The patients with the highest levels of inhibition had the greatest likelihood of RFS, whereas RFS in those with suboptimal pFLT3 inhibition was similar to that seen in the SOC-only arm, Dr. Maziarz said. Two patients in the midostaurin group who relapsed did so after 12 months – when midostaurin had been discontinued, he noted.
“Our conclusion is that maintenance midostaurin may contribute to a reduction in relapse risk at 18 months post transplant ... and can be safely administered in the posttransplant setting,” Dr. Maziarz said. “pFLT3 inhibition to less than 70% of baseline, at least in this study, was associated with improved relapse-free survival and overall survival, and it was achieved in more than 50% of patients on the midostaurin.”
It is likely that a more definitive answer will be provided by the Blood and Marrow Transplant Clinical Trials Network Protocol 1506, a large, multinational, placebo-controlled trial now recruiting to look at this question of whether maintenance therapy in the posttransplant setting will improve outcomes.
However, it is important to note that no patient in the RADIUS trial received pretransplant midostaurin, as RADIUS was conducted at the same time as the RATIFY trial.
“Patients today who will go to transplant with FLT3-ITD, the vast majority will have been treated during induction ... and we may have a totally different biology going forward,” he said.
Dr. Maziarz reported financial relationships with Incyte, Novartis, Celgene/Juno, Kite/Gilead, Juno Therapeutics, Kite Therapeutics, and Athersys.