(PA-473) Carfilzomib Use and Therapeutic Sequences in Patients with Relapsed/refractory Multiple Myeloma in France: An Analysis from a Large-scale Epidemiology of Multiple Myeloma (EmmY) Cohort

Introduction: In the context of the rapidly evolving multiple myeloma (MM) treatment landscape, we aimed to explore carfilzomib (K) use and the therapeutic sequences in a French real-world cohort of K-treated patients (pts).

Methods: In 73 MM care centres, pts initiating K in second line or later (2L+) between 2017 and 2023 and followed for ≥3 months were included. This analysis is purely descriptive and focuses on K-based regimens used in ≥10% of pts.

Results: Overall, 1261 pts initiated K therapy in 2L (24.4%), 3L (25.2%), and 4L+ (50.4%). The most frequently used K-based regimens were K with dexamethasone (dex) alone (Kd; 32.5%), with pomalidomide (KPd [off-label use]; 15.9%), with lenalidomide (len) (KRd; 14.2%), with daratumumab (D-Kd; 13.9%), and with cyclophosphamide (KCd [off-label use]; 7.4%). Since 2018, Kd and KRd use declined in favor of D-Kd and KPd, and K once-weekly dosing increased over time with a majority of use since 2022.

D-Kd (N=175) was largely used in 2L (51%), 18% of pts were anti-CD38 refractory at D-Kd initiation. The main prior treatment was bortezomib (V) with len and dex (VRd; 37%). Where available (n=76), treatments used after D-Kd included CPd (20% [n=15]), teclistamab (17% [n=13]) and isatixumab (Isa) with P and dex (8% [n=6]).

KRd (N=179) was mainly used in 2L (39%) and 3L (20%). Among prior treatments, V-based triplets, mainly DVd (19% [n=34]) and thalidomide (T) with Vd (VTd: 17% [n=31]) were mostly used. After KRd, where available (n=115), anti-CD38-Pd (35% [n=40]) was the most used regimen.

KPd (N=201) was primarily used in 3L (47%) and 4L (22%) and most pts were refractory to len (91%) and to an anti-CD38 (76%). Since 2020, most KPd pts (90%) had been exposed to an anti-CD38 in a prior line of therapy, mainly DRd (35% [n=71]) and DVd (22% [n=44]). Where available (n=116), the main treatment used after KPd was teclistamab (16% [n=19]), especially since 2022.

Kd (N=410) was mostly (66%) used in 3L to 5L. Among prior treatments DRd (13% [n=53]) and DVd (12% [n=48]) were the most used. After Kd, where available (n=253), bendamustine (12% [n=31]), IsaPd (9% [n=24]) and teclistamab (8% [n=21]) were the most used regimens.

Overall response rates (ORR) were high for D-Kd (84.5% in 2L), KRd (80.6% in 2L), and KPd (77.8% in 3L and 77.9% in 4L+); with long median overall survival (mOS): D-Kd and KRd, not reached in 2L; KPd, 16.7 months in 3L and 25.6 months in 4L+.

Since 2022, the use of the new triplet Isa-Kd was very low (1.3% [n=16]) and quadruplets (D-KPd, D-KRd, Isa-KPd) were used in 3.6% (n=46) of pts, mainly in 2L 64% [n=30]). 

Conclusions: Since 2018, use of KRd declined in favor of D-Kd (2L) and KPd (3L/4L), and K once-weekly is mainly used since 2022. After D-Kd, P-based regimens were preferably considered. In 3L and 4L, KPd was the most commonly used K-based regimen to treat patients largely refractory to anti-CD38 and len. K triplets resulted in long survivals. Kd was used in one third of patients, as an option for multi-refractory patients in 3L+.