Interim Results of Russian Acute Lymphoblastic Leukemia (RALL-2016) Study with Centralized MRD-Monitoring and Randomization for Autologous HSCT with Non-Myeloablative Conditioning in Adult Ph-Negative ALL Patients

Introduction. MRD-tailored therapy based on pediatric-inspired intensification is a back-bone of the majority of the European study groups in adult ALL. Taking in consideration the major pitfalls of the first Russian acute lymphoblastic leukemia study group trial RALL-2009 (NCT01193933) - high CR death rate, early CNS relapses in T-ALL, selection bias in auto-HSCT vs chemotherapy comparison, absence of MRD monitoring - a new RALL-2016 protocol (NCT03462095) was introduced based on the same principles as the first one - non-intensive but non-interruptive approach with low numbers of allo-HSCT, but with further deintensification of consolidation phase, centralized MRD-monitoring and randomization for autologous HSCT with non-myeloablative conditioning (CEAM). AIM. To analyze the 2,5 years efficacy and to determine significance of MRD status after induction in the new Russian ongoing prospective multicenter study RALL-2016. Materials and patients. RALL-2016 was based on the previous RALL-2009 protocol , but one day high-dose MTX and high-dose ARA-C blocks were eliminated and substituted by 2 months of non-interruptive therapy, L-asparaginase was scheduled for 1 year of treatment instead of 2,5 y, 15 intrathecal injections were increased up to 21 mostly while consolidation phase, CR T-ALL patients were brought to randomization after the informed consent: auto-HSCT vs no auto-HSCT, - with the similar further maintenance. All primary bone samples are collected and tested for cytogenetics and molecular markers, all included patients are monitored by flow cytometry by aberrant immunophenotype in a centralized lab. Results and discussion. From Dec 2016 till Jul 2019 148 Ph-negative ALL pts from 10 centers were included: median age 33 y (18-54) (BCP-ALL-80 (54%) pts, T-ALL- 64 (44%), biphenotypic- 4 (2%)). CR was achieved in 84% pts. The induction death before CR was 8% (n=12), refractory ALL was registered in 12 pts (8%). Death in CR occurred in 4%. After CR achievement 52 T-ALL patients were randomized either to chemotherapy (n=25) or to autoHSCT(n= 27). 15 of 27 T-ALL pts were transplanted at a median time of 6 months from CR (1 of 27 received alloHSCT - Neimegen Syndrom, 2 of 27 died in CR before HSCT, one pt refused the autotransplant ). OS and DFS at 2-years constituted 70,7% and 80%. 2-y OS was 65,8% for BCP-ALL, 80% for T-ALL and 66,7% for MPAL (p=0,5). 2-y DFS was 78,7% for BCP-ALL, 83,4% for T-ALL and 100% for MPAL (p=0,88). AlloHSCT in 1st CR have receive