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3270 Tumor Associated Antigen Specific T Cells Given in Combination with Nivolumab for the Treatment of Hodgkin Lymphoma

Program: Oral and Poster Abstracts
Session: 704. Immunotherapies: Poster III
Hematology Disease Topics & Pathways:
Biological, Diseases, Hodgkin Lymphoma, Therapies, CAR-Ts, Combinations, checkpoint inhibitors, Pediatric, B-Cell Lymphoma, immunotherapy, Lymphoid Malignancies, infusion, Study Population, Clinically relevant
Monday, December 7, 2020, 7:00 AM-3:30 PM

Hema Dave, MD, MPH1, Mimi Mai2*, Madeline Terpilowski, BS2*, Keri Toner, MD1, Maja Stanojevic, MD2*, Morgan Galligan, BS2*, Abeer Shibli, BS2*, Melanie Grant, PhD2*, Christopher Lazarski, PhD2*, Philip Y Maglo, BS, MPH2*, Nan Zhang2*, Jay Tanna, MS2*, Richard F. Ambinder, MD3, Martha Glenn, MD4, Patrick Hanley, PhD2* and Catherine M. Bollard, MD, MBChB1

1Children's National Hospital and The George Washington University, Washington, DC
2Program for Cell Enhancement and Technologies for Immunotherapy (CETI), Children's National Hospital, Washington, DC
3Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD
4Division of Hematology and Hematologic Malignancies, University of Utah, Salt Lake City, UT

Background: Hodgkin Lymphoma (HL) Reed Sternberg cells express tumor associated antigens (TAA) that are potential targets for cellular therapies. We recently demonstrated that TAA specific T cells (TAA-T) targeting WT1, PRAME and Survivin were safe and associated with prolonged time to progression in solid tumors (Hont JCO 2019). Hence, we evaluated whether TAA-T cells are safe and elicit anti-tumor effects in patients with relapsed/refractory (rel/ref) HL. We further evaluated the safety of Nivolumab following the TAA-T infusion and its effect on the persistence of the TAA-T cells in vivo.

Methods: TAA-T products were generated from patients or healthy donors on 2 trials (NCT02203903; NCT03843294). Thirteen patients underwent procurement for product generation and 10 patients (2 allogeneic; 8 autologous) were infused TAA-T for rel/ref HL or as consolidation after autologous hematopoietic stem cell transplant (HSCT) at cumulative doses ranging from 0.5 X107 to 4 X107cells/m2. Patients were monitored for six weeks for safety and for response until disease progression. Seven patients received Nivolumab starting at 8 weeks after the first TAA-T infusion until disease progression or unacceptable toxicity.

Results: TAA-T products (n=10) were polyclonal CD3+ T cells (Median 97%; 80.9-99.5%), comprised predominantly of CD4+ helper T cells (Median 10.5%; 1.74-20%) and CD8+ cytotoxic T cells (Median 70%; 29.3-87.5%). Specificity of TAA-T products was tested using Interferon-ϒ(INFϒ)-enzyme-linked immunospot (ELIspot) assay and defined as ≥ 2x spot-forming cells (SFC)/2.5X105cells against the tumor antigen as compared to irrelevant control antigen Actin(Figure 1). The median TAA specificity of the products was 2 antigens (range 0-3). All products were polyfunctional secreting INF-ϒ and TNF-α upon restimulation with tumor antigens (Fig 1).

Median age of patients was 36yrs (range16-53). Patients had received a median 6 lines of therapy including HSCT prior to receiving TAA-T. Median follow-up post TAA-T#1 was 6 months (range 32 days-2.5yrs). There were no dose limiting toxicities observed within the 6 week safety monitoring period. In patients receiving Nivolumab post TAA-T, there were no increased immune related events over expected. One patient had Grade 3 seizures, possibly related to Nivolumab, 2 patients developed hypothyroidism requiring thyroid supplements and one patient developed myositis and discontinued Nivolumab after 5 months. The 2 patients who received TAA-T (1 donor derived and one autologous) as consolidation post HSCT achieved a continued complete remission (CCR) for 2+ years. Of the 8 patients with rel/ref HL at the time of infusion, 1 had disease progression at 6 weeks. He then received Nivolumab off protocol and achieved complete remission (CR) but developed Grade 4 GVHD. The remaining 7 patients had stable disease (SD) at 6 weeks. At a median follow-up of 6 months (32 days-2.5 years), 1 patient had progressive disease(PD) at 3 months, 1 patient had a complete metabolic response at 6 months and proceeded to allogeneic HSCT for definitive cure. 2 patients had PD at 6 months and the other 2 patients continue with SD at 6 months and remain on Nivolumab (Fig 1).

All patients with objective responses (stable disease or better) recovered functional TAA-T cells in the peripheral blood at 3 months as detected by anti-Interferon-ϒ ELISPOT and reported as mean SFC/1 X105 cells for WT1(14±SD18.1); PRAME (17.4±15.3) and Survivin (4.5±7) compared to those with progressive disease with mean SFC/1 X105 cells for WT1 1.4(±2.3); PRAME (6.7±15.5) and Survivin (0.8±1.2). To evaluate TAA-T persistence, unique T cell receptor clonotypes defined in the TAA-T product and not present at baseline were detected in the peripheral blood 6 weeks post TAA-T, long-term persistence data and evaluating the effect on the TCR repertoire when adding nivolumab are pending.

Conclusion: TAA-T cells given in combination with Nivolumab were safe when administered to patients with rel/ref HL with prolonged clinical responses (ranging from SD to CCR) observed in multiply relapsed patients.

Disclosures: Glenn: Genentech: Research Funding. Hanley: Mana Therapeutics: Honoraria, Other: Board Member; Cellevolve: Honoraria, Other: Board(Scientific Advisory Board). Bollard: Mana Therapeutics: Other: IP.

*signifies non-member of ASH