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:Actinium Pharmaceuticals, Inc: Consultancy; Partner Therapeutics: Consultancy, Current holder of stock options in a privately-held company; Pluristem Therapeutics, Inc: Consultancy; CSL Behring: Consultancy; GlycoMimetics: Consultancy; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; BioSight: Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Seattle Genetics: Speakers Bureau; Geron: Speakers Bureau; Pfizer: Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau. 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:PER: Honoraria; OBI: Research Funding; Incyte: Research Funding; American Society of Hematology: Honoraria; Springer: Honoraria; Glycomimetics: Research Funding; Servier: Research Funding; Macrogenics: Research Funding; Wiley: Honoraria; Amgen: Research Funding; Immunogen: Research Funding; MD Education: Honoraria; Pfizer: Other: Manuscript help, Research Funding; Seattle Genetics: Research Funding; Kura: Research Funding; BEAM: Other: Research support, Research Funding; Novartis: Consultancy; Emmes: Honoraria; Web MD: Honoraria; Wolters Kluwer: Honoraria; Kite: Consultancy, Research Funding; MJH Life: Honoraria. 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:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Marker Therapeutics: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees. 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.

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2024
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