Real-World Experience of Blinatumomab for 8 Years Regarding Predictive Factors Including Lymphocyte Kinetics for Response and Survival Outcome in Adult Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia

Background: Blinatumomab became available in Korea since 2016 and has proved its efficiency for remission and safe bridging role to allo-HCT in patients with R/R BCP-ALL. This T-cell engager system has changed the paradigm of ALL treatment in terms of safe chemotherapy-free approach and need for understanding T-cell immunology.

Aim: Here, we report our long-term experience of blinatumomab regarding well-known traditional factors and lymphocyte kinetics during blinatumomab treatment.

Methods: We analyzed 152 adult patients (median age 59.5 years, range 18-79) with R/R BCP-ALL treated with blinatumomab between 2016 and 2023 (110 Ph-negative, 42 Ph-positive). Ph-negative BCP-ALL could be treated with blinatumomab from first line salvage while Ph-positive BCP-ALL after Dasatinib failure, thus at least from second line salvage. The standard protocol consisted of pre-phase dexamethasone, first cycle blinatumomab 28 days (9mcg during initial 7 days followed by 28mcg for 21 days) was followed by 2-week resting period and second or more cycle of 28mcg blinatumomab for 28 days. For post-remission therapy, allo-HCT was conducted as early as possible.

Results: After first cycle, CR was achieved in 98 (64.5%) and best response was in 104 (68.4%) patients after median 2 cycles, and 74 responders (48.7%) subsequently proceeded to allo-HCT. After median follow-up of 45.2 months, 4-year OS and CIR was 25.7% and 61.0% in entire cohort, and 37.0% and 47.9% after allo-HCT. We observed higher relapse rate with short CR duration, PB blast prior to blinatumomab, and later-line salvage were related with poor response to blinatumomab and old age and early relapse for poor OS even after allo-HCT. Regarding absolute lymphocyte count (ALC), ALC at first day of blinatumomab was not significantly associated with CR rate (OR=1.00, P=0.0523), OS (ALC≥500: 21.8% vs. ALC<500 36.6; P=0.160), as well as CIR (ALC≥500: 50.2% vs. ALC<500 55.7; P=0.819). However, we observed ALC decrement>2000/mcL at 2-weeks after blinatumomab was predictive for poor response (OR 2.88, P=0.011), and that ALC<250/mcL and decrement>2000/mcL at 2-weeks after blinatumomab was associated with poor survival (Figure).

Conclusions: Our data shows that blinatumomab can be effective even in patients with low ALC at first day of blinatumomab, and that lesser decrease in ALC predicts higher CR in adult patients with R/R ALL.

Park:ImpriMed, Inc.: Consultancy, Current holder of stock options in a privately-held company. Kim:AbbVie, AIMS Bioscience, AML-Hub, Astellas, BMS & Celgene, Boryung Pharm Co., Daiichi Sankyo, Janssen, Handok, LG Chem, Novartis, Pfizer, SL VaxiGen, VigenCell, Aston Bioscience, Ingenium, Amgen, Sanofi Genzyme, Takeda, Meiji Pharm Co. and GreenCross Phar: Consultancy; AbbVie, Astellas, BMS, Handok, Novartis, AML-Hub, Jazz Pharmaceuticals and Takeda: Honoraria, Speakers Bureau; BL&H: Research Funding; BMS & Celgene, Novartis, APLC, AbbVie, Astellas, Janssen, Handok, Pfizer, Sanofi Genzyme, AML-Hub, Daiichi Sankyo and APBMT: Membership on an entity's Board of Directors or advisory committees.