Accelerate ALCL- Nivolumab With Vinblastine and Brentuximab Vedotin for High Risk Relapsed ALK+ ALCL

Authors

• David Hoogstra, Corewell Health West
• Ana C. Xavier
• Allyson Flower
• Anthony Audino
• Jessica Hochberg
• Xiaokui Mo
• Rodney R. Miles
• Suzanne Turner
• Stephan D. Voss
• Lauren Harrison

Document Type

Conference Proceeding

Publication Date

4-2026

Publication Title

Pediatric Blood & Cancer

Abstract

Background: Anaplastic large cell lymphoma (ALCL) represents10%–15% of pediatric Non-Hodgkin lymphoma. Despite the use of multiple therapeutic regimens combining aggressive multi-agent chemotherapy, brentuximab vedotin (BV), and ALK inhibition over the past 30 years, relapse rates remain at 20%–30%. For patients with relapsed or refractory disease, the optimal treatment and the biological variables associated with response or resistance to therapy are unknown. The majority of pediatric ALCL harbors oncofusions containing the anaplastic lymphoma kinase (ALK)which induces STAT3 activation and leads to the expression of the immunosuppressive programmed death ligand 1 (PD-L1).The NIVO-ALCL trial evaluated single agent PD-1 inhibition (nivolumab) in patients with relapsed or refractory ALK+ ALCL and demonstrated no severe or unexpected side effects, with an overall response rate of 50% and a 2-year progression free survival of only 17%. These results demonstrate that nivolumab is an active agent in ALK+ ALCL, but is not curative monotherapy.

Objectives: The ACCELERATE ALCL trial (NCT07013565)(IND177155) is a multi-arm, open-label, nonrandomized, multicenter phase 2 trial evaluating the safety and efficacy of nivolumab-based combinatorial re-induction immunotherapy, followed by consolidation with reduced toxicity conditioning (RTC) and allogeneic stem cell transplantation (AlloSCT) inpatients with relapsed or refractory ALK+ ALCL.

Design/Method: Trial participants are risk stratified as low risk (first relapse, relapse greater than 1 year from diagnosis, common histology, and no prior vinblastine (VBL) therapy) or high risk (not meeting low risk criteria). The trial design schema is shownin Figure 1. In brief, low risk participants are treated with VBL monotherapy for up to 2 years if they achieve a complete response(CR). High risk participants are initially treated with nivolumab combined with either BV or VBL based on their prior therapy.

After 2 cycles of therapy, participants not in CR proceed with 2 additional cycles of nivolumab combined with BV and VBL. After 2 cycles of this therapy, participants not in CR proceed with ifosfamide, carboplatin, and etoposide (ICE). After ICE, participants not in a CR or partial response (PR) are off protocol therapy. Participants that achieve CR at any time, or a CR or PR after ICE will proceed with RTC AlloSCT. Extensive correlative biology studies are planned.

Results: This trial is actively enrolling at multiple clinical sites inthe United States.

Conclusion: ACCELERATE ALCL is investigating the safety andefficacy of nivolumab in combination with BV and VBL followedby RTC and AlloSCT in participants with relapsed or refractory ALK+ ALCL.

Volume

73

Issue

Suppl 2

First Page

s157

Comments

American Society of Pediatric Hematology/Oncology(ASPHO) Conference, April 29-May 2, 2026, Minneapolis, MN

Helen DeVos Children’s Hospital

Last Page

s158

Recommended Citation

Hoogstra D, Xavier AC, Flower A, Audino A, Hochberg J, Mo X, et al. Accelerate ALCL- nivolumab with vinblastine and brentuximab vedotin for high risk relapsed ALK+ ALCL. Pediatr Blood Cancer. 2026;73(Suppl 2):s157-s8. doi: 10.1002/1545-5017.70343.

DOI

10.1002/1545-5017.70343

ISSN

1545-5009