Page 80 - Haematologica Vol. 107 - September 2022

ARTICLE - High tumor burden and response to blinatumomab A. Cabannes-Hamy et al.
BCP-ALL aged up to 60 years old, a second CR is expected in about 50% of cases.19,20 The most important factor as- sociated with the chance to reach a second CR is CR1 dur- ation. In late relapses with CR1 duration >18 months, reported CR2 rates ranged from 58% to 68%.19,20 In the TOWER study for adult R/R B-ALL, patients in first relapse could be included if CR1 duration was shorter than 12 months or after HSCT. Patients who received blinatumo- mab as first salvage, most of them being in first relapse, had an overall response rate of 51%, a CR rate of 44%, and a median survival of 11.1 months.25 Altogether, these ob- servations encourage to try to reach a second CR with chemotherapy-based regimen before exposing patients to blinatumomab consolidation, particularly in younger pa- tients with late relapse.
The place of blinatumomab combined to chemotherapy in frontline or R/R B-ALL is being intensively explored. The MD Anderson Cancer Center reported on the combination of Hyper-CVAD-derived regimen, inotuzumab ozogamicin, and blinatumomab in elderly patients with frontline B-ALL or in younger adult patients with R/R diseases.26,27 More recently, phase II assessing the role of frontline consoli- dation with blinatumomab in adult B-ALL were reported by the GIMEMA group and by our group.28,29
In conclusion, this real-world study confirms the benefit of blinatumomab in adult patients with either primary resis- tant BCP-ALL or at relapse and suggests an impact of pre- blinatumomab tumor burden on patient outcome. Many limitations have been highlighted throughout the dis- cussion, mostly related to the retrospective nature of the study, to the non-controlled nature of the comparisons, and more specifically to the selection of patients in second CR after chemotherapy compared to patients exposed to blinatumomab in overt relapse. It is however unlikely that
References
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a randomized study will address this important question. In early resistant disease with MRD+, our observation sup- ports the design of post-blinatumomab strategies includ- ing transplantation. In relapsed patients, especially in first salvage, our results along with recent published observa- tions support to discuss the best timing schedule of bli- natumomab, after salvage chemotherapy rather than in overt relapse. The underlying mechanisms that contribute to an increased risk of failure in patients with high tumor burden remain to be explored.
Disclosures
ACH declare no conflicts of interest. NB was employed on advisory boards and received research subsidies from AMGEN.
Contributions
ACH, NB and VL designed, performed and coordinated the research. ACH and VL collected data. NB performed statis- tical analyses and produced the figures. ACH and NB ana- lyzed, interpreted the data and wrote the manuscript. EB, TL, FH, PC, MH, MEB, TC, MB, SN, SB, MA, CP, ED, EC, HD in- cluded patients, contributed data and commented on the manuscript
Acknowledgements
We thank all data managers for their help in collecting and updating data.
Funding
This study was supported by Amgen.
Data-sharing statement
For original data, please contact nicolas.boissel@aphp.fr
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