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2017 Consolidation with Allogeneic Hematopoietic Cell Transplant Improved Survival Outcomes of Adults with Relapsed / Refractory Acute Lymphoblastic Leukemia Following Response to Memory-Enriched CD19CAR T Cells

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster I
Hematology Disease Topics & Pathways:
Biological therapies, adult, Clinical Practice (Health Services and Quality), Chimeric Antigen Receptor (CAR)-T Cell Therapies, Therapies, Study Population, Human
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Ibrahim Aldoss, MD1,2,3, Samer Khaled, MD4*, Xiuli Wang, MD PhD5, Joycelynne Palmer, PhD6*, Yan Wang, MS7*, Jamie R Wagner, BS8*, Mary C. Clark, PhD9*, Jennifer Simpson10*, Jinny Paul, PhD11*, Vibhuti Vyas, MS2*, Sheng-Hsuan Chien12*, Anthony S. Stein, MD13,14, Vinod A. Pullarkat, MD15*, Amandeep Salhotra, MD3,16, Monzr M. Al Malki, MD13, Sandra Thomas, PhD9, Elizabeth L. Budde, MD, PhD17, Guido Marcucci, MD18, Christine E Brown, PhD19* and Stephen J Forman, MD3,13

1City of Hope, Duarte, CA
2Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
3Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA
4Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
5Department of Hematology and Hematopoietic Cell Transplantation, City of Hope Comprehensive Cancer Center, Duarte, CA
6Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope, Duarte, CA
7Department of Computational and Quantitative Sciences, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
8T Cell Therapeutics Laboratory, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
9Department of Clinical and Translational Project Development, City of Hope, Duarte, CA
10City of Hope National Medical Center, Duarte, CA
11T Cell Therapeutics Laboratory, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte
12Department of Hematology and Hematopoeitic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
13Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA
14Gehr Family Leukemia Center, City of Hope, Duarte, CA
15Department of Hematology and Hematopoietic Cell Transplantation and Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, CA
16Department of Hematology and HCT, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA
17Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
18Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA
19T-Cell Therapeutics Research Laboratory, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA

Background: CD19-directed chimeric antigen receptor (CD19CAR) T cell therapy produces excellent remission rates in children and adults with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL). While a small number of adult patients (pts) who respond to CD19CAR T cells have durable remission without additional therapy, most do not, and it remains debatable whether consolidation with allogeneic hematopoietic cell transplantation (alloHCT) after CD19CAR T cells should be offered to every adult responder with r/r ALL, especially in context of a second consolidative alloHCT in pts who relapsed following prior alloHCT. Here we report a subanalysis from our recently completed phase 1/2 prospective study (NCT02146924) using memory-enriched CD19CAR T cells in adults with r/r ALL to assess the role of alloHCT consolidation on outcome.

Methods: This study assessed the safety and efficacy of naïve, stem and central memory (Tn/mem)-derived CAR T cells delivered at the recommended phase 2 dose (RP2D; 200x106 CAR T cells) in adults with r/r ALL. If pts achieved complete remission (CR)/CR with incomplete hematologic recovery (CRi) post CAR T cells, they could receive optional consolidation with alloHCT per the treating physician discretion anytime 4 weeks after infusion. We evaluated the adjusted association between relapse free survival (RFS) and time varying status for alloHCT consolidation, Philadelphia (Ph)-like status, bone marrow blasts at time of lymphodepletion (LD; <5% vs. ≥5%) and presence of extramedullary disease (EMD) at LD among the responders by performing a pre-specified Cox proportional hazards regression model.

Results: We enrolled 58 pts at the RP2D who underwent leukapheresis; 46 pts received CD19CAR T cells. The median age for pts who received CD19CAR T cells was 38 years (range, 22-72), with 15 (33%) pts ≥ 50 years. The median number of prior lines of therapy was 3 (range, 1-9); 29 (63%) pts had prior alloHCT, and 29 (63%) and 15 (33%) pts failed blinatumomab and inotuzumab before enrollment, respectively. Eighteen (39%) had Ph-like genotype and 16 (35%) had EMD at LD. Forty (87%) patients achieved CR/CRi, 1 (2%) progressed and 5 (11%) were unevaluable for response.

Twenty-one (53%) responders proceeded directly to alloHCT consolidation while in CR/CRi post CAR T cell therapy, including 10 pts who received their second alloHCT. Notably, 6/13 pts with EMD at LD who achieved CR/CRi after infusion underwent alloHCT consolidation. The median time to transplant was 79 days (range, 50-192) post CAR T cell infusion. For the 40 responders, with a median follow up of 11.4 months (range, 3.3-65.8) post CAR T cell infusion, median overall survival (OS) was not reached, and median RFS was 17.1 months (95%CI: 6.9 to NA). The 12-month OS and RFS were 63.2% and 52.6%, respectively.

Among responders, 12-month RFS were 81% and 16% for those who did and those who did not undergo consolidation with alloHCT in CR/CRi, respectively. In the prespecified multivariable analysis, only consolidation with alloHCT post CAR T cells was independently associated with superior RFS [adjusted hazard ratio (HR)=0.16; 95% CI: 0.05-0.48; P= 0.001]. Of the 19 pts who responded to CAR T cells and did not have alloHCT consolidation, 11 relapsed with a median time of 3.4 months (range, 2.1-10.3) post CAR T cell infusion, 3 pts died in remission, and 5 pts remained alive and in remission at last contact or date of censoring, with a median follow up of 9.7 months (range, 3.3-51.8) including 1 pt who was censored at day 99 post infusion upon initiating ponatinib maintenance. Of the 21 pts who responded to CAR T cells and underwent alloHCT consolidation, 2 pts relapsed (6.9- and 12.4-months post-transplant) of whom 1 died after relapse and 1 received a second CAR T cell infusion and was censored for OS at the date of second infusion, 3 pts died in remission, and 16 pts remained alive and in remission. (Figure A) The 100-day non-relapse mortality rate post-transplant was 5% (n= 1). OS was comparable for responders who had their first or second alloHCT post CAR T cells (12-months OS= 82% vs 79%, p= 0.9; Figure B).

Conclusion: Outcomes of alloHCT consolidation in adults with high-risk r/r ALL after achieving remission with Tn/mem CD19CAR T cells were promising, including for pts receiving their second alloHCT, and transplant led to improved survival outcomes.

Disclosures: Aldoss: Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; MacroGenics: Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Autolus: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Stein: Amgen: Speakers Bureau. Pullarkat: Amgen, Dova, and Novartis: Consultancy, Other: Advisory Board Member; AbbVie, Amgen, Genentech, Jazz Pharmaceuticals, Novartis, Pfizer, and Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Salhotra: BMS: Research Funding; Kadmon: Other: Advisory board meeting ; Orca Bio: Research Funding. Al Malki: NexImmune: Consultancy, Research Funding; Hasna Biopharma: Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotec: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; CareDx: Consultancy, Research Funding; Gilead: Consultancy, Research Funding. Budde: Mustang Therapeutics: Research Funding; AstraZeneca: Research Funding; Amgen: Research Funding; Amgen: Research Funding; Merck: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ziopharm: Other: DMSC member for a phase 1 clinical; BeiGene: Membership on an entity's Board of Directors or advisory committees. Marcucci: Agios: Other: Speaker and advisory scientific board meetings; Abbvie: Other: Speaker and advisory scientific board meetings; Novartis: Other: Speaker and advisory scientific board meetings. Brown: Mustang Bio: Consultancy, Other: IP licensing revenue; Chimeric Therapeutics: Consultancy, Other: IP licensing revenue.

*signifies non-member of ASH