Clinical studies of PARP inhibitors in hematologic malignancies
| PARP inhibitor . | Phase . | Study . | Treatment . | Malignancy . | Number of patients . | ClinicalTrials.gov identifier . | Findings . |
|---|---|---|---|---|---|---|---|
| Talazoparib | 1 | Gopal et al, 2021112 | Monotherapy | Refractory AML, MDS, CLL, and MCL | 33 | NCT01399840 | Well tolerated. The MTD of 2.0 mg per day in the AML/MDS cohort and 0.9 mg per day in the CLL/MCL cohort was comparable to that for solid tumors. Stable disease was observed in 18 patients. |
| Olaparib | 1 | Pratt et al 2018113 | Monotherapy | Refractory CLL, T-PLL, and MCL | 15 | ISRCTN34386131 | Well tolerated. Most common dose-limiting toxicities were hematologic. Patients harboring defects in the ATM pathway displayed a trend toward more durable response. |
| Veliparib | 1 | Pratz et al, 2017114 | Combination with topotecan and carboplatin | Refractory AML, MPN, and CMML | 99 | NCT00588991 | Acceptable safety and tolerability. Objective response was observed in 33 patients and complete response in 25 of 99 patients. Leukemic cells from responders displayed increased H2AX phosphorylation. |
| Veliparib | 1 | Gojo et al, 2017115 | Combination with temozolomide | High-risk AML | 48 | NCT01139970 | No dose-limiting toxicity. Complete response was observed in 8 of 48 patients. Clinical response correlated with MGMT promoter hypermethylation and treatment-induced H2AX phosphorylation. |
| Talazoparib | 1 | Baer et al, 2022116 | Combination with decitabine | Refractory AML | 22 | NCT02878785 | Well tolerated. Complete remission was observed in 2 patients and hematologic improvement in 3 patients. Responding patients displayed DNA demethylation, increased PARP-trapping in chromatin, increased γH2AX foci, and decreased HRR activity. |
| PARP inhibitor . | Phase . | Study . | Treatment . | Malignancy . | Number of patients . | ClinicalTrials.gov identifier . | Findings . |
|---|---|---|---|---|---|---|---|
| Talazoparib | 1 | Gopal et al, 2021112 | Monotherapy | Refractory AML, MDS, CLL, and MCL | 33 | NCT01399840 | Well tolerated. The MTD of 2.0 mg per day in the AML/MDS cohort and 0.9 mg per day in the CLL/MCL cohort was comparable to that for solid tumors. Stable disease was observed in 18 patients. |
| Olaparib | 1 | Pratt et al 2018113 | Monotherapy | Refractory CLL, T-PLL, and MCL | 15 | ISRCTN34386131 | Well tolerated. Most common dose-limiting toxicities were hematologic. Patients harboring defects in the ATM pathway displayed a trend toward more durable response. |
| Veliparib | 1 | Pratz et al, 2017114 | Combination with topotecan and carboplatin | Refractory AML, MPN, and CMML | 99 | NCT00588991 | Acceptable safety and tolerability. Objective response was observed in 33 patients and complete response in 25 of 99 patients. Leukemic cells from responders displayed increased H2AX phosphorylation. |
| Veliparib | 1 | Gojo et al, 2017115 | Combination with temozolomide | High-risk AML | 48 | NCT01139970 | No dose-limiting toxicity. Complete response was observed in 8 of 48 patients. Clinical response correlated with MGMT promoter hypermethylation and treatment-induced H2AX phosphorylation. |
| Talazoparib | 1 | Baer et al, 2022116 | Combination with decitabine | Refractory AML | 22 | NCT02878785 | Well tolerated. Complete remission was observed in 2 patients and hematologic improvement in 3 patients. Responding patients displayed DNA demethylation, increased PARP-trapping in chromatin, increased γH2AX foci, and decreased HRR activity. |
CMML, chronic myelomonocytic leukemia; MCL, mantle cell lymphoma; MPN, myeloproliferative neoplasms; MTD, maximum tolerable drug dose; T-PLL, T-cell prolymphocytic leukemia.