Real-world efficacy and safety of carfilzomib-based combination regimens in patients with multiple myeloma Free

Background

Multiple myeloma (MM), a heterogeneous malignancy originating from plasma cells in bone marrow, represents roughly 1% of total tumors and 10% of all hematopoietic tumors. The treatment of multiple myeloma has advanced rapidly in recent years, and regimens based on carfilzomib have shown significant improvement in survival for MM, but their real-world efficacy and safety profiles require further exploration. Here we evaluated the efficacy and safety of carfilzomib-based combination therapy in patients with MM. This was a retrospective, multicenter observational study.

Aims

To evaluate the real-world efficacy and safety of carfilzomib-based combination therapies in patients with MM.

Methods

We retrospectively analyzed clinical data from MM patients treated with carfilzomib-based regimens between August 2022 and June 2025 at two centers in China.

Results

A total of 103 patients were included. The median age was 62 years (range: 41–79) and 51.5% were male. Among 86 patients with available International Staging System (ISS) staging data, 48 (55.8%) were classified as stage III. Of the 70 patients with available cytogenetic data (locally assessed via fluorescence in situ hybridization), high-risk cytogenetic profile was defined as the presence of t (4;14), t (14;16), t (14;20), or del(17p). 14 (20.0%) patients had high cytogenetic risk, and 5 (7.1%) patients exhibited “double hit”. Only 3 patients were newly diagnosed MM, among the remaining 100 patients, 99 (99.0%) had prior exposure to bortezomib, 41.0% had received prior anti-CD38 monoclonal antibody (mAb), and 10 patients had undergone prior autologous stem cell transplantation (ASCT). The median number of prior treatment lines was 3 (range: 1-7). 16 (15.5%) patients received carfilzomib and dexamethasone (Kd) based therapy with or without anti-CD38 mAb, 46 (44.7%) received Kd combined with an immunomodulatory agent (IMiD) with or without anti-CD38 mAb, 33 (32.0%) received Kd combined with chemotherapy with or without anti-CD38 mAb, and 8 (7.8%) received Kd combined with other regimens. A total of 39 patients received anti-CD38 mAb. Patients received a median of 5 cycles (range: 1-7). Efficacy was assessed in 93 patients with an overall response rate ORR of 61.3%. Complete response (CR) was achieved in 16.1%, very good partial response (VGPR) in 14.0%, partial response (PR) in 31.2%, stable disease (SD) in 2.2%, and progressive disease (PD) in 36.6%. The median time to response was 4.5 months (range: 1-8 months). With a median follow-up of 9 months (range: 1–27), the median progression-free survival (PFS) was 13.6 months, and the median overall survival (OS) was 24.8 months. Elderly patients (≥65 years) demonstrated lower response rates, with an ORR of 49%.

In terms of adverse reactions, we paid more attention to the occurrence of cardiovascular adverse events (CVAEs). Prior to carfilzomib treatment, 32 patients (31.1%) had a history of hypertension, 2 (1.9%) had a history of heart failure, and 10 (9.7%) had a history of arrhythmia. During carfilzomib-based combination therapy, a total of 15 patients (14.6%) developed CVAEs, including heart failure, palpitations, arrhythmia, elevated troponin I (TnI) levels, and pericardial effusion. Among these, two patients experienced grade ≥3 CVAEs, one developed atrial fibrillation, which improved following amiodarone administration, and the other experienced heart failure, which was alleviated with diuretic and coronary vasodilator therapy. Hematologic toxicities were the most frequently observed adverse events, including anemia (48.0%), leukopenia (34.3%), and thrombocytopenia (24.5%). The most common non-hematologic treatment-emergent adverse events (TEAEs) were infections (30.1%). A total of 31 patients (20.1%) experienced hematologic toxicities of grade ≥3. Two patients developed grade 3–4 renal toxicity, manifesting as acute kidney failure. Additionally, complications such as pulmonary embolism, oral ulcers, allergic dermatitis, ankle joint swelling, and headache were each observed in one patient, and two patients experienced diarrhea.

Conclusion

Carfilzomib-based combination regimens demonstrated encouraging efficacy and manageable safety profiles in real-world MM patients. These results support further prospective evaluation to optimize clinical application.