The PETHEMA Spanish group treats patients with high-risk Philadelphia chromosome-negative
ALL, aged 18 to 55 years, based on the MRD clearance as assessed by flow cytometry at a
centralised evaluation centre. Patients with MRD < 0.1% (< 1×10-3) after induction and <
0.01% (< 1×10-4) after early consolidation are assigned to receive chemotherapy (late
consolidation and maintenance).
Early consolidation chemotherapy consists of three cycles including high doses of MTX, ARA-C
and ASP, together with vincristine and dexamethasone. The same therapy is repeated in the
late consolidation period if MRD after early consolidation is < 0.01% (< 1×10-4). Maintenance
therapy is then administered for up to 2 years from the CR date. These patients do not
receive allo-HSCT if they maintain adequate MRD clearance.
Despite having adequate MRD clearance, a proportion of patients (around 25%) experience
relapse, which makes other approaches necessary to try to decrease the relapse rate.
Intensifying currently existing chemotherapy regimens is not likely to increase the cure rate
and would likely significantly increase toxicity. The use of targeted immunotherapeutic
agents such as blinatumomab, which has demonstrated efficacy and safety in patients with R/R
ALL and in patients with ALL and MRD+, seems to be a promising option [30-33].
Therefore, it would be interesting to assess the potential efficacy of using blinatumomab in
CR patients to reduce the MRD more frequently and more intensely during the early and late
consolidation period. Our hypothesis is that blinatumomab will further reduce the level of
MRD and this could lead to a decrease in the relapse rate in these patients.
This trial will replace the third early consolidation cycle with a cycle of blinatumomab, and
the same will be done in the late consolidation period. We hope that this strategy will
increase the extent of the MRD response and prevent relapses.
Moreover, and as a secondary objective, we will investigate the safety of blinatumomab
administration after the administration of high-dose chemotherapy including MTX, ARA-C and
ASP