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3582 A Phase IB/II Study of Blinatumomab in Patients with B-Cell Acute Lymphoblastic Leukemia (ALL) and B-Cell Non-Hodgkin Lymphoma (NHL) As Post-Allogeneic Blood or Marrow Transplant (alloBMT) Remission Maintenance

Program: Oral and Poster Abstracts
Session: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphoid Leukemias, ALL, Biological therapies, Lymphomas, non-Hodgkin lymphoma, Bispecific Antibody Therapy, Clinical Research, B Cell lymphoma, Diseases, Therapies, Immunotherapy, Lymphoid Malignancies, Transplantation
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Jonathan Allen Webster, MD1, Richard J. Jones, MD2, Amanda Blackford2*, Audra Shedeck2*, Richard F. Ambinder, MD3, Lode J. Swinnen4, Nina Wagner-Johnston, MD5, Ephraim Joseph Fuchs, MD, MBA2, Javier Bolanos-Meade, MD, KHS6*, Philip Imus, MD7, Challice L. Bonifant, MD, PhD8, Heather Jill Symons, MD5*, Tania Jain, MD2, Gabrielle T. Prince, MD2*, Mark J. Levis, MD, PhD9, Leo Luznik, MD10 and Ivana Gojo, MD7

1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD
2Johns Hopkins University, Baltimore, MD
3Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD
4Johns Hopkins Cancer Center, Baltimore, MD
5Johns Hopkins Hospital, Baltimore, MD
6Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD
7Johns Hopkins, Baltimore, MD
8Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
9Division of Hematologic Malignancies, Johns Hopkins University, Baltimore, MD
10Sidney Kimmel Comprehensive Cancer Ctr., Baltimore, MD

Background: AlloBMT can be curative as consolidation for high risk B ALL and NHL. However, transplant-related toxicity and disease relapse limit survival. Post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis limits GVHD and facilitates alternative allograft sources. Following PTCy, cellular immune reconstitution is favorable for strategies to augment anti-tumor immunity. Blinatumomab (blina) is effective in the treatment of CD19+ ALL and NHL. Blina leads to T cell activation that may enhance post-transplant tumor-specific T cell responses, leading to a more potent graft-versus-tumor effect. A study of 21 B ALL pts demonstrated the feasibility of post-transplant blina but did not improve survival when pts universally remained on immunosuppression for at least 1 cycle of treatment (Gaballa. Blood. 2022). We present results of a phase Ib/II trial to assess the tolerability and preliminary efficacy of blina as post-alloBMT remission maintenance in B-cell ALL and NHL in pts off immunosuppression.

Methods: Pts ≥1 month-old with high risk CD19+ B ALL or ≥18 years-old with NHL who underwent alloBMT with PTCy were eligible. Pts had to be 60-180 days post-transplant with count recovery and in remission. Pts had to be off immunosuppression for ≥4 weeks prior to treatment, and without a history of grade ≥3 acute GVHD or severe chronic GVHD. Pts could receive 2 cycles of blina if they had evidence of disease (including MRD) at their pre- and/or post-transplant evaluations but otherwise received 1 cycle. Blina was given as a continuous infusion at 9 mcg/day on C1D1-7 and 28 mcg/day on C1D8-28 and C2D1-28.

Results: The study closed to accrual on January 31, 2023 following enrollment of 42 pts (26 male/16 female) with a median age of 54 (Range 30-73). Among enrolled pts, 19 had Ph-negative B ALL and 23 had B-cell NHL. All pts underwent reduced-intensity conditioning alloBMT using a regimen of fludarabine, cyclophosphamide, and total body irradiation. Median prior lines of therapy were 2 (range 1-6). Additional transplant details are presented in Table 1. All B ALL pts were in an MRD-negative CR by flow cytometry at a sensitivity of 0.01% at alloBMT. All pts received a single cycle of therapy. Pts started blina a median of 137 days post-transplant (range, 90-182). Four pts failed to complete a full cycle due to G4 transaminitis (1), G4 neutropenia (1), relapse (1), and patient preference in the setting of tremors (1). Grade 3 or 4 adverse events felt to be at least possibly related to the study drug included G3 neutropenia (7%), G4 neutropenia (19%), anemia (5%), G3 ALT (5%), G4 AST (2%), G3 AST (2%), and neurotoxicity (7%). Two pts (5%) developed chronic GVHD following blina requiring the resumption of immunosuppression. At a median follow-up of 40 months post-alloBMT, the 3-year relapse-free survival is 73% (95% CI 54-85%) due to a 24% (95% CI 12-39%) incidence of relapse and a 4% (95% CI 0-17%) incidence of non-relapse mortality, as shown in Figure 2. All 3 (100%) relapsed B ALL pts and 2/6 (33%) relapsed B NHL pts presented with CNS involvement. Four pts with CNS relapse (80%) had CNS involvement prior to alloBMT. Among 2 pts who died without relapse, 1 was unrelated to alloBMT, while the other died of therapy-related myeloid neoplasm. Data on biomarkers including changes in T cell subpopulations in both BM and PB, and co-signaling molecule expression will be presented.

Conclusions: Post-alloBMT maintenance therapy with blina is feasible with minimal toxicity in pts off immunosuppression. Initial survival outcomes are promising with the majority of relapses involving the CNS. A randomized trial of maintenance with blina after alloBMT with PTCy is needed to confirm efficacy in this high-risk population.

Disclosures: Webster: Pfizer: Consultancy; Servier: Consultancy. Wagner-Johnston: Astex: Research Funding; Genentech: Research Funding; Beigene: Consultancy, Research Funding; ADC Therapeutics: Research Funding; Merck: Research Funding. Bonifant: NA: Other: Patents pending on use of engineered cellular therapies for cancer; Sharpe: Research Funding; Bristol Myers Squibb: Research Funding; Merck: Research Funding; Dohme, Inc.: Research Funding. Jain: CTI Biopharma, Kartos therapeutics, Incyte: Research Funding; Care Dx, Bristol Myers Squibb, Incyte, Abbvie, CTI, Kite, Cogent Biosciences, Blueprint Medicine, Telios pharma, Protagonist therapeutics: Membership on an entity's Board of Directors or advisory committees. Levis: Astellas Global Pharma: Research Funding; Abbvie: Consultancy; Amgen: Consultancy; Bristol Myers Squibb: Consultancy; Daiichi-Sankyo: Consultancy; Jazz: Consultancy; Menarini: Consultancy; Takeda: Consultancy; FujiFilm: Research Funding; Pfizer: Consultancy. Luznik: Gilead Sciences: Consultancy; Precision Biosciences: Consultancy; Rubius Therapeutics: Consultancy; Talaris Therapeutics: Consultancy; WindMiL therpeutics: Patents & Royalties; Genentech: Research Funding. Gojo: Merck: Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Incyte: Research Funding; Nkarta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Scimentum: Consultancy, Membership on an entity's Board of Directors or advisory committees; MJH Healthcare Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees; Clearview: Consultancy, Membership on an entity's Board of Directors or advisory committees.

OffLabel Disclosure: Blinatumomab as post-alloBMT maintenance for patients in remission

*signifies non-member of ASH