Page 65 - 2021_07-Haematologica-web

Final results of the GIMEMA LAL1509 for Ph+ ALL
A
Figure 5. Survival stratified according to molecular response at the end of induction. (A) Disease-free survival (DFS) and (B) overall survival (OS). CI: Confidence Interval; CHR: complete hematologic remission; yrs: years.
B
mostly in an era in which a plethora of novel compounds are available.
Even if the numbers are small and protocol violations rep- resent a major limit, the DFS of the few cases in persistent CHR and CMR seems to be better than that of patients who did not achieve CMR. This suggest that some patients, regardless of their age, may be spared systemic chemotherapy and transplant procedure. However, the applicability of this strategy must be carefully evaluated and possibly refined by additional genetic information. Indeed, this chemo/transplant-sparing strategy is addressed in an ancillary study (clinicaltrials gov. Identifier: NCT03318770) to our recently published paper on adult Ph+ ALL patients of all ages treated in induction with dasa- tinib and consolidated with the bispecific monoclonal anti- body blinatumomab.31
Regarding patients in CHR who did not achieve CMR, 35 received chemotherapy consolidation with clofarabine- cyclophosphamide: overall, this treatment was capable of
inducing CMR in 12 cases (34.3%), thus indicating its effec- tiveness and in some cases a valuable bridge to transplant. Furthermore, this strategy was safe, since only 18 SAE were recorded in ten patients. Similarly, allo-SCT proved effec- tive in inducing MRD negativity in 32% of the patients.
Seventeen hematologic relapses (comprising two extramedullary) and 11 deaths in CHR were recorded. We observed a 5-year DFS of 47.2% and a 5-year OS 56.3%, making the outcome of Ph+ ALL patients almost compara- ble to that of Ph- ALL cases. These results represent a slight improvement compared to our previous trial - GIMEMA LAL090417 - based on a chemotherapy-free imatinib admin- istration in induction, followed by consolidation and allo- SCT, in which the 5-year DFS and OS were 45.8% and 48.8%, respectively. The finding that DFS was not signifi- cantly superior might be related to the well-established fact that dasatinib, even though more effective in rapidly eradi- cating a leukemic clone, is not capable of overcoming the occurrence of TKI-resistant mutations, particularly the
haematologica | 2021; 106(7)
1835