45 y/o F with AML, inv16, with NGS +FLT3 TKD and +NRAS mutations, and biopsy-proven leukemia cutis (right leg). Received 7+3 (without midostaurin as the rapid AML panel was initially negative, but final myeloid NGS panel showed the FLT3 mutation). I consulted with several transplanters and the consensus has been to hold off on transplant in CR1 if she is MRD negative. She is now s/p HiDAC consolidation with midostaurin, although she only took the midostaurin for a few days each cycle and it was held during several admissions for fever/bacteremia. Post-consolidation bone marrow biopsy is negative, and MRD assessment is also negative for inv16 and FLT3. Repeat skin biopsy is negative for residual leukemia cutis. Given she did not receive full intended course of midostaurin during her treatment course, would you consider additional midostaurin as monotherapy maintenance? Or just observe?
Great question! I have a few patients with this exact situation (FLT3 + CBF) and I similarly chose to avoid transplant if MRD negative. It is unlikely that the midostaurin will add actual benefit. While the RATIFY trial did include 1 year of maintenance, there appeared to be no benefit in a post-hoc analysis https://pubmed.ncbi.nlm.nih.gov/33654204/. However, this analysis was unable to detect significant the benefit of mido maintenance because of lack of randomization. If she was able to tolerate, you could consider midostaurin but in my practice, if there are any adverse events then I usually hold and do not think that this significantly impacts relapse or survival rates.
