The primary results of the phase II RADIUS study (NCT01883362) were reported at the 60th American Society of Hematology Annual Meeting & Exposition by Richard Thomas T. Maziarz from OR Health Sciences University, Portland, US. The phase II, randomized, exploratory RADIUS study is assessing whether the addition of midostaurin, a multi-targeted tyrosine kinase inhibitor, to standard of care (SOC) after allogeneic stem cell transplantation (alloSCT) can reduce the risk of relapse in patients with fms-like tyrosine kinase 3-internal tandem duplication positive (FLT3-ITD+) acute myeloid leukemia (AML).
In this study, 60 patients with FLT3-ITD+ AML who underwent myeloablative alloSCT in first complete remission (CR1) were randomized to receive SOC with (n = 30; median age = 48 years) or without (n = 30; median age = 56 years) midostaurin (50 mg twice daily, continuous 28 day cycles). Treatment began 28–60 days after alloSCT. The median duration of exposure in the midostaurin arm was 10.5 months (range: 1.2–11.5 months) and the median dose intensity was 93 mg/day (range, 25–100 mg/day).
The primary objective of the study was relapse-free survival (RFS) at 18 months post-alloSCT. Key secondary objectives include safety and RFS at 24 months post-alloSCT.
- RFS at 18 months post-alloSCT in the midostaurin plus SOC and SOC alone arm, respectively: 89% (95% CI, 69–96) vs 76% (95% CI, 54–88), HR = 0.46 (95% CI, 0.12–1.86), P = 0.2655
- RFS at 24 months post-alloSCT in the midostaurin plus SOC and SOC alone arm, respectively: 85% (95% CI, 64–94) vs 76% (95% CI, 54–88), HR = 0.60 (95% CI, 0.17–2.14), P = 0.4297
- The most common any-grade adverse event (AE) in the SOC and midostaurin plus SOC arm was vomiting: 23% vs 73%, respectively
- The most common any-grade AEs with midostaurin were low-grade gastrointestinal events
- Rates of graft-versus-host disease (GvHD) were similar between SOC and midostaurin plus SOC arms
- Acute GvHD: 70% vs 73%
- Chronic GvHD: 47% vs 37%
The speaker stated that maintenance therapy with midostaurin may contribute to a 54% relative reduction in the risk of relapse versus SOC alone. In addition, midostaurin was well tolerated and did not increase the rates or severity of GvHD.
In an interview with the AGP, Richard Maziarz concluded that the midostaurin monotherapy can be safely administered in the post-transplant setting and may improve outcomes in patients who undergo alloSCT in CR1.