Efficacy and safety of carfilzomib in relapsed and/or refractory multiple myeloma: systematic review and meta-analysis of 14 trials
| Autor: | Samip Master, Yu Wang, Rohit Bishnoi, Fei Zou, Jan S. Moreb, Chintan Shah, Harini Bejjanki |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty efficacy law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Randomized controlled trial law Internal medicine Medicine Cumulative incidence Multiple myeloma Hematology carfilzomib response business.industry Odds ratio medicine.disease Carfilzomib Clinical trial multiple myeloma 030104 developmental biology chemistry 030220 oncology & carcinogenesis Meta-analysis kyprolis business Meta-Analysis |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Chintan Shah 1 , Rohit Bishnoi 1 , Yu Wang 2 , Fei Zou 2 , Harini Bejjanki 1 , Samip Master 3 and Jan S. Moreb 4 1 Division of Hospital Medicine, University of Florida, Gainesville, Florida, USA 2 Department of Biostatistics University of Florida, Gainesville, Florida, USA 3 Division of Hematology/Oncology, Louisiana State University, Shreveport, Louisiana, USA 4 Division of Hematology/Oncology, University of Florida, Gainesville, Florida, USA Correspondence to: Chintan Shah, email: cps.chintan@gmail.com ; Chintan.shah@medicine.ufl.edu Keywords: carfilzomib; kyprolis; multiple myeloma; response; efficacy Received: January 03, 2018 Accepted: April 06, 2018 Published: May 04, 2018 ABSTRACT Objective: Carfilzomib (Carf) is a second-generation proteasome inhibitor approved for patients with relapsed and/or refractory multiple myeloma (RRMM) who failed ≥ 1 prior lines of therapy. We performed a systematic review of Carf literature with meta-analysis to determine the efficacy and safety in RRMM patients. Methods: Based on literature search, we included a total of 14 eligible phase I/II, phase II and phase III Carf based clinical trials. The cumulative incidence and odds ratios (OR) were calculated with random effect model, using ‘’R’’ software with metaphor package. Results: 2906 evaluable RRMM patients from published clinical trials included. The pooled overall response rate (ORR) was 45% (95% CI: 29–62). The pooled clinical benefit rate (CBR) was 56% (95% CI: 41–71). OR from 3 randomized clinical trials showed that Carf significantly improved ORR and CBR compared to control groups (OR 2.4, P 20/27 mg/m 2 ) compared to standard dose (ORR 65% vs. 35%, P = 0.03). Compared to control group, the OR of developing cardiotoxicity ( P = 0.002) and hypertension ( P < 0.0001) were significantly higher with Carf, while no difference in peripheral neuropathy ( P = 0.28). Conclusions: Carf produces significantly better responses with acceptable safety profile in RRMM patients. Combination regimens and higher dose Carf offers better response with no significant extra toxicity. Its efficacy is regardless of cytogenetics or disease stage. Incidences of cardiotoxicity and hypertension seem higher with Carf. |
| Databáze: | OpenAIRE |
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