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2101 Allogeneic Blood or Marrow Transplantation (AlloBMT) with High-Dose Post-Transplantation Cyclophosphamide (PTCy) for Acute Lymphoblastic Leukemia (ALL) in Patients Aged ≥ 55: Best Results in B ALL in First Remission (CR1) with Reduced-Intensity Conditioning (RIC)

Program: Oral and Poster Abstracts
Session: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster I
Hematology Disease Topics & Pathways:
Research, ALL, Lymphoid Leukemias, elderly, Clinical Research, Diseases, Therapies, therapy sequence, real-world evidence, Lymphoid Malignancies, Study Population, Human
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Jonathan Allen Webster, MD1, Madison C Reed, BS2, Hua-Ling Tsai3*, Alexander J. Ambinder, MD, MPH4, Tania Jain, MD5, Amy E. DeZern, MD4, Mark J. Levis, MD6, Margaret M. Showel, MD7*, Gabrielle T. Prince, MD5*, Christopher S. Hourigan, MD PhD5, Javier Bolaños-Meade, MD3, Lukasz P. Gondek, MD, PhD8, Gabriel Ghiaur, MD, PhD9, William Brian Dalton, MD, PhD10, Suman Paul, PhD, MD11, Ephraim J. Fuchs, MD, MBA3, Christian B. Gocke, MD, PhD12, Abbas Abbas Ali, MD13, Douglas E Gladstone, MD3, Carol Ann Huff, MD3, Ivan M. Borrello, MD3, Lode J. Swinnen, MB ChB14, Nina D. Wagner-Johnston, MD9, Richard F. Ambinder, MD, PhD15, Leo Luznik, MD3*, Ivana Gojo, MD3, B. Douglas Douglas Smith, MD16, Ravi Varadhan, PhD3*, Richard J. Jones, MD3 and Philip H. Imus, MD3

1Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD
2Johns Hopkins University, Baltimore, MD
3Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD
4Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD
5The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD
6Director, Adult Leukemia Program, Co-Division Director, Hematologic Malignancies, Professor of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, MD
7Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD
8Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD
9Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD
10Johns Hopkins Hospital, Baltimore, MD
11Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Toledo, OH
12Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins/Sidney Kimmel Cancer Center, Baltimore, MD
13Sidney Kimmel Comprehensive Cancer Center, John's Hopkins Hospital, Baltimore, MD
14Division of Medical Oncology, Johns Hopkins Cancer Center, Baltimore, MD
15Sidney Kimmel Cancer Center at Johns Hopkins, Baltimore, MD
16Sidney Kimmel Comprehensive Cancer Center, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD

Background: Older patients with ALL fare poorly with conventional chemotherapy. Patients aged 55-65 on E2993 and ≥ 60 treated with Hyper-CVAD have 5-year overall survival (OS) of just 21% and 20%, respectively (Sive. BJH. 2012 and O’Brien. Cancer. 2008). Recently, HyperCVD with inotuzumab +/- blinatumomab in patients ≥ 60 years old with Ph- B ALL demonstrated an improved 5-year OS of 47% with 38% of patients dying in remission (Short. Blood. 2021). AlloBMT provides an alternative consolidation strategy. Registry studies in ALL patients ≥ 60 years old and B ALL patients ≥ 55 years old who underwent alloBMT with RIC in CR1 demonstrated 5 and 3-year OS of 42% and 45%, respectively (Roth-Guepin. Oncotarget. 2017 and Rosko. Am J Hematol. 2017). These studies utilized heterogenous conditioning and graft-versus-host disease (GVHD) prophylaxis regimens. The use of high-dose post-transplantation cyclophosphamide as GVHD prophylaxis facilitates transplants in older adults with low rates of non-relapse mortality, GVHD, and the use of HLA haploidentical donors (Kasamon. JCO. 2015).

Methods: The bone marrow transplant database at Johns Hopkins was queried for patients ≥ 55 years old who received a first alloBMT using PTCy from January 2008-January 2021. Characteristics of patients were summarized and compared using Fisher's exact test for categorical variables. Estimators of OS and relapse-free survival (RFS) were reported using the Kaplan-Meier method. Differences in time-to-event outcomes were estimated using Cox proportional hazards model, or Fine and Gray’s model for cumulative incidence of relapse (CIR)/nonrelapse mortality (NRM) considering competing risks.

Results: A total of 77 patients aged ≥ 55 underwent a first alloBMT with PTCy for ALL. The vast majority were performed in CR1 (85.7%), utilized RIC (88.3%), and were performed for B ALL (90.9%). Demographics and transplant characteristics are presented in Table 1. RIC consisted of fludarabine, cyclophosphamide and total body irradiation followed by PTCy-based GVHD prophylaxis as previously described (Kasamon. BBMT. 2008).

Relapse-free survival (RFS) and OS at 5 years for the entire cohort were 46% (95% CI 34-57) and 49% (95% CI 37-60), respectively, with a 5-year CIR of 27% (95% CI 18-38) and NRM of 28% (95% CI 18-39). The cumulative incidences of grade 3-4 acute GVHD at 1 year and chronic GVHD at 3 years were 3% (95% CI, 0% to 9%) and 13% (95% CI 5% to 21%), respectively. In univariate analysis, the use of myeloablative conditioning led to worse RFS (HR 0.25, p=0.0004); while the absence of MRD (HR 2.93, p=0.008), transplant in CR1 (HR 3.81, p=0.0004), and transplant for Ph+ ALL vs. T ALL (HR 3.15, p=0.03) led to improved RFS.

Subsequent analysis focusing on the 54 patients receiving RIC alloBMT in CR1 for B ALL demonstrated RFS and OS at 5 years of 61% (95% CI 46-73) and 64% (95% CI 49-76), respectively, (see Figure 1) with a 5-year CIR of 16% (95% CI 7-27) and NRM 24% (95% CI 13-36), although just 7% at 1 year. For B ALL patients transplanted with RIC in CR1, 3-year NRM was higher among patients who received a peripheral blood stem cell transplant (55%, 95% CI 18% to 81%), those treated with rituximab pre-transplant (36%, 95% CI 16% to 57%), and those who received ≥100 mg/m2 of doxorubicin equivalent for ALL (67%, 95% CI 19% to 90%). Outcomes did not differ among the 20% of patients who received pre-transplant blinatumomab compared to those who did not. Among the 23 Ph+ B ALL patients transplanted with RIC in CR1 following treatment with a 2nd or 3rd generation tyrosine kinase inhibitor (TKI), the 5-year CIR was 5% (95% CI, 0% to 22%).

Conclusions: RIC AlloBMT with PTCy in CR1 represents a promising consolidation strategy for B ALL patients ≥ 55 years old.

Disclosures: Webster: Amgen: Consultancy; Pfizer: Consultancy. Jain: Care Dx, Bristol Myers Squibb, Incyte, Abbvie, CTI, and Kite: Other: Advisory Board participation; CTI Biopharma, SyneosHealth, Incyte: Research Funding. DeZern: Gilead: Consultancy, Honoraria; GERON: Other: DSMB; Bristol Myers Squibb: Consultancy, Honoraria; CTI BioPharma: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Syntrix Pharmaceuticals: Research Funding. Levis: Astellas, and FujiFilm: Research Funding; AbbVie, Amgen, Astellas, Bristol Myers Squibb, Daiichi-Sankyo, FujiFilm, Jazz Pharmaceuticals, and Menarini: Consultancy. Hourigan: Sellas Life Sciences (Inst): Research Funding; Archer Diagnostics: Other; Qiagen: Other; TwinStrand Biosciences: Other; Mission Bio: Other. Ghiaur: Syros Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Menarini Group: Consultancy, Research Funding; Scripps: Consultancy, Research Funding. Fuchs: Iyuda Therapeutics, LLC: Consultancy, Current Employment, Other: Co-Founder. Huff: Sanofi: Research Funding; Janssen: Research Funding; Oncopeptides: Research Funding; Glaxo Smith Kline: Research Funding; Prothena: Current equity holder in publicly-traded company. Luznik: WindMil Therapeutics: Patents & Royalties; Genentech: Other: Clinical Trial support, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rubius Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Precision Biosciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Talaris Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Gojo: Ono Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Clearview: Membership on an entity's Board of Directors or advisory committees; Certara: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Immunogen: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Research support; Genentech: Other: Research support; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Research support; Amphivena: Other: Research Support; Merck: Other: Research support; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Research Support; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees. Smith: Pfizer: Consultancy; BMS: Consultancy; Servier: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Novarits: Consultancy.

*signifies non-member of ASH