Page 78 - Haematologica Vol. 107 - September 2022

ARTICLE - High tumor burden and response to blinatumomab A. Cabannes-Hamy et al. AB
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Figure 4. Impact of pre-blinatumomab tumor burden on outcome. (A) Relapse-free surviavl (RFS) and (B) overall survival (OS) in minimal residual disease-postive (MRD+) patients according to pre-blinatumomab MRD. (C) RFS and (D) OS in relapsed patients according to pre-blinatumomab complete response (CR).
larger prospective trials.9,10 In addition, we report here that the tumor load before blinatumomab initiation has a strong impact on patient outcome whatever the disease status. This parameter should thus be considered to de- sign future salvage strategies.
Among the patients exposed to blinatumomab in first CR and with persistent MRD, 89% achieved a complete MRD response. The median RFS and OS were not reached with a 3-year RFS and OS of 65% and 68% respectively. This ob- servation is in line with the BLAST trial for adults with MRD+ ALL that reported a 80% complete MRD response rate after one course of blinatumomab.10 In the BLAST subgroup analysis, patients in CR1 achieved a complete MRD re- sponse in 83% of cases after the first course of blinatumo- mab and the median RFS was not reached for patients who achieved complete MRD response. In the present cohort, censoring outcome analyses at the time of HSCT did not modify estimates, which should encourage to further in- vestigate the role of transplantation in MRD+ patients after
blinatumomab therapy. Of note, heterogeneity in the tech- niques used to assess MRD response may be considered as a limitation of the present study.
Whereas the prognostic impact of MRD response after bli- natumomab is well described,10 the role of pre-blinatumo- mab MRD remains poorly explored. In the BLAST study, which included patients with MRD ≥0.1%, a complete MRD response was achieved in only six of nine (67%) patients with an MRD level ≥10%.10 In the present MRD+ cohort, pre-blinatumomab MRD levels had a strong impact on pa- tient outcome and inversely correlated with RFS and OS. In previous pediatric and adult ALL studies, the same im- pact was observed for pre-transplant MRD identified as a post-transplant relapse predictor.16,17 In both pre-blinatu- momab or pre-transplant settings, it remains unclear whether a high MRD level is just a marker of higher intrin- sic resistance of the disease, or also contributes to unfa- vorable target-to-effector ratios that disable effector cells. In MRD+ patients, there are limited options in terms of
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