Efficacy of carfilzomib-based regimens as induction/consolidation therapy in newly diagnosed multiple myeloma: A meta-analysis.
Authors: Aiman Wajeeha , Ali Muhammad Ashar , Usman Rana Muhammad , Tehzeeb Javaria , Solipuram Divya , Bajwa Umair Farooq , Parvez Ateeb , Tan Jia Yi , Ukrani Janta , Maroules Michael , Anwer Faiz 
Published: June 2024

e19535

Background: Carfilzomib (K) is a 2nd generation selective and irreversible proteosome inhibitor. It has shown encouraging results in newly diagnosed multiple myeloma (NDMM) patients. However, no direct comparisons were made among different regimens. This analysis aims to compare efficacy with different K-based regimens in NDMM. Methods: A literature search was done on PubMed and Embase with keywords for “Carfilzomib” and “multiple myeloma” till 1/1/2024. 25 articles (N = 3221) were included after screening 2800 articles. Data was collected for overall response rate (ORR), complete response (CR), minimal residual disease negativity (MRD-), 2-year progression free survival (PFS), and 2-year overall survival (OS). Survival data was extracted from visualization of Kaplan-Meier curve if not provided in text. R software was used for the meta-analysis. Results: In one trial (N = 72), ORR and CR were 90% and 7%, respectively in patients with K and dexamethasone (d). In one trial (N = 111), ORR, CR, PFS, and OS were 93%, 18%, 74%, and 96%, respectively with Kd and thalidomide (T). In six trials (N = 844), ORR, CR, MRD-, PFS, and OS were 92%, 43%, 38%, 78%, and 88%, respectively with Kd and lenalidomide (R). In one trial (N = 22), ORR, CR, and MRD-, were 100%, 64%, and 23%, respectively with Kd and Bendamustine (B). In three trials (N = 576), ORR, CR, MRD-, PFS, and OS were 82%, 23%, 16%, 48%, and 82%, respectively with Kd, and melphalan (M). In three trials (N = 189), ORR, CR, MRD-, PFS, and OS were 89%, 24%, 30%, 71%, and 89%, respectively with Kd and cyclophosphamide (Cy). In two trials (N = 63), ORR, CR, MRD-, PFS, and OS were 97%, 86%, 55%, 95%, and 100%, respectively with KRd and daratumumab (D). In one trial (N = 64), ORR, CR, PFS, and OS were 91%, 8%, 77%, and 95%, respectively with KCyTd. In one trial (N = 46), ORR, CR, MRD-, PFS, and OS were 96%, 70%, 65%, 80%, and 89%, respectively with KRd and elotuzumab (E). In one trial (N = 125), ORR, CR, MRD-, PFS, and OS were 94%, 70%, 79%, 70%, and 78%, respectively with KRd and isatuximab (I). In one trial (N = 526), ORR, CR, MRD-, and PFS were 90%, 18%, 17%, and 78%, respectively with KCyRd. In three trials (N = 280), ORR, CR, MRD-, PFS, and OS were 97%, 66%, 60%, 87%, and 94%, respectively with KRd and stem cell transplant (SCT). In two trials (N = 180), ORR, CR, MRD-, PFS, and OS were 91%, 55%, 43%, 70%, and 85%, respectively with KCyd-SCT. In one trial (N = 123), ORR, CR, MRD-, PFS, and OS were 98%, 86%, 80%, 87%, and 94%, respectively with KRDd-SCT. Conclusions: Among K based regimens, the highest response and 2-year-survival rates were achieved with KRDd, IKRd and were comparable to regimens with SCT. Highest MRD negativity was achieved with KRDd-SCT and IKRd. Hence, four drug regimens can be considered in NDMM to achieve high response and survival rates instead of SCT especially in patients who cannot tolerate or chose not to undergo SCT. Long-term results are needed to confirm these results.