Credit: Rhoda Baer
Adding the Plk1 inhibitor volasertib to chemotherapy can prolong survival in older patients with previously untreated acute myeloid leukemia (AML), researchers have reported in Blood.
In a phase 2 study, AML patients aged 65 or older who were ineligible for intensive induction therapy had higher response and survival rates when they received volasertib plus low-dose cytarabine (LDAC), compared to LDAC alone.
However, adverse events, such as febrile neutropenia and infections, were more common with volasertib.
“These clinical trial results . . . are important and have informed future research for this rare disease, where new treatment options are greatly needed,” said study author Hartmut Döhner, MD, of the University Hospital Ulm in Germany.
“The established approach to treat younger AML patients is an intensive chemotherapy regimen, [but] older patients often cannot tolerate these chemotherapy doses and have very limited treatment options.”
To test volasertib as a potential option, the researchers enrolled and treated 87 patients with previously untreated AML who were ineligible for intensive induction therapy. Their median age was 75 years.
Patients received LDAC at 20 mg BID subcutaneously on days 1 through 10 (n=45) or LDAC plus volasertib at 350 mg intravenously on days 1 and 15, every 4 weeks (n=42). Overall, patient demographics and baseline disease characteristics were balanced between the treatment arms.
The response rate (complete response or complete response with incomplete blood count recovery) was more than doubled for patients receiving volasertib and LDAC compared to LDAC alone. The rates were 31% (13/42) and 13.3% (6/45), respectively (odds ratio, 2.91; P=0.052).
Responses in patients receiving volasertib and LDAC were observed across all genetic groups, including 5 of 14 patients with adverse genetics.
Remissions with the combination treatment appeared to be more durable than those observed with LDAC alone. The median relapse-free survival was 18.5 months and 10.0 months, respectively.
The median event-free survival was prolonged in patients receiving volasertib as well. Their event-free survival was 5.6 months, compared to 2.3 months for patients who received LDAC alone (hazard ratio 0.57,
P=0.021).
Patients who received volasertib also experienced improvements in overall survival. The median overall survival was 8.0 months for the volasertib arm and 5.2 months for the LDAC-alone arm (hazard ratio 0.63; P=0.047).
Patients receiving volasertib and LDAC had higher rates of adverse events than patients in the LDAC-alone arm. Events of note included grade 3 febrile neutropenia (38% vs 7%), grade 3 infections (38% vs 7%) and grade 3 gastrointestinal events (21% vs 7%).
Based on these results, researchers are now investigating volasertib in combination with LDAC in a randomized, double-blind, phase 3 trial for AML called POLO-AML-2.
