), and Vd + cyclophosphamide (CyBORD, 8%). The most common second-line (2L) treatment regimens were lenalidomide (LEN) + DEX (Rd, 30%), Vd (11%), and carfilzomib (CFZ) + Rd (KRd, 8%). By 3L, 95% and 54% of patients had received prior BORT- and LEN-based regimens, respectively. In 3L, combinations were often LEN- and/or CFZ-based with daratumumab (DARA) monotherapy and pomalidomide + DEX (Pd) also contributing ~4% each (Table). Table - Baseline (12 months) and treatment characteristics in patients with relapsed/refractory multiple myeloma who initiated 3L treatment Characteristic Germany(N=276) Italy(N=289) Male, n (%) 139 (50) 141 (49) Median age at index (interquartile range), years 75 (65–80) 73 (66–79) Median time since diagnosis (range), years 2.7 (0.4–7.4) 2.1 (0.3–6.7) Year of 3L treatment initiation, n (%) 2016 58 (21) 35 (12) 2017 57 (21) 48 (17) 2018 57 (21) 52 (18) 2019 54 (20) 80 (28) 2020 50 (18) 74 (26) Prior treatment (excluding maintenance), n (%) PI 264 (96) 151 (52) Immunomodulatory drug 154 (56) 213 (74) anti-CD38 30 (11) 13 (4.5) LEN + PI-exposed and POM-naive 135 (49) 61 (21) Double-class exposed 144 (52) 96 (33) Triple-class exposed 15 (5) 8 (3) Stem cell transplant 75 (27) 43 (15) 3L treatment regimens ≥4% in either country, n (%) Rd 53 (19) 79 (27) KRd 27 (10) 11 (4) Kd 22 (8) 9 (3) DRd 22(8) 15 (5) DVd 18 (7) ≤3a Pd 11 (4) 35 (12) DARA 11 (4) 0 (0) Melphalan + prednisone 0 (0) 21 (7) aNot issuable due to anonymisation regulations.Rd, LEN + DEX; KRd, CFZ + LEN + DEX; Kd, CFZ + DEX; DRd, DARA + LEN + DEX; DVd, DARA + BORT + DEX; Pd, POM + DEX.3L, third-line; BORT, bortezomib; CFZ, carfilzomib; DARA, daratumumab; DEX, dexamethasone; LEN, lenalidomide; PI, proteasome inhibitor; POM, pomalidomide. In Italy, common 1L regimens included MEL ± DEX ± PRED (22%), Vd (6%), and thalidomide (THAL) + DEX (5%). Rd (40%) and Vd (8%) were the most common 2L regimens; by 3L, 56% and 49% of patients had received prior LEN- and BORT-containing regimens, respectively. Overall, use of Pd in 3L in Italy was higher than in Germany (12% vs 4%), whereas use of CFZ- (10% vs 21%) and DARA-based (9% vs 29%) regimens was lower. In 3L, use of conventional therapies, such as MEL (15% vs 3%), was higher in Italy versus Germany. Retreatment patterns in Germany and Italy showed that 60% and 82% of patients initiating 3L treatment, respectively, had prior exposure to the same agent class (IMiD, PI, monoclonal antibodies). Of 50 patients in Germany receiving BORT in 3L, 47 (94%) had prior BORT; of 135 patients receiving LEN in 3L, 47 (35%) had prior LEN. Of 40 patients in Italy receiving BORT in 3L, 31 (78%) had prior BORT; of 131 patients receiving LEN in 3L, 82 (63%) had prior LEN. Additionally, of 13 patients in Italy who received prior THAL, all were retreated with THAL in 3L. Conclusions: This study provides a perspective of RW clinical practice from 2012-2020 for comparison with the evolving treatment landscape for RRMM.