Studies are increasingly suggesting that posttransplant maintenance therapy may improve this outcome. For example, the small, randomized, phase 2 SORMAIN study presented at the 2018 annual meeting of the American Society of Hematology showed a signal for benefit with posttransplant maintenance with the TKI sorafenib. Data regarding midostaurin in this setting are limited, Dr. Maziarz noted.
The RADIUS trial was a small study designed to look for a similar signal with midostaurin and thus was not adequately powered to detect a statistical difference between the arms, he explained.
RADIUS included 60 AML patients aged 18-70 years who underwent myeloablative alloSCT and were in their first complete remission. The primary endpoint was relapse-free survival (RFS) at 18 months after transplant. Results were presented at ASH 2018.
RFS was 89% in 16 of 30 patients who were randomized to receive 50 mg of midostaurin twice daily along with standard-of-care (SOC) treatment and completed 12 4-week cycles. This compared with an RFS rate of 76% in 14 of 30 patients who received SOC only and completed 12 cycles (hazard ratio, 0.46).
The predicted relative reduction in the risk of relapse with the addition of midostaurin was 54%, and at 24 months, both RFS and overall survival were 85% in the midostaurin group and 76% in the SOC-only group, Dr. Maziarz reported.
The median duration of exposure to midostaurin was 10.5 months and the median dose intensity was 93 mg/day, indicating that full-dose therapy was achievable in most patients who stayed on the study.
Treatment was generally well tolerated; there was a comparable number of early discontinuations in the midostaurin and SOC-only arms. The discontinuations were caused mainly by adverse events (typically gastrointestinal toxicities) in the midostaurin arm and by consent withdrawal in the SOC-only arm, he said, adding that there were no significant differences between the groups with respect to serious adverse events or acute or chronic graft-versus-host disease.
Following the presentation of the primary RADIUS results at ASH 2018, an exploratory analysis was conducted to assess midostaurin’s inhibitory effects on FLT3 in plasma.
FLT3 plasma inhibitor activity, assessed by coculturing plasma samples taken on the first day of the treatment cycles with the FLT3-positive AML to look for a reduction in pFLT3, was evaluable in 28 patients in each arm.
“What we see is when you start there are high levels of FLT3, but the pFLT3 drops significantly with exposure to the plasma,” he said, noting that the effect was most prominent during the first two cycles of therapy.