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

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, 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

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.

© 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.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Clinical trial schema and consort diagram.
Figure 2.
Figure 2.
PK of 111In-basiliximab/DOTA in all patients. (A) Clearance of 111In-basiliximab/DOTA from blood over time. (B) Clearance of 111In-basiliximab/DOTA from serum over time. (C) Clearance of 111In-basiliximab/DOTA from urine over time.
Figure 3.
Figure 3.
Biodistribution of 111In-basiliximab/DOTA at 144 hours in UPN-1 (left) and 18F-FDG-PET (right).

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