Anti-CD25 radioimmunotherapy with BEAM autologous hematopoietic cell transplantation conditioning in Hodgkin lymphoma.

Abstract

High-risk relapsed or refractory (R/R) classical Hodgkin lymphoma (HL) is associated with poor outcomes after conventional salvage therapy and autologous hematopoietic cell transplantation (AHCT). Post-AHCT consolidation with brentuximab vedotin (BV) improves progression-free survival (PFS), but with increasing use of BV early in the treatment course, the utility of consolidation is unclear. CD25 is often expressed on Reed-Sternberg cells and in the tumor microenvironment in HL, and we hypothesized that the addition of 90Y-antiCD25 (aTac) to carmustine, etoposide, cytarabine, melphalan (BEAM) AHCT would be safe and result in a transplantation platform that is agnostic to prior HL-directed therapy. Twenty-five patients with high-risk R/R HL were enrolled in this phase 1 dose-escalation trial of aTac-BEAM. Following an imaging dose of 111In-antiCD25, 2 patients had altered biodistribution, and a third developed an unrelated catheter-associated bacteremia; therefore, 22 patients ultimately received therapeutic 90Y-aTac-BEAM AHCT. No dose-limiting toxicities were observed, and 0.6 mCi/kg was deemed the recommended phase 2 dose, the dose at which the heart wall would not receive >2500 cGy. Toxicities and time to engraftment were similar to those observed with standard AHCT, though 95% of patients developed stomatitis (all grade 1-2 per Bearman toxicity scale). Seven relapses (32%) were observed, most commonly in patients with ≥3 risk factors. The estimated 5-year PFS and overall survival probabilities among 22 evaluable patients were 68% and 95%, respectively, and non-relapse mortality was 0%. aTac-BEAM AHCT was tolerable in patients with high-risk R/R HL, and we are further evaluating the efficacy of this approach in a phase 2 trial. This trial was registered at www.clinicaltrials.gov as #NCT01476839.

• Authors: Alex F Herrera, Joycelynne Palmer, Vikram Adhikarla, Dave Yamauchi, Erasmus K Poku, James Bading, Paul Yazaki, Savita Dandapani, Matthew Mei, Robert Chen, Thai Cao, Nicole Karras, Pamela McTague, Auayporn Nademanee, Leslie Popplewell, Firoozeh Sahebi, John E Shively, Jennifer Simpson, D Lynne Smith, Joo Song, Ricardo Spielberger, Ni-Chun Tsai, Sandra H Thomas, Stephen J Forman, David Colcher, Anna M Wu, Jeffrey Wong, Eileen Smith
• Journal: Blood advances (Blood Adv) Vol. 5 Issue 23 Pg. 5300-5311 (12 14 2021) ISSN: 2473-9537 [Electronic] United States
• PMID: 34638132 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 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

• Yttrium Radioisotopes
• Yttrium-90

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Hematopoietic Stem Cell Transplantation
• Hodgkin Disease (drug therapy)
• Humans
• Neoplasm Recurrence, Local
• Radioimmunotherapy
• Tissue Distribution
• Transplantation Conditioning
• Tumor Microenvironment
• Yttrium Radioisotopes (therapeutic use)