Carfilzomib, Pomalidomide, Dexamethasone with and without Daratumumab in Relapsed/Refractory Multiple Myeloma: A Multi-Center, Prospective Real World Study in China

Objective

To evaluate the efficacy and safety of carfilzomib, pomalidomide and dexamethasone with or without daratumumab(KPd±Dara) in relapsed/refractory multiple myeloma (RRMM) in the real world practice.

Methods

This was a multicenter, prospective, real-world cohort study in patients with relapsed/refractory MM in six hospitals from north China since 2022. Patients aged 18 years or older who had received one or more prior lines of therapy were eligible and treated with KPd ±Dara till disease progression. Clinical data, including baseline characteristics, cytogenetic abnormalities, extramedullary and adverse effects were collected. This study has been approved by the Ethics Committee of Peking Union Medical College Hospital (No. I-23PJ1615).

Carfilzomib was administrated with 20 mg/m² d1-2, 70 mg/m² d 8, 15, oral pomalidomide 4mg on days 1-21, and dexamethasone 40mg weekly in 28-days cycles. Dara was given as routine doses. The primary endpoints were overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS) and overall survival (OS). Statistical methods mainly adopt χ ²-test, t-test, Kaplan Meier, and COX regression analysis.

Results

A total of 78 patients were enrolled in the cohort, 51 for KPd and 27 for Dara-KPd.

Median age was 62 years(range 47-79, 28%＞65 years) for KPd and 63（range 44-84,) for Dara-KPd. Baseline characteristics were matched between two groups, including paraprotein type, International Staging System(ISS), R-ISS, cytogenetic abnormalities and autologous stem-cell transplantation (ASCT) (P＞0.05). 20.4% of patients were diagnosed with primary or secondary plasma cell leukemia (PCL), while 33.3% of patients developed extramedullary disease. High-risk cytogenetics as defined by the mSMART 3.0, including 1q21, t(4;14),t(14;16) and del(17) , were present in 34/43(79.1%) of the total cohort, with 22/27(81.5%) of the KPd and 12/16(75.0%) of the Dara-KPD. During front-line treatment, the majority of patients were exposed to lenalidomide (85.2%) or bortezomib (98.1%). The median time from diagnosis was 29.5 months, 27m for KPd and 37m for Dara-KPd, respectively. The median prior lines of therapy was 2 for KPd (37.1% with 3 or more) and 2 for Dara-KPd (13% with 3 or more). The median follow-up time was 11[5,14] months. The ORR was 39/54 (72.2%), 68.8% for the triplet and 77.3% for the quadruplet. 75% of the extramedullary lesions responded. Kaplan-Meier survival analysis suggested that median PFS and OS have not been reached(NR) in the whole cohort, similar in the two groups(PFS: NR[5-NR ] vs 8[5-11]months, P=0.142; OS：NR[17-NR] vs NR[17-NR], P=0.951). Hematologic adverse events (AEs) were common in both groups, most with grade 1 or 2. Cardiovascular toxicities were of low grades: 8.2% with hypertension, 14% with palpitations.

Conclusion

In the era of VRd as front-line regimens in MM, second generation PIs combined with IMiDs and/or anti-CD38 antibody were still preferred. Our study demonstrated the efficacy and safety of KPd±Dara among Chinese population in real-world practice. For RRMM patients exposed to lenalidomide and/or bortezomib presenting high-risk features, KPd±Dara could be a safe and effective option.

No relevant conflicts of interest to declare.