Real-World Use of Carfilzomib for the Treatment of Relapsed/Refractory Multiple Myeloma in Germany: Once-Weekly and Twice-Weekly Administration Schedules
Authors: Trautmann-Grill Karolin , Kossack Nils , El Hadad Laila , Najafi Bahar , Kaehm Katharina , Boehm Doris , Papkalla Armin , Pignot Marc , Samuel Amir , Katz Jessica , Dhamane Amol D. 
Published: December 2024

Introduction: The doublet therapy of carfilzomib (CFZ) in combination with dexamethasone is commonly used to treat multiple myeloma (MM) in clinical practice and is used as a comparator in several randomized clinical trials. It is approved for once-weekly (70 mg/m2) and twice-weekly (56 mg/m2) administration in the United States (US), although only the twice-weekly dose is approved in the European Union. There is limited consensus on the efficacy and safety of the CFZ dosing schedules (A.R.R.O.W. trial; Moreau P, et al. Lancet Oncol 2018;19:953-964); however, clinical practice indicates that treatment burden, patient (pt) preference as well as the limited infusion capacities of office-based medical practices may influence this choice.

Objective: To describe and compare characteristics of pts with MM in Germany who were administered CFZ on a once-weekly, twice-weekly, or mixed frequency (phases of once- and twice-weekly) schedule.

Methods: A retrospective cohort study was conducted in pts ≥ 18 years of age diagnosed with MM and treated with CFZ based on anonymized, representative German healthcare claims data. The dataset comprised over 9 million insured individuals from various German sickness funds from 2014 to 2022. The index date was defined as the date of the first prescription for CFZ between June 26, 2016, and June 30, 2022. Pts had a minimum baseline observation period of 12 months before the index date and a minimum follow-up period of 6 months after the index date (or until death). Pts treated in hospitals exclusively and those receiving CFZ-containing triplet regimens at the index date or within 30 days after the index date were excluded. The pts were categorized into 3 cohorts based on CFZ administration frequency: once weekly, twice weekly, or those who could not be assigned to either dosing cohort (mixed frequency). Trend analysis assessed changes in CFZ use with respect to administration frequency, defined as the frequency of dispensed CFZ vials per week. Baseline pt demographics and clinical characteristics were assessed during the 12-month baseline period. Univariate statistical comparisons of baseline pt characteristics were performed among the cohorts (pairwise between once weekly and twice weekly and between twice weekly and mixed frequency) to identify potential factors associated with the choice of CFZ administration frequency.

Results: Of 864 pts initiating CFZ treatment between 2016 and 2022, a total of 395 pts remained after applying the inclusion and exclusion criteria. Of these, 119 (30.1%) pts followed a once-weekly regimen, 128 (32.4%) followed a twice-weekly regimen, and 148 (37.5%) received a mixed-frequency regimen. Of the 395 pts, 245 (62.0%) were male, and the mean age was 70.4 (range, 43-90) years. Generally, there were no statistically significant differences in the pt characteristics between the cohorts based on administration frequency. Pts in the once-weekly cohort were slightly older than those in the twice-weekly or mixed-frequency cohort (71.6 vs 69.9 years; P = 0.417). The once-weekly cohort compared with the twice-weekly cohort showed a relatively comparable comorbidity burden as measured by the mean Charlson Comorbidity Index (5.7 vs 5.2; P = 0.397); a higher proportion of pts had diagnoses of renal disease (47.9% vs 37.5%; P = 0.128), neutropenia (16.0% vs 8.6%; P = 0.115), thrombocytopenia (20.2% vs 13.3%; P = 0.200), bone pain (8.4% vs 4.7%; P = 0.354), coronary artery disease (26.1% vs 21.1%; P = 0.535), and hypertension (72.3% vs 68.8%; P = 0.641), respectively.

Trend analysis showed that the proportion of pts with once-weekly administration consistently increased from 2016 to 2022 (2016: 25.8%; 2017: 21.7%; 2018: 27.6%; 2019: 24.0%; 2020: 40.0%; 2021: 40.9%; 2022: 47.8%), with a statistically significant linear trend (R2 = 0.79). Conversely, the proportion of pts with twice-weekly administration generally decreased from 36.4% in 2016 to 21.7% in 2022, while the proportion of pts with mixed-frequency administration decreased from 37.9% in 2016 to 30.4% in 2022.

Conclusion: This real-world study of pts with MM treated with CFZ in Germany demonstrates that a considerable proportion of pts received CFZ as a once-weekly administration. This dosing schedule became increasingly common between 2018 (the year of once-weekly dose approval in the US) and 2022, whereas the twice-weekly administration schedule decreased in the same period.