Background：

Carfilzomib, a second-generation proteasome inhibitor, demonstrates superior inhibition of the proteasome's chymotrypsin-like site compared to bortezomib [1]. It is widely used in both newly diagnosed and bortezomib-refractory multiple myeloma patients due to its higher efficacy and lower toxicity. Approved for treating refractory and relapsed multiple myeloma based on the phase III trial (CTR20160857), carfilzomib has shown significant improvements in overall survival (OS) and progression-free survival (PFS) in clinical trials [2][3]. However, studies on its real-world clinical outcomes remain limited.

Aims：

This study aims to evaluate the safety and efficacy of carfilzomib-based regimens in a clinical practice setting in China.

Method：

A retrospective study was conducted on 69 patients treated with carfilzomib-based regimens who were evaluable for treatment response at Sun Yat-sen University Cancer Center from April 2020 to June 2024. Among these patients, 20 had newly diagnosed multiple myeloma (NDMM), 32 received carfilzomib as a second-line treatment, and 17 as third-line or subsequent therapy. Carfilzomib was administered at doses of 70 mg/m² once a week or 27 mg/m² twice a week.

Results：

The median PFS was not reached for patients who received carfilzomib as first-line or third-line treatment. The median PFS was 15 months (95% CI: 15-NR) for patients treated with carfilzomib as second-line treatment. Only one patient who received carfilzomib as third or later line therapy died. The overall response rate (ORR) was 100% for first-line therapy with a complete response (CR) of 60%, 75% for second-line therapy with a CR of 25%, and 76% for third-line or later therapy with a CR of 47%. Comparisons were made between patients receiving daratumumab plus carfilzomib-based therapy versus carfilzomib-based therapy alone in each subgroup.

In NDMM patients, the ORR was 100% for carfilzomib-based treatment with a CR of 56% and 100% for daratumumab plus carfilzomib-based treatment with a CR of 75%. For second-line therapy, the ORR was 67% for carfilzomib alone with a CR of 20% and 82% for the combination with daratumumab with a CR of 29%. In third-line or later therapy, the ORR was 40% for carfilzomib alone with a CR of 20% and 92% for the combination with a CR of 58%.

Regarding prior refractory drugs, 8 patients were refractory to immunomodulatory agents (IMiDs), 5 to proteasome inhibitors (PI), 22 to both IMiDs and PI, and 6 to daratumumab-based therapy. The ORR was 75% for IMiD-refractory patients with a CR of 38%, 80% for PI-refractory patients with a CR of 40%, 77% for those refractory to both with a CR of 36%, and 83% for daratumumab-refractory patients with a CR of 33%. For patients not refractory to previous therapies, the ORR was 89% with a CR of 46%. For those with extramedullary disease (EMD), the ORR was 79% with a CR of 43%.

Based on high-risk cytogenetic abnormalities (HRA), 25 patients had no HRA, 21 had one HRA, and 8 had two or more HRA. The ORR was 76% for those without HRA with a CR of 40%, 100% for those with one HRA with a CR of 48%, and 63% for those with two or more HRA with a CR of 50%.

During treatment, some patients experienced elevated Brain Natriuretic Peptide (BNP) levels, manageable with appropriate interventions. The most common hematological toxicities of any grade were thrombocytopenia (22%), anemia (22%), and neutropenia (20%).

Conclusion：

Carfilzomib-based treatment demonstrates favorable efficacy among patients with EMD, HRA, and drug resistance. Notably, combining daratumumab with carfilzomib-based therapy shows higher efficacy than carfilzomib alone in patients with relapsed/refractory (R/R) multiple myeloma. Additionally, carfilzomib has a manageable cardiotoxicity profile, enhancing its suitability for clinical use.

References：

1. Kortuem, KM, Stewart, AK. Carfilzomib. BLOOD. 2013; 121 (6): 893-7. doi: 10.1182/blood-2012-10-459883

2. Stewart, AK, Rajkumar, SV, Dimopoulos, MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. NEW ENGL J MED. 2014; 372 (2): 142-52. doi: 10.1056/NEJMoa1411321

3. Dimopoulos, MA, Moreau, P, Palumbo, A, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. LANCET ONCOL. 2015; 17 (1): 27-38. doi: 10.1016/S1470-2045(15)00464-7

Disclosures

No relevant conflicts of interest to declare.

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2024
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