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S. Chiaretti et al.
A
Figure 4. Survival estimates.
B
Discussion
We herein reported the final results of the GIMEMA LAL1509 trial for adult Ph+ ALL patients. This protocol was based on a total therapy strategy that comprised a chemotherapy-free induction based on dasatinib, plus steroids and CNS prophylaxis, followed by a post-remis- sion treatment tailored according the molecular response. Patients in sustained CMR continued with dasatinib, while patients in CHR who did not achieve CMR under- went chemotherapy consolidation with clofarabine- cyclophosphamide plus an allo-SCT for eligible patients. The protocol was designed to evaluate the efficacy of a post-induction treatment modulated on the basis of the depth of molecular response and represents, so far, the first protocol to investigate the possibility of chemother- apy-free consolidation in adult patients (18-60 years) in CMR.
This study confirms the effectiveness of chemothera- py-free induction with dasatinib plus steroids in Ph+ ALL adult patients in inducing a rapid clearance of a neoplastic clone16 and also confirms that this strategy is less toxic than combinational strategies,19,27-30 since no deaths during
induction were recorded, as already reported in previous GIMEMA trials for Ph+ ALL.7,16,17
Of the 60 eligible patients, 97% reached CHR at the end of the induction with two patients in CHR at day +57, both harboring the p210 fusion protein, who relapsed between day +57 and +85 of the induction phase. At the end of the induction (day +85), CMR - confirmed by a second BM aspirate after 15 days - was achieved in 11 cases (18.3%). Seven of these 11 patients continued treatment with dasa- tinib: four patients are still alive and disease-free (one under- went allo-SCT while in CMR), one patient underwent allo- SCT and died of transplant-related complications, one patient experienced a hematologic relapse and one patient suffered molecular recurrence; the latter two cases both had an IKZF1-plus phenotype. The remaining four CMR patients were rapidly switched to different therapeutic options, two due to a molecular increase and two due to protocol violations (i.e., transplant allocation and non-com- pliance). With regards to the two cases with molecular recurrence, a strict MRD monitoring prevented an overt hematologic relapse (resulting in a benefit for patients) and may thus represent a bias of the study; nevertheless, it fur- ther highlights the importance of molecular monitoring,
(A) Disease-free survival (DFS) and (B) overall survival (OS). CI: Confidence Interval; CHR: complete hematologic remis- sion; yrs: years.
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haematologica | 2021; 106(7)