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779 Assessment of Outcomes of Allogeneic Stem Cell Transplantation By Treatment Arm in Newly Diagnosed Measurable Residual Disease Negative Patients with B-Lineage Acute Lymphoblastic Leukemia Randomized to Conventional Chemotherapy +/- Blinatumomab in the ECOG-ACRIN E1910 Phase III National Clinical Trials Network Trial

Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Novel Approaches to Risk Stratification and Optimization for Transplant
Hematology Disease Topics & Pathways:
Research, Clinical trials, Lymphoid Leukemias, ALL, Bispecific Antibody Therapy, Clinical Research, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Measurable Residual Disease , Transplantation (Allogeneic and Autologous)
Monday, December 9, 2024: 11:30 AM

Michaela Liedtke, MD1, Zhuoxin Sun, PhD2*, Mark R. Litzow, MD3, Ryan J Mattison, MD4, Elisabeth Paietta, PhD5*, Kathryn G. Roberts6*, Yanming Zhang, MD7, Janis Racevskis, PhD8*, Hillard M. Lazarus, MD9, Jacob M. Rowe, MD10, Daniel A. Arber, MD11, Julie Bergeron, MD12*, Brent L. Wood, MD, PhD13, Yaqi Zhao, MSc14*, Gang Wu, PhD14*, Ti-Cheng Chang, PhD14*, Wenchao Zhang, PhD14*, Keith W. Pratz, MD15, Shira N. Dinner, MD16, Noelle Frey, MD, MS17, Steven D. Gore, MD18, Bhavana Bhatnagar, DO19, Ehab L. Atallah, MD20, Geoffrey L. Uy, MD21, Deepa Jeyakumar, MD22, Tara L. Lin, MD23, Cheryl L. Willman, MD24*, Daniel J. DeAngelo, MD, PhD25, Shejal B. Patel, DO26, Michelle A Elliott, MD24, Anjali S. Advani, MD27, Dimitrios Tzachanis, MD, PhD28, Pankit Vachhani, MD29*, Rupali Bhave, MD30*, Elad Sharon, MD, MPH31*, Richard F. Little, MD, MPH32, Harry P. Erba, MD, PhD33, Richard M. Stone, MD25, Selina Luger, MD, FRCPC34, Charles G. Mullighan, MBBS, MSc, MD6, Martin S. Tallman, MD35 and Matthew J. Wieduwilt, MD36*

1Stanford University Cancer Center, Stanford, CA
2Dana-Farber Cancer Institute, Boston, MA
3Division of Hematology, Mayo Clinic, Rochester, MN
4Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI
5Department of Oncology, Montefiore Medical Center, Bronx, NY
6Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN
7Cytogenetics Laboratory, Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
8Montefiore Medical Center, Bronx, NY
9Case Western Reserve University, Cleveland, OH
10Shaare Zedek Medical Center, Jerusalem, Israel
11University of Chicago, Chicago, IL
12Hopital Necker Enfants Malades, Paris, FRA
13Department of Laboratory Medicine, Seattle Cancer Care Alliance, Los Angeles, CA
14St. Jude Children's Research Hospital, Memphis, TN
15Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA
16Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL
17University of Pennsylvania, Philadelphia, PA
18National Cancer Institute, National Institutes of Health, Rockville, MD
19West Virginia University, Wheeling Hospital, Wheeling, WV
20Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI
21Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO
22Department of Medicine, Division of Hematology Oncology, Chao Family Comprehensive Cancer Center, University of California Irvine Health, University of California Irvine, Orange, CA
23Division of Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Cancer Center, Westwood, KS
24Mayo Clinic, Rochester, MN
25Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
26Virginia Commonwealth Univ/Massey Cancer Center, Richmond, VA
27Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH
28UCSD Moores Cancer Center, Carlsbad, CA
29Roswell Park Comprehensive Cancer Center, Buffalo, NY
30Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC
31Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD
32National Cancer Institute, National Institutes of Health, Bethesda, MD
33Duke University Cancer Institute, Durham, NC
34Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA
35Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Highland Park, IL
36Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston Salem, NC

Introduction: Based on a donor versus no-donor analysis, UKALLXII/E2993 showed a survival benefit for adults with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR1) compared to consolidation/maintenance chemotherapy alone. The follow-up phase 3 E1910 trial (NCT02003222) randomized BCR::ABL1-negative B-lineage ALL patients (pts) aged 30-70 years in measurable residual disease (MRD)-negative CR1 after intensification to conventional chemotherapy (CC) +/- blinatumomab (blin) and demonstrated significantly improved overall survival (OS) with blin (Litzow, NEJM 2024). The current exploratory subgroup analysis evaluates outcomes of MRD-negative pts randomized on E1910 who underwent alloHCT on trial.

Methods: Among pts enrolled on E1910, pts in MRD-negative CR1 by 6-color flow cytometry after intensification who were randomized to CC +/- blin and subsequently underwent alloHCT were identified. We compared baseline characteristics, MRD status post induction, relapse-free survival (RFS) and OS using the Kaplan-Meier method and the two-sided log-rank test and Cox model. A multivariable analysis was performed with alloHCT included as a time-varying covariate as well as a landmark analysis comparing the outcome of pts with unfavorable risk on the CC + blin arm who underwent alloHCT versus those who did not.

Results: Of 224 MRD-negative randomized pts, 44 underwent alloHCT on trial: 22 in each arm. The median time from randomization to transplant was 3.2 months (mos). The median follow-up from initial registration was 57.8 mos.

Baseline demographics including age (median 55 years), gender (53% male), race (89% white) and ethnicity (89% non-Hispanic/Latino) were equally distributed. Compared to CC + blin, the median peripheral blood white cell (WBC) count and blast percentage at diagnosis were higher in the CC arm at 6,640 vs 3,740/uL and 55 vs 9%, respectively, while median marrow blast percentage and overall unfavorable risk as defined in E1910 (55% vs 64%) were similar. Of the 44 MRD-negative pts who proceeded to alloHCT on study, 77% in the CC arm and 64% in the CC+ blin arm were MRD-negative after induction. Myeloablative conditioning was given to the majority of pts (68% CC arm and 73% CC+blin arm) and the most common graft versus host disease prophylaxis was tacrolimus-based on both arms.

Among the 44 pts who underwent alloHCT, the observed hazard ratio (HR) comparing relative risk of death between pts randomized to CC+blin or CC only was 0.59 (95% CI: 0.12-2.11) with a 3-year OS rate of 82% versus 71% and the HR comparing relative risk of relapse/death was 0.52 (CI: 0.15-1.79) with a 3-year RFS rate of 82% versus 67%. For patients with unfavorable risk, 3-year OS and 3-year RFS in each treatment arm were both 71% versus 65%.

Among 50 pts with unfavorable risk in MRD-negative CR after intensification who were randomized to CC + blin, a landmark analysis performed at 5 mos post randomization showed 3-year OS and RFS rates of 71% versus 90% and 71% versus 86% between the 14 pts who underwent alloHCT and those who did not, respectively.

Receipt of alloHCT was a time-varying covariate in a multivariable analysis with gender, WBC count, platelets, hemoglobin, peripheral blood blasts, bone marrow blasts, performance status, and combined molecular risk category. Age, CD20 status, rituximab use, and intention to receive alloHCT were used as stratification factors. In the entire cohort of MRD-negative pts who were randomized, there was a significant association between improved OS and the receipt of CC+blin vs CC alone (HR 0.46, 95% CI: 0.26 - 0.82; p=0.009), better performance status of 0-1 vs ≥2 and favorable vs unfavorable risk ALL. In contrast, the receipt of alloHCT had no significant effect on OS (HR 1.00, 95% CI: 0.49 – 2.01).

Conclusions: Within the constraints of small numbers, this exploratory subgroup analysis demonstrates that in pts with newly diagnosed BCR::ABL1-negative B-ALL treated on E1910 who achieved MRD-negativity after intensification, alloHCT outcomes did not appear to be different with or without blin in consolidation. In a multivariate analysis of all MRD-negative pts, receipt of blin but not alloHCT was associated with improved OS. Further investigation is warranted to characterize the relative benefit of blinatumomab in pts receiving alloHCT in frontline consolidation.

Disclosures: Liedtke: BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomea: Research Funding; Allogene: Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum/Alexion: Research Funding; Gilead: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees; Nexcella: Membership on an entity's Board of Directors or advisory committees; Seagen: Research Funding. Litzow: Abbvie: Research Funding; Amgen: Research Funding, Speakers Bureau; Actinium: Research Funding; Astellas: Research Funding; Pluristem: Research Funding; Sanofi: Research Funding; Beigene: Speakers Bureau; Biosight: Other: Data Safety Monitoring Committee. Lazarus: Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Geron: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; BioSight: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; GlycoMimetics: Consultancy, Honoraria; CSL Behring: Consultancy; Pluristem Therapeutics, Inc: Consultancy, Honoraria; Partner Therapeutics: Consultancy, Current holder of stock options in a privately-held company; Actinium Pharmaceuticals, Inc: Consultancy, Honoraria. Rowe: BioSight: Consultancy. Bergeron: Palladin: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Daichi Sanho: Consultancy; Abbvie: Honoraria; Astellas: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Taiho: Membership on an entity's Board of Directors or advisory committees. Wood: Cellnomics LLC: Current equity holder in private company; Amgen: Consultancy. Pratz: AbbVie: Consultancy, Research Funding; Kura Oncology: Research Funding; Immunogen: Consultancy. Dinner: Kite: Consultancy; Rigel: Consultancy; Pfizer: Consultancy. Atallah: Novartis Pharmaceuticals Corporation: Honoraria. Jeyakumar: Jazz Pharma: Research Funding; Pfizer: Research Funding. Lin: Jazz Pharmaceuticals; Servier: Consultancy; Aptevo; Bio-Path Holdings; Ciclomed; Cleave; Jazz; Jazz Pharmaceuticals; Leukemia & Lymphoma Society; Kura Oncology; Trovagene: Research Funding. DeAngelo: AbbVie, Blueprint, GlycoMimetics, Novartis: Research Funding; Amgen, Autolus, Blueprint, Gilead, Incyte, Jazz, Novartis, Pfizer, Servier, Takeda: Consultancy; Mt Sinai MPN Consortium: Other: Mt Sinai MPN Consortium; Dana-Farber Cancer Institute: Current Employment; Daiichi-Sankyo, Fibrogen: Other: DSMB. Advani: Immunogen: Research Funding; Wiley: Honoraria; Incyte: Research Funding; MD Education: Honoraria; Web MD: Honoraria; Emmes: Honoraria; OBI: Research Funding; MJH Life: Honoraria; BEAM: Other: Research support, Research Funding; Glycomimetics: Research Funding; American Society of Hematology: Honoraria; Springer: Honoraria; Amgen: Research Funding; Wolters Kluwer: Honoraria; Pfizer: Other: Manuscript help, Research Funding; PER: Honoraria; Kite: Consultancy, Research Funding; Seattle Genetics: Research Funding; Macrogenics: Research Funding; Servier: Research Funding; Kura: Research Funding; Novartis: Consultancy. Tzachanis: BMS: Consultancy. Vachhani: Abbvie: Consultancy; Amgen: Consultancy; Blueprint Medicines Corporation: Consultancy; Cogent Therapeutics LLC: Consultancy; Daiichi Sankyo Company: Consultancy; Genentech: Consultancy; GlaxoAmithKline, LLC.: Consultancy; Incyte Corporation: Consultancy; Karyopharm Therapeutics: Consultancy; Lava therapeutics: Consultancy; MorphoSys: Consultancy; Novartis Pharma: Consultancy; Pfizer: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Sobi, Inc: Consultancy; Stemline Therapeutics Inc: Consultancy. Sharon: Mallinckrodt Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; D.E. Shaw Research: Consultancy. Erba: Daiichi Sankyo: Honoraria. Stone: Aptevo: Consultancy; Redona therapeutics: Consultancy; Janssen: Other: Research funding to my institution; Ligand Pharma: Consultancy; Novartis: Other: Research funding to my institution; Kura Oncology: Consultancy; Hermavant: Consultancy; Syntrix: Other: DSMB; Jazz: Consultancy; AMGEN: Consultancy; Syndax: Other: Research funding to my institution; Lava Therapeutics: Consultancy; Rigel: Consultancy; AbbVie: Consultancy, Other: Research funding to my institution; Glycomimetrics: Consultancy; Epizyme: Consultancy, Other: DSMB; ENSEM: Consultancy; AvenCell: Consultancy; CTI Biopharma: Consultancy; Cellarity: Consultancy; Glaxosmithkline: Consultancy; Bristol Meyers Squibb: Consultancy; Daiichi Sankyo: Consultancy; Curis Oncology: Consultancy; BerGenBio: Consultancy; Takeda: Other: DSMB. Luger: AbbVie: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Marker Therapeutics: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy. Tallman: Adjudication Committee Foghorn Therapeutics FG286: Membership on an entity's Board of Directors or advisory committees; Moleculin: Membership on an entity's Board of Directors or advisory committees; UpToDate: Other: Royalties.

*signifies non-member of ASH