Page 75 - Haematologica Vol. 107 - September 2022

ARTICLE - High tumor burden and response to blinatumomab A. Cabannes-Hamy et al.
17-74). At diagnosis, the median white blood cell count (WBC) was 8.1x109/L (range, 1.0-731.0). The karyotype showed a Philadelphia chromosome in three patients (9%), a KMT2A (formerly MLL) rearrangement in three patients (9%) and a low hypodiploidy/near triploidy in three pa- tients (9%). An intragenic deletion of IKZF1 gene was found in five of 19 screened patients (26%). Two patients had previously received an HSCT. Interim chemotherapy was given while waiting for treatment approval and delivery ac- cording to local investigator choice. Before blinatumomab infusion, only three of 32 (9%) patients had MRD <0.01%, and the majority (18/32, 56%) had MRD >0.1%.
The median age of the relapse cohort was 49 years (range, 16-74). Among these 38 patients, 11 had a Ph+ ALL (29%), two had a KMT2A rearrangement (6%), and three had a t(1;19) translocation. An IKZF1 intragenic deletion was found in five of 21 evaluated patients (24%). Around two thirds of these patients received blinatumomab in first re- lapse (63%), and 15 of 38 (39%) had previously received an allogeneic HSCT. Due to local investigator decisions, pa- tients could have received chemotherapy before blinatu- momab. Among these 38 patients, 15 (39%) were in second or greater remission (CR2+) at the time of blinatumomab. Among these patients in CR2+, three of 11 (27%) had MRD of <0.01%, while the majority (7/11, 64%) had MRD of >0.1%.
Efficacy of blinatumomab in the minimal residual disease-positive cohort
Patients from the MRD+ cohort received a median of one cycle of blinatumomab (range, 1-2). Blinatumomab was started at the dose of 9 mg/day in ten of 24 patients (29%)
and 28 mg/day in the remainders (71%, 1 missing data). Among the 33 patients with available data, 23 received a premedi- cation with dexamethasone (range, 20-40 mg total dose). Upon blinatumomab, a complete MRD response was ob- served in 31 of 35 patients (89%). Among the 35 patients, 23 (66%) proceeded to allogeneic HSCT in continuous CR. The median follow-up of this cohort was 3.6 years. A re- lapse was observed in six patients. Both the median RFS and OS were not reached (Table 2; Figure 2A and B). In this cohort, the 3-year RFS was 65% and the 3-year OS was 68%. When patients were censored at the time of HSCT performed in continuous CR after blinatumomab, the 3- year RFS was 71% and the 3-year OS was 77% (Online Sup- plementary Figure S1A and B).
Efficacy of blinatumomab in the relapse cohort
Patients from the relapse cohort received a median of one blinatumomab cycle (range, 1-5). CR was reached in 26 of 38 patients (68%, Table 2). Eleven of the 23 patients not in CR at the time of blinatumomab achieved CR (48%). Among the 26 patients in CR after blinatumomab, a com- plete MRD response was observed in 21 of 25 patients (84%) with no difference between patients in previous CR (12/14, 86%) or not (9/11, 82%, P=0.99). Twelve of 26 CR patients (46%) were bridged to allogeneic HSCT in con- tinuous CR (Table 2). The median follow-up of this cohort was 3.3 years. The median RFS and OS were respectively 14.6 and 10.3 months (Table 2; Figure 3A and B). At 3 years, the RFS was 37% and OS was 35%. When follow-up was censored at transplant time, 3-year RFS was 38% and 3- year OS was 32% (Online Supplementary Figure 2A and B).
Figure 1. Flow-chart of the study population. CR1: first complete remission; CR2+: patients in second or greater complete remission; MRD: minimal residual disease; R/R: relapsed/ refractory; ALL: acute lymphoblastic leukemia.
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