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495 Survival Following Post-HCT Relapse in Adult Acute Lymphoblastic Leukemia Has Improved in the Era of Novel Immunotherapies: A Single Institution Analysis

Program: Oral and Poster Abstracts
Type: Oral
Session: 723. Clinical Allogeneic and Autologous Transplantation: Late Complications and Approaches to Disease Recurrence II
Hematology Disease Topics & Pathways:
ALL, Adult, Biological, Leukemia, Diseases, CAR-Ts, Lymphoid Malignancies, Study Population
Sunday, December 6, 2020: 3:00 PM

Juliana Craig, BA1*, Maria Iglesias, BS1*, Kristen Cunanan, PhD2*, Sally Arai, MD, MS3, Matthew J. Frank, MD, PhD3, Laura J. Johnston, MD3, Robert Lowsky, MD, FRCP3, Everett H Meyer, MD, PhD3*, David B. Miklos, MD, PhD3, Robert S. Negrin, MD3, Andrew R. Rezvani, MD3, Judith A Shizuru, MD, PhD3, Surbhi Sidana, MD4, W-K Weng, MD, PhD5, Parveen Shiraz, MD3 and Lori Muffly, MD, MS6

1Stanford University School of Medicine, Stanford, CA
2Stanford Medicine Quantitative Sciences, Palo Alto, CA
3Division of Blood and Marrow Transplantation, Stanford University, Stanford, CA
4Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA
5Division of Blood and Marrow Transplantation, Dept. of Medicine, Stanford Univ. School of Med., Stanford, CA
6Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA

Background: Historically, the survival of adult patients with acute lymphoblastic leukemia (ALL) relapsing after allogeneic hematopoietic cell transplantation (HCT) was dismal, with fewer than 10% surviving long-term (Fielding et al Blood 2007). In the last five years, the availability of targeted immunotherapies including blinatumomab (blin), inotuzumab ozogamicin (IO), and chimeric antigen T-cell receptor (CART) therapy has expanded the opportunity for effective salvage of relapsed/refractory ALL. We hypothesized that the expanding therapeutic landscape has resulted in superior survival following post-HCT relapse in adult ALL in the targeted immunotherapy era.

Methods: We performed a retrospective analysis of adults receiving first allogeneic HCT for ALL between 2008-2019 at Stanford University; patients were stratified by time period of HCT: 2008-2013 (earlier era) vs 2014-2019 (recent immunotherapy era). Descriptive statistics characterized the study cohort; chi-square test was used to evaluate differences in characteristics and treatments based on time period transplanted. Kaplan Meier method was used to determine overall survival (OS); log-rank tested significance between time periods. Follow-up time of the earlier time period was truncated to 5.4 years to match maximum follow-up time of the more recent time period.

Results: Of the 285 adult ALL patients transplanted (N=119, 2008-2013; N=166, 2014-2019), 81 (28%) experienced disease relapse following HCT and represent the analytic cohort. Post-HCT relapse occurred in 39 (33%) transplanted between 2008-2013 and 42 (25%) transplanted between 2014-2019. The median time to relapse following HCT was 7.72 months (95% CI, 3.88-14.0), and did not significantly differ between time periods. Baseline patient and transplant characteristics were similar across the two time periods (Table 1); however, relative to the earlier time period, patients transplanted during the more recent time period were less likely to be transplanted with active disease (26% vs 2%), and more likely to receive cord blood as a stem cell source (0 vs 10%). The median overall survival (OS) for the entire cohort following post-HCT relapse was 9.93 months (95% CI, 7.07-12.73). However, the median OS from relapse was 7.99 months (95% CI, 3.30-11.6) for patients transplanted in the earlier era, while the median OS for patients relapsing in the recent era was 15.75 months (95% CI, 9.24-26.4), P<0.0001 (Figure 1A). Relative to the earlier era, the use of novel therapies for relapse following HCT increased markedly (44% vs 3%), while the use of traditional chemotherapy dropped (70% vs 38%), P<0.001 across therapies during the two time periods based on year of relapse (Figure 1B). Of the novel therapies administered, blin, IO, and CART were used with descending frequency (64%, 41%, 36%, respectively), and 8 patients received at least two novel therapies after relapse. The frequency of patients receiving no therapy for relapse decreased in the more recent time period (18% vs 10%). Donor lymphocyte infusion (DLI) was administered infrequently during both the early (6%) and more recent time periods (2%), and only two patients in the entire study cohort received a second HCT after relapse.

Conclusion: In this large cohort of adults transplanted for ALL over the last decade, we show that the OS of ALL patients relapsing after HCT has significantly improved, coinciding with a substantial increase in the availability and utilization of novel therapies in this setting. Additional studies are needed to understand the optimal therapeutic intervention for post-HCT relapse in adult ALL.

Disclosures: Meyer: Orca Bio: Research Funding. Miklos: Adaptive Biotech: Consultancy, Other: Travel support, Research Funding; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Allogene Therapeutics Inc.: Research Funding; Novartis: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Janssen: Consultancy, Other: Travel support; Miltenyi Biotec: Research Funding. Negrin: UpToDate: Honoraria; Biosource: Current equity holder in private company; Amgen: Consultancy; BioEclipse Therapeutics: Current equity holder in private company; Magenta Therapeutics: Consultancy, Current equity holder in publicly-traded company; KUUR Therapeutics: Consultancy. Rezvani: Pharmacyclics: Research Funding. Shizuru: Jasper Therapeutics, Inc: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Sidana: Janssen: Consultancy. Shiraz: ORCA BioSystems: Research Funding; Kite, a Gilead Company: Research Funding. Muffly: Servier: Research Funding; Adaptive: Research Funding; Amgen: Consultancy.

*signifies non-member of ASH