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Regular and Young Investigator Award Abstracts
Clinical Trial In Progress
686 Targeted immunotherapy and checkpoint blockade in children, adolescents, and young adults with lymphoma: RADICAL hodgkin cohort
  1. Kayleigh Klose1,
  2. Jessica C Hochberg2,
  3. Jaclyn Baso2,
  4. Ana C Xavier3,
  5. Anthony N Audino4,
  6. Matthew Barth5,
  7. Rodney Miles6,
  8. Samir Kahwash4,
  9. Stephan D Voss7,
  10. Suzanne Braniecki2,
  11. Chitti Moorthy2,
  12. Saro Armenian8,
  13. Matthew Ehrhardt9,
  14. Megan S Lim10,
  15. Lauren Harrison2,
  16. Arvind Budhram2,
  17. Ariel Stonberg2,
  18. Stanton Goldman11 and
  19. Mitchell S Cairo12
  1. 1Westchester Medical Center, White Plains, NY, USA
  2. 2New York Medical College, Valhalla, NY, USA
  3. 3University of Alabama at Birmingham, Birmingham, AL, USA
  4. 4Nationwide Children’s Hospital, The Ohio State University, Columbus, OH, USA
  5. 5University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
  6. 6University of Utah, Salt Lake City, UT, USA
  7. 7Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
  8. 8City of Hope, Duarte, CA, USA
  9. 9St. Jude Children’s Research Hospital, Memphis, TN, USA
  10. 10University of Pennsylvania, Philadelphia, PA, USA
  11. 11Medical City Children’s Hospital, Dallas, TX, USA
  12. 12New York Medical College At Maria Fareri Children’s Hospital, Valhalla, NY, USA

Abstract

Background Significant chronic health conditions continue to increase over time among pediatric, adolescent, and young adult (CAYA) classical Hodgkin lymphoma (cHL) survivors. Targeting the tumor microenvironment (TME) and tumor-specific antigens are emerging as effective and safe treatments for cHL patients which may help reduce toxicity. Recently, we completed a phase 2 trial evaluating the use of an antibody-drug conjugate targeting CD30 (brentuximab vedotin, Bv) and an anti-CD20 antibody targeting regulatory B-cells (rituximab, RTX) added to risk-adapted chemotherapy in newly diagnosed cHL CAYA patients. The combination was safe and resulted in significant reduction to toxic chemotherapy and radiation therapy (RT), while keeping superior outcomes (5-year OS/EFS 100%).1 Adding the checkpoint inhibitor nivolumab to chemoimmunotherapy with RTX + Bv may allow further anthracycline dose reduction and reduce the need for RT in intermediate-/high-risk cHL in CAYA.

Methods This is a multicenter study for patients with intermediate- and high-risk cHL. Intermediate-risk cHL patients receive 2 cycles of Bv, doxorubicin, vinblastine, dacarbazine, and RTX (Bv-AVD-R). Rapid early responders (RER, complete metabolic response) or slow early responders (SER, incomplete metabolic response) by FDG-PET interim scan receive 2 or 4 cycles of Bv, vinblastine, dacarbazine, nivolumab, and RTX (Bv-NVD-R), respectively without further anthracycline. High-risk cHL patients receive 2 cycles of Bv-AVD-R. RERs by FDG-PET scan receive 4 cycles of Bv-NVD-R; SERs receive 2 cycles of Bv, nivolumab, doxorubicin, vinblastine, dacarbazine and RTX (Bv-NAVD-R), followed by 4 cycles of Bv-NVD-R. RT will only be given to patients not achieving complete remission (CR) at the end of therapy.

Results Twelve patients have been enrolled to date including 5 intermediate- and 7 high-risk patients. Three intermediate- and 5 high-risk patients have completed interim imaging studies. All intermediate-risk patients and 3 high risk patients have achieved a CR (RER). Two high-risk patients had a partial response (SER). Both SER patients achieved a CR following the 6 additional cycles of chemotherapy as detailed above. No patients have required radiation therapy. There have been no dose limiting toxicities. Accrual is ongoing.

Conclusions Targeting the Hodgkin Reed-Sternberg cell as well as the TME (regulatory B-cells) and PD1/PD-L1 axis is a promising approach in CAYA with cHL. (NCT05253495).

Trial Registration Clinicaltrials.gov, NCT05253495

Reference

  1. Hochberg J, Basso J, Shi Q, Klejmont L, Flower A, Bortfeld K, Harrison L, van de Ven C, Moorthy C, Islam H, Gerard P, Voss S, Cairo MS. Risk-adapted chemoimmunotherapy using brentuximab vedotin and rituximab in children, adolescents, and young adults with newly diagnosed Hodgkin’s lymphoma: a phase II, non-randomized controlled trial. J. Immunother. Cancer. 2022;10:e004445.

Ethics Approval This study was approved by New York Medical College’s Ethics Board; approval number 14601.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/jitc-2023-SITC2023.0686

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