Session: Late-Breaking Abstracts Session
Hematology Disease Topics & Pathways:
antibodies, Biological, ALL, Leukemia, Diseases, Therapies, Pediatric, Young Adult, immunotherapy, Study Population, Lymphoid Malignancies, Clinically relevant
A total of 208 HR/IR patients were randomized (Arm A: 103, Arm B: 105). Baseline characteristics were comparable between arms (Table 1). With median follow up of 1.4 years, the intent-to-treat (ITT) 2-year DFS (% ± standard error) was 41.0 ± 6.2% for Arm A vs. 59.3 ± 5.4% for Arm B (p=0.05, 1-sided per pre-specified statistical plan)(Figure 1A). The ITT 2-year OS was 59.2 ± 6.0% for Arm A vs. 79.4 ± 4.5% for Arm B (p=0.005, 1-sided)(Figure 1B). Among patients with detectable MRD (≥0.01%) at the completion of Block 1 chemotherapy, the proportion that achieved undetectable MRD (<0.01%) after Block 2 (Arm A) vs. Blina cycle 1 (Arm B) was 21% vs. 79% (p<0.0001)(Table 2). The rates of MRD response were similar with Block 3 or Blina cycle 2 (Table 2). Post-induction toxic deaths occurred in 4 patients on Arm A (all infections) vs. none on Arm B (p=0.05). Relative rates of CTCAEv4 grade ≥3 febrile neutropenia, infections, sepsis and mucositis were strikingly higher for Block 2/3 (Arm A) vs. Blina cycle 1/2 (Arm B): 44%/46% vs. 4%/0%, 41%/61% vs. 10%/11%, 14%/21% vs. 1%/2%, and 25%/7% vs. 0/1% respectively (p<0.001 for all comparisons except mucositis for Block 3 vs. Blina cycle 2, p=0.16). For Arm B, the rate of selected blinatumomab-related AEs in cycle 1/2 were: Cytokine release syndrome (CRS) 22%/1% (grade ≥3 1%/0%); seizure 4%/0% (1%/0%); other neurotoxicity (e.g., cognitive disturbance, tremor, ataxia, dysarthria) 14%/11% (2%/2%). All blinatumomab-related AEs fully resolved. The rate of patients successfully proceeding from randomization to HSCT (data cut-off 9/30/19) was strikingly different between arms. On Arm A, only 45% (44 of 98 who received randomized therapy) proceeded to HSCT. On Arm B, 73% (75 of 103 who received randomized therapy) proceeded to HSCT (p<0.0001).
In conclusion, for children and AYA patients with HR/IR first relapse of B-ALL, blinatumomab is superior to standard chemotherapy as post-reinduction consolidation prior to HSCT, resulting in fewer and less severe toxicities, higher rates of MRD response, greater likelihood of proceeding to HSCT and improved disease-free and overall survival. Patients remain in follow up, and prospectively defined analyses of longer-term outcomes will be forthcoming.
Disclosures: Brown: Novartis: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees. Borowitz: Beckman Coulter: Honoraria. Raetz: Pfizer: Research Funding. Zugmaier: Amgen: Employment, Other: holds stock, Patents & Royalties: & other intellectual property. Gore: Amgen: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Novartis: Consultancy, Other: Service on Data Safety Monitoring Committee; travel, accommodations, expenses; Roche/Genentech: Consultancy, Honoraria, Other: travel expenses; Anchiano: Equity Ownership, Other: spouse employment and company leadership; Blueprint Medicines: Equity Ownership; Celgene: Equity Ownership, Other: DSMC member; Clovis: Equity Ownership; Mirati: Equity Ownership; Sanofi Paris: Equity Ownership. Pulsipher: Medac: Honoraria; Miltenyi: Research Funding; Bellicum: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Other: Education for employees; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Lecture. Hunger: Amgen: Consultancy, Equity Ownership; Bristol Myers Squibb: Consultancy; Jazz: Honoraria; Novartis: Consultancy. Loh: Medisix Therapeutics, Inc.: Membership on an entity's Board of Directors or advisory committees.
OffLabel Disclosure: Investigational use of blinatumomab