Frail/unfit patients
Therapeutic options for frail or unfit patients include the combination of dasatinib and prednisone, which was associated in one study with a 93% complete hematologic remission rate by day 22, and at 20 months with a 69.2% overall survival rate, and 51.1% disease-free survival rate.(Blood. 2011;118[25]:6521-8).
In this study MRD correlated with disease-free survival, but 23 of 53 patients experienced relapse, and 12 patients with relapsed disease had the T3151 mutation. Ponatinib would be a second-line option for this latter group of patients, Dr. Advani said.
A study reported at the 2017 ASH annual meeting looked at the combination of ponatinib with steroids in patients either 60 and older or younger unfit patients with Ph+ALL.
The primary endpoint of complete hematological response at 24 weeks in at least 75% of patients was reached early, with 40 of 42 patients (95.2%) having a complete hematologic response after 1 course of therapy (6 weeks). The CMR rate at 24 weeks was 61%, and 1-year overall survival was 87.5%.
There were 13 serious adverse events related to ponatinib, however, including one death, and one patient who experienced a relapse was found to have the T315L ponatinib-resistance mutation. (Blood 2017 Dec. 7;130[Suppl. 1]:99).
“I think a few things with ponatinib and steroids that we still don’t know are the long-term follow-up results of this as a single agent in combination with steroids, and second, in this elderly population, if you look, patients are dropping out due to adverse events and toxicities,” she said.
TKIs plus antibodies
The S1318 trial conducted by the SWOG cancer research network contains both a Ph+ALL and a Ph-negative ALL cohort. In this trial, patients with Ph+ALL receive dasatinib and steroids as induction, then go on to receive blinatumomab (Blincyto) with dasatinib for three cycles, followed by maintenance therapy with dasitinib and prednisone.
A trial currently in the planning stages, EA9181, will compare in a randomized fashion induction regimens with either dasatinib or ponatinib at the investigator’s discretion with steroids and either blinatumomab or chemotherapy.
No funding source was reported for the presentation. Dr. Advani disclosed steering committee activities, honoraria/consulting, and research funding from multiple companies.