TY - JOUR
T1 - Cardiotoxicity associated with carfilzomib
T2 - systematic review and meta-analysis
AU - Shah, Chintan
AU - Bishnoi, Rohit
AU - Jain, Ankur
AU - Bejjanki, Harini
AU - Xiong, Sican
AU - Wang, Yu
AU - Zou, Fei
AU - Moreb, Jan S.
N1 - Publisher Copyright:
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2018/11/2
Y1 - 2018/11/2
N2 - Carfilzomib is a second-generation proteasome inhibitor (PI) that is approved for patients with relapsed or refractory multiple myeloma (RRMM) who failed ≥1 prior lines of therapy. We performed a systematic review of carfilzomib literature with meta-analysis to determine cumulative incidence of cardiotoxicity. After the literature search, we included a total of 29 eligible phase I/II, phase II and phase III clinical trials which used carfilzomib. The cumulative incidence and overall odds ratios (OR) were calculated with random effect model, using ‘R’ software with metaphor package. A total of 4164 patients with various malignancies were included. The overall estimated cumulative incidence of cardiotoxicity was 8.68% and 4.92%, respectively, for all-grade and high-grade (≥ grade 3) toxicity, which seems higher than other PIs. Compared to control group, the odds of developing cardiotoxicity due to carfilzomib was significantly higher with OR of 2.03 (95% CI: 1.19–3.46, p =.010) and 2.04 (95% CI: 1.31–3.17, p =.002) for all-grades and high grades, respectively. Concomitant immunomodulatory agents seem to increase the risk of cardiotoxicity (high-grade cardiotoxicity 6.45% and 4.34% with and without concomitant immunomodulatory agents, respectively (p =.033)). There was no variation in the incidence of cardiotoxicity among newly diagnosed versus RRMM (p =.38), and high versus standard dose carfilzomib (p =.86).
AB - Carfilzomib is a second-generation proteasome inhibitor (PI) that is approved for patients with relapsed or refractory multiple myeloma (RRMM) who failed ≥1 prior lines of therapy. We performed a systematic review of carfilzomib literature with meta-analysis to determine cumulative incidence of cardiotoxicity. After the literature search, we included a total of 29 eligible phase I/II, phase II and phase III clinical trials which used carfilzomib. The cumulative incidence and overall odds ratios (OR) were calculated with random effect model, using ‘R’ software with metaphor package. A total of 4164 patients with various malignancies were included. The overall estimated cumulative incidence of cardiotoxicity was 8.68% and 4.92%, respectively, for all-grade and high-grade (≥ grade 3) toxicity, which seems higher than other PIs. Compared to control group, the odds of developing cardiotoxicity due to carfilzomib was significantly higher with OR of 2.03 (95% CI: 1.19–3.46, p =.010) and 2.04 (95% CI: 1.31–3.17, p =.002) for all-grades and high grades, respectively. Concomitant immunomodulatory agents seem to increase the risk of cardiotoxicity (high-grade cardiotoxicity 6.45% and 4.34% with and without concomitant immunomodulatory agents, respectively (p =.033)). There was no variation in the incidence of cardiotoxicity among newly diagnosed versus RRMM (p =.38), and high versus standard dose carfilzomib (p =.86).
KW - cardiotoxicity
KW - Carfilzomib
KW - kyprolis
KW - multiple myeloma
KW - toxicity
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U2 - 10.1080/10428194.2018.1437269
DO - 10.1080/10428194.2018.1437269
M3 - Review article
C2 - 29465266
AN - SCOPUS:85042218253
SN - 1042-8194
VL - 59
SP - 2557
EP - 2569
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 11
ER -