Polatuzumab vedotin with infusional chemotherapy for untreated aggressive B-cell non-Hodgkin lymphomas.

Abstract

The POLARIX trial demonstrated the superiority of polatuzumab vedotin (Pola) over vincristine in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) regimen for large B-cell lymphomas, but it is unknown whether Pola can be safely incorporated into intensified regimens (eg, dose-adjusted [DA]-EPOCH-R [etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab]) typically used for the highest risk histologies. This was a single-center, open-label, prospective clinical trial of 6 cycles of Pola-DA-EPCH-R (vincristine omitted) in aggressive large B-cell lymphomas. The primary end point was to estimate the safety of Pola-DA-EPCH-R as measured by the rate of dose-limiting toxicities (DLTs) in the first 2 cycles with prespecified suspension rules. Secondary and exploratory end points included efficacy and correlation with circulating tumor DNA (ctDNA) levels. We enrolled 18 patients on study, and with only 3 DLTs observed, the study met its primary end point for safety. There were 5 serious adverse events, including grade 3 febrile neutropenia (3, 17%), grade 3 colonic perforation in the setting of diverticulitis, and grade 5 sepsis/typhlitis. Among 17 evaluable patients, the best overall response rate was 100%, and the complete response rate was 76%. With a median follow-up of 12.9 months, 12-month event-free survival was 72%, and 12-month overall survival was 94%. No patient with undetectable ctDNA at the end of treatment has relapsed to date. Using Pola to replace vincristine in the DA-EPOCH-R regimen met its primary safety end point. These data support the further evaluation and use of this approach in histologies where the potential benefit of both an intensified regimen and Pola may be desired. This trial was registered at www.clinicaltrials.gov as #NCT04231877.

• Authors: Ryan C Lynch, Christina Poh, Chaitra S Ujjani, Edus H Warren, Stephen D Smith, Mazyar Shadman, Karolyn Morris, Sydney Lee, Heather Rasmussen, Susan Ottemiller, Megan Shelby, Sarith Keo, Kaitlin Verni, David M Kurtz, Ash A Alizadeh, Jacob J Chabon, Gregory J Hogan, Andre Schulz, Ted Gooley, Jenna M Voutsinas, Ajay K Gopal
• Journal: Blood advances (Blood Adv) Vol. 7 Issue 11 Pg. 2449-2458 (06 13 2023) ISSN: 2473-9537 [Electronic] United States
• PMID: 36521030 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• Cyclophosphamide
• Doxorubicin
• Etoposide
• polatuzumab vedotin
• Prednisone
• Rituximab
• Vincristine

Topics

• Humans
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Cyclophosphamide (adverse effects)
• Doxorubicin (adverse effects)
• Etoposide (adverse effects)
• Lymphoma, Large B-Cell, Diffuse (drug therapy)
• Prednisone (adverse effects)
• Prospective Studies
• Rituximab (adverse effects)
• Vincristine (adverse effects)