The PARP inhibitor veliparib can be safely added to bendamustine and rituximab and has preliminary evidence of activity in B-cell lymphoma Journal Article
| Authors: | Soumerai, J. D.; Zelenetz, A. D.; Moskowitz, C. H.; Palomba, M. L.; Hamlin, P. A. Jr; Noy, A.; Straus, D. J.; Moskowitz, A. J.; Younes, A.; Matasar, M. J.; Horwitz, S. M.; Portlock, C. S.; Konner, J. A.; Gounder, M. M.; Hyman, D. M.; Voss, M. H.; Fury, M. G.; Gajria, D.; Carvajal, R. D.; Ho, A. L.; Beumer, J. H.; Kiesel, B.; Zhang, Z.; Chen, A.; Little, R. F.; Jarjies, C.; Dang, T. O.; France, F.; Mishra, N.; Gerecitano, J. F. |
| Article Title: | The PARP inhibitor veliparib can be safely added to bendamustine and rituximab and has preliminary evidence of activity in B-cell lymphoma |
| Abstract: | Purpose: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase I study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas. Experimental Design: This dose-escalation study evaluated safety, pharmacokinetics, and preliminary efficacy of veliparib (20–400 mg twice a day, days 1–7 of 28-day cycle) and bendamustine (70 and 90 mg/m2 intravenously, days 1 and 2). A cohort expansion was conducted, which combined veliparib and bendamustine at the maximum tolerated dose (MTD) with rituximab (375 mg/m2, day 1) in patients with B-cell lymphomas. Thirty-four patients were treated in seven dose-escalation cohorts and seven patients in the dose-expansion cohort. Results: The MTD was veliparib 300 mg twice daily plus bendamustine 90 mg/m2. Dose-limiting toxicities (DLT) were anemia, nausea, hypertension, and hyperhidrosis. Grade ≥3 toxicities included lymphopenia (87.8%), anemia (19.5%), neutropenia (12.2%), thrombocytopenia (9.8%), leukopenia (9.8%), nausea (7.3%), and hypophosphatemia (7.3%). Apparent veliparib clearance was slightly lower than previously reported. Of 14 patients with lymphoma evaluable for response, five of seven (71%) on VB and six of seven (86%) on VBR achieved objective response. One patient with multiple myeloma achieved partial response. Conclusions: VB and VBR were generally well-tolerated. VBR had preliminary clinical activity in patients with B-cell lymphoma, which warrants further investigation in a phase II trial. This trial was registered at www.clinicaltrials.gov as NCT01326702. ©2017 AACR. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 23 |
| Issue: | 15 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2017-08-01 |
| Start Page: | 4119 |
| End Page: | 4126 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-16-3068 |
| PROVIDER: | scopus |
| PMCID: | PMC5541854 |
| PUBMED: | 28314788 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 5 September 2017 -- Source: Scopus |
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