Efficacy and Safety of Carfilzomib-Based Regimens in Multiple Myeloma: Single-Center Real-World Experience

Background:

Carfilzomib (K) is a second-generation proteasome inhibitor and has been one recommended drug for multiple myeloma (MM) patients due to its outstanding performance in clinical trials. However, there is still no report on efficacy and safety of K-based regimens in MM patients treated in real world in China.

Methods:

A retrospective analysis was conducted on MM patients treated with K-based regimen at the Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital from January 2022 to April 2024. Carfilzomib was administered on days 1, 2, 8, 9, 15 and 16 of each 28-day cycle ( 20mg/m² on days 1 and 2 during cycle 1 and 27 mg/m² thereafter). Dexamethasone was given on days 1, 2, 8, 9, 15 and 16 of each 28-day cycle via intravenous infusion ( 10 mg for patients > 75 years, 20 mg for patients ≤ 75 years). Other drugs were given according to Chinese Society of Clinical Oncology (CSCO) guidelines or International Myeloma Working Group (IMWG) guidelines or National Comprehensive Cancer Network (NCCN) guidelines. Doses of drugs and frequency of treatment were adjusted according to toxicities. Patient characteristics, treatment information, efficacy outcomes and safety were recorded and summarized. IMWG criteria was used to evaluate responses and toxicities were graded using common terminology criteria for adverse events (CTCAE 5.0). Survival analysis, including progression free survival (PFS) and overall survival (OS), was performed using the Kaplan-Meier method.

Results:

A total of 100 MM patients were recorded, and 89 of them were included in the analysis since 11 of them could not provide clear information of prior treatment. Fifty-one (57.3%) patients were male and median age was 59 years (range 38-77), 62 (69.66%) patients were older than 65 years, 26 (29.21%) had high-risk cytogenetics (del 17p, t(4;14), t(14;16), gain or amp1q), 13 (14.61%) had R-ISS stage III disease, 13 (14.61%) had extramedullary disease, 3 (3.37%) were newly diagnosed multiple myeloma (NDMM), 52 (58.43%) received at least 2 prior lines, 74 (83.15%) were exposed to bortezomib, 21 (23.60%) were refractory to bortezomib, 67 (75.28%) were exposed to lenalidomide, 62 (69.66%) were refractory to lenalidomide, 43 (48.31%) received KPd (carfilzomib, pomadomide and dexamethasone) and 18 (20.22%) received KRd (carfilzomib, lenalidomide and dexamethasone) . The overall response (ORR) was 77.53%, very good partial responses (VGPR) or better rate was 57.30% . ORR of patients received prior ≤ 1 treatment line, 2~3 treatment lines and ≥ 4 treatment lines were 96.9%, 86.7% and 61.1%, respectively. The ORR of patients received less than 3 cycles of K-based regimens was 67.9%, and reached to 100% when patients treated at least 5 cycles.With a median follow up of 10 (1-23) months, both of median PFS and OS were not reached.1 year PFS rate was 93.5%（95%CI, 87.9%-99.4%）and 1 year OS rate was 98.9%(95%CI, 96.7%-100%). Eighteen (20.22%) patients suffered cardiovascular events after carfilzomib treatment, but 10 of them already had cardiovascular abnormalities before carfilzomib regimen. Among these 10 patients, 1 had to discontinue since the heart rate persistently dropped, the other 9 patients did not get worse. The most common grade 3+ hematological adverse events were anemia (25.84%), lymphocytopenia (30.34%), neutropenia (17.97%), and thrombocytopenia (15.73%). None of patients required permanent discontinuation related to hematological adverse events.

Conclusions:

K-based regimens produce high ORR not only in NDMM patients, but also in relapsed/refractory MM patients with durable responses. The adverse reactions were tolerable, but history of cardiovascular abnormalities should be paid attention. Our data highlights the effectiveness of K-based regimens in MM patients in real world.

No relevant conflicts of interest to declare.