TY - JOUR
T1 - Incidence of myelodysplastic syndrome and acute myeloid leukemia in patients receiving poly-ADP ribose polymerase inhibitors for the treatment of solid tumors
T2 - A meta-analysis of randomized trials
AU - Nitecki, Roni
AU - Melamed, Alexander
AU - Gockley, Allison A.
AU - Floyd, Jessica
AU - Krause, Kate J.
AU - Coleman, Robert
AU - Matulonis, Ursula A.
AU - Giordano, Sharon H.
AU - Lu, Karen H.
AU - Rauh-Hain, J. Alejandro
N1 - Funding Information:
This work was supported by grants from The National Institutes of Health, National Cancer Institute [JARH: K08 CA234333; RN, SG, KL, and JARH: P30 CA016672; KL: 5T32 CA101642], and National Center for Advancing Translational Sciences [AM: KL2TR001874]. Editorial support was provided by Ann M. Sutton in Scientific Publications, Research Medical Library, MD Anderson.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/6
Y1 - 2021/6
N2 - Background: Clinical trials demonstrated that PARPi (poly [adenosine diphosphate–ribose]-ADP polymerase inhibitor) therapy is effective in solid tumors. However, long term effects such as therapy-related myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) are poorly described. We sought to quantify whether PARPi therapy is associated with the development of MDS/AML. Methods: Medline, Embase, and Cochrane databases were searched (inception to January 6, 2020) and phase 2 and 3 clinical trials that randomized patients with solid tumors to a PARPi or control therapy were included. The PRISMA guidelines were used to extract data independently by multiple authors. We extracted person-time and number of cases of MDS/AML in the PARPi and control arms of each study and pooled results with a random-effects Poisson regression model. The pooled incidence rate ratio (IRR) for MDS/AML among patients randomized to PARPi therapy was compared to those randomized to a control. Results: We identified 14 studies that included 5739 patients. Accounting for intra-study clustering, the risk of MDS/AML was similar in patients who were randomly assigned to receive PARPi compared to controls (IRR 1.32, 95% confidence interval [CI] 0.78–2.26). In the front-line setting, PARPi therapy was associated with developing MDS/AML (IRR 5.43, 95% CI 1.51–19.60). Among patients treated for recurrence, however, the risk of MDS/AML appeared to be similar among patients randomized to PARPi or control treatment. Among studies that included only patients with a BRCA mutation, the risk of MDS/AML was similar in both treatment groups (IRR 0.83, 95% CI 0.45–1.53), but PARPi therapy was associated with MDS/AML in studies with an unrestricted population (IRR 2.43, 95% CI 1.17–5.06). Conclusion: The pooled overall effect was not statistically significant. However, treatment with PARPi was associated with a statistically significant increase in the incidence of MDS/AML among patients receiving front-line cancer therapy and those with limited prior exposure to chemotherapy.
AB - Background: Clinical trials demonstrated that PARPi (poly [adenosine diphosphate–ribose]-ADP polymerase inhibitor) therapy is effective in solid tumors. However, long term effects such as therapy-related myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) are poorly described. We sought to quantify whether PARPi therapy is associated with the development of MDS/AML. Methods: Medline, Embase, and Cochrane databases were searched (inception to January 6, 2020) and phase 2 and 3 clinical trials that randomized patients with solid tumors to a PARPi or control therapy were included. The PRISMA guidelines were used to extract data independently by multiple authors. We extracted person-time and number of cases of MDS/AML in the PARPi and control arms of each study and pooled results with a random-effects Poisson regression model. The pooled incidence rate ratio (IRR) for MDS/AML among patients randomized to PARPi therapy was compared to those randomized to a control. Results: We identified 14 studies that included 5739 patients. Accounting for intra-study clustering, the risk of MDS/AML was similar in patients who were randomly assigned to receive PARPi compared to controls (IRR 1.32, 95% confidence interval [CI] 0.78–2.26). In the front-line setting, PARPi therapy was associated with developing MDS/AML (IRR 5.43, 95% CI 1.51–19.60). Among patients treated for recurrence, however, the risk of MDS/AML appeared to be similar among patients randomized to PARPi or control treatment. Among studies that included only patients with a BRCA mutation, the risk of MDS/AML was similar in both treatment groups (IRR 0.83, 95% CI 0.45–1.53), but PARPi therapy was associated with MDS/AML in studies with an unrestricted population (IRR 2.43, 95% CI 1.17–5.06). Conclusion: The pooled overall effect was not statistically significant. However, treatment with PARPi was associated with a statistically significant increase in the incidence of MDS/AML among patients receiving front-line cancer therapy and those with limited prior exposure to chemotherapy.
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U2 - 10.1016/j.ygyno.2021.03.011
DO - 10.1016/j.ygyno.2021.03.011
M3 - Article
C2 - 33736856
AN - SCOPUS:85102645021
SN - 0090-8258
VL - 161
SP - 653
EP - 659
JO - Gynecologic oncology
JF - Gynecologic oncology
IS - 3
ER -