Mark J. Levis, MD, PhD, the program leader of the Hematologic Malignancies and Bone Marrow Transplant Program at Sidney Kimmel Comprehensive Cancer Center, and a professor of Oncology at Johns Hopkins Medicine, discusses data from the phase 3 BMT CTN 1506/MORPHO trial (NCT02997202) of gilteritinib (Xospata) as maintenance therapy following allogeneic stem cell transplant (ASCT) in patients With 

-ITD–positive acute myeloid leukemia (AML).

Patients who achieved a morphologic remission following 1 or 2 induction therapies and underwent ASCT were randomly assigned to receive gilteritinib at 120 mg or placebo once per day for 2 years as maintenance therapy. Data presented at the 2023 EHA Congress showed that the study failed to reach its primary end point for relapse-free survival (RFS). Levis says patients in the gilteritinib arms achieved a numerical but not statistically significant improvement in RFS (HR, 0.679; 95% CI, 0.459-1.005; 2-sided 

Although a statistically significant improvement in RFS was not observed in the overall population, Levis notes that looking at the RFS effect of gilteritinib vs placebo based on minimal residual disease (MRD) status provides important context. In patients who were MRD positive, gilteritinib (n = 89) led to an improvement in RFS over placebo (n = 91; HR, 0.515; 95% CI, 0.316-0.838; 

 = .0065). In those who were MRD negative, the RFS curves were similar for gilteritinib (n = 89) and placebo (n = 87; 

The MRD data helped identify those patients who could potentially benefit from gilteritinib following ASCT, Levis explains. He explains that there could also be patients classified as MRD negative who could benefit from the use of maintenance gilteritinib.

Since gilteritinib is associated with myelosuppression, monitoring blood counts is important during its administration, Levis says, adding that dose reductions for the agent and adjustments of concomitant medications are necessary to keep patients on treatment.

Data from MORPHO could ultimately help guide the management of patients with 

-ITD–positive AML by showing which factors could determine whether those in this patient population could benefit from FLT3 inhibition, Levis concludes.

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Mark J. Levis, MD, PhD, discusses data from the phase 3 BMT CTN 1506/MORPHO trial of gilteritinib as maintenance therapy following allogeneic stem cell transplant in patients With FLT3-ITD–positive acute myeloid leukemia.

Dr Levis on Maintenance Gilteritinib After ASCT in FLT3-ITD+ AML

Mark James Levis, MD, PhD, program leader of Hematologic Malignancies and Bone Marrow Transplant Program at Sidney Kimmel Comprehensive Cancer Center, and professor of oncology, Johns Hopkins Medicine, discusses an analysis of gilteritinib (Xospata) in patients with relapsed/refractory 

-mutated acute myeloid leukemia (AML) harboring other common co-mutations or a high 

-internal tandem duplication (ITD) allelic ratio.

Following data from the phase III ADMIRAL study, which led to the FDA’s decision to approve gilteritinib in patients with relapsed/refractory 

-mutated AML, Levis and colleagues performed next-generation sequencing on 37 different mutated genes in AML to compare the effectiveness of gilteritinib with salvage chemotherapy.

From the data, four major cohorts emerged: 

 mutations. Overall, gilteritinib had a clearly greater response rate than chemotherapy across all cohorts, says Levis.

The results pertaining to allelic ratio were as expected, he adds. Those with a higher allelic ratio (≥ 0.77), and thus more tumor present, performed worse than those with a lower ratio. However, gilteritinib was found to confer longer OS compared with chemotherapy in patients with a high (7.1 months versus 4.3 months, respectively) or low 

-ITD allelic ratio (10.6 months versus 6.9 months, respectively).

The most intriguing piece of data, according to Levis, was a remarkably impressive OS of 10.8 months in gilteritinib-treated patients with both 

 mutations compared with just 5 months in those who received chemotherapy. Levis says these data raise the question of whether gilteritinib should be moved into the upfront setting for these patients in the future.

Mark James Levis, MD, PhD, program leader of Hematologic Malignancies and Bone Marrow Transplant Program at Sidney Kimmel Comprehensive Cancer Center, and professor of oncology, Johns Hopkins Medicine, discusses an analysis of gilteritinib in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia harboring other common co-mutations or a high FLT3-internal tandem duplication allelic ratio.

Mark James Levis, MD, PhD

Articles

Dr Levis on Maintenance Gilteritinib After ASCT in FLT3-ITD+ AML

Dr. Levis on Gilteritinib in Relapsed/Refractory FLT3-Mutated AML