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
Altmetric
Citation Impact
MSK Authors
  1. Zhigang Zhang
    275 Zhang
  2. Carol Portlock
    198 Portlock
  3. Craig Moskowitz
    388 Moskowitz
  4. Ariela Noy
    226 Noy
  5. Maria Lia Palomba
    166 Palomba
  6. Richard D Carvajal
    145 Carvajal
  7. Jason Konner
    105 Konner
  8. Steven M Horwitz
    412 Horwitz
  9. Martin Henner Voss
    169 Voss
  10. Devika Gajria
    27 Gajria
  11. Matthew G Fury
    101 Fury
  12. Andrew D Zelenetz
    600 Zelenetz
  13. Mrinal M Gounder
    110 Gounder
  14. David Hyman
    302 Hyman
  15. Alison Moskowitz
    179 Moskowitz
  16. Paul Hamlin
    186 Hamlin
  17. Matthew J Matasar
    151 Matasar
  18. Alan Loh Ho
    121 Ho
  19. David J Straus
    247 Straus
  20. Anas Younes
    248 Younes
  21. Thu-Oanh Thi Dang
    11 Dang
  22. Fallon Olga France
    4 France
  23. Nishant   Mishra
    2 Mishra