Treatment with midostaurin plus intensive chemotherapy appeared safe among older adults with acute myeloid leukemia and a FLT3 internal tandem duplication mutation, according to results of a prospective, phase 2 trial published in Blood.
Midostaurin (Rydapt, Novartis), a multitargeted kinase inhibitor, also significantly improved EFS among older as well as younger patients with FLT3-IDT AML compared with historical controls.
“After the approval by FDA and [European Medicines Agency] of midostaurin for patients with FLT3-mutated AML, our hypothesis-generating trial is the first to show efficacy and safety data of midostaurin in older patients with FLT3-[internal tandem duplication (ITD)] given in combination with intensive chemotherapy, and as single-agent maintenance after [allogeneic hematopoietic stem cell transplantation],” Richard F. Schlenk, MD, professor of internal medicine at the University Hospital of Ulm, Germany, and colleagues wrote.
In the prospective, multi-institutional study, Schlenk and colleagues evaluated 284 patients (aged 18-60 years, n = 198; aged 61-70 years, n = 86) with AML and centrally verified FLT3-ITD. All patients received induction therapy with idarubicin, cytarabine and etoposide and midostaurin. Patients who achieved complete remission or complete remission with incomplete hematological recovery underwent consolidation therapy, with allogeneic HSCT performed during first complete remission at the researchers’ discretion. Patients who could not undergo transplantation received up to four cycles of high-dose cytarabine.
Results showed that by the end of induction therapy, 217 patients (74.6%) attained complete remission or complete remission with incomplete hematological recovery, 51 patients (18%) had refractory disease and 16 patients (5.6%) had died.
Most patients (72.4%) in complete remission or complete remission with incomplete hematological recovery subsequently received allogeneic HSCT. Ninety-seven patients (34%) underwent maintenance therapy, including 75 after allogeneic HSCT (median time on maintenance, 9 months) and 22 after consolidation with cytarabine (median maintenance, 10.5 months).
Researchers observed 2-year EFS rates of 34% (95% CI, 24-47) among older patients vs. 39% (95% CI, 33-47) for younger patients, and 2-year OS rates of 46% (95% CI, 35-59) vs. 53% (95% CI, 46-61).
Researchers also conducted a propensity score-weighted analysis comparing EFS rates with those of 415 historical controls from five prospective trials. Results showed significant risk reduction for an event with midostaurin (HR = 0.58; 95% CI, 0.48-0.7). Subgroup analysis based on age group revealed significant differences in both younger (HR = 0.61; 95% CI, 0.49-0.76) and older patients (HR = 0.42; 95% CI, 0.29-0.61).
“In summary, we show that midostaurin plus intensive chemotherapy can be safely administered also in older patients,” the researchers wrote. “Compared to historical controls, midostaurin significantly improved EFS. Allogeneic [HSCT] in first remission after midostaurin and chemotherapy is feasible and highly effective irrespective of age.” – Jennifer Byrne
Disclosures: Schlenk reports advisory board roles, honoraria and research funding from Novartis. Please see the full study for all other authors’ relevant financial disclosures.