COMMODORE trial steers gilteritinib to the fore of AML treatment

Gilteritinib provided significant survival benefit and demonstrated a favourable safety and tolerability profile in Asian patients with relapsed/refractory FLT3-mutated acute myeloid leukaemia (R/R FLT3^mut+ AML) compared with salvage chemotherapy (SC), findings from the phase III COMMODORE trial suggest.

“Gilteritinib significantly prolonged overall survival (OS) and event-free (EFS) compared with SC in patients with R/R FLT3^mut+ AML in Asia,” said Dr Jianxiang Wang from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China, who presented the findings at ASH 2021.

“Due to poor prognosis, treatment options for patients with R/R FLT3^mut+ AML are needed globally,” explained Wang. “Therefore, [we sought] to evaluate the efficacy and safety/tolerability of gilteritinib compared with SC in Asian patients with R/R FLT3^mut+ AML after first-line therapy.”

Wang and colleagues evaluated 234 adult patients (median age 50.5 years, 54 percent male) with R/R FLT3^mut+ AML from China, Russia, Singapore, Thailand, and Malaysia. Participants were randomized 1:1 to receive daily oral gilteritinib 120 mg or SC*. SC was selected by investigators prior to randomization. A majority of the cohort (91 percent) have not received prior FLT3 inhibitors. Baseline FLT3 mutations in the gilteritinib vs SC arms were FLT3-ITD (91 percent vs 83 percent), FLT3-TKD (6 percent vs 12 percent), and both FLT3-ITD and FLT3-TKD (3 percent vs 5 percent). [ASH 2021, abstract 695]

In the intention-to-treat cohort, OS was significantly longer with gilteritinib vs SC, thus meeting the primary study endpoint. The risk of death dropped by ~45 percent with gilteritinib vs SC (median, 9.0 vs 4.7 months; hazard ratio [HR], 0.549; p=0.00126). One-year OS rates were 33 percent with gilteritinib and 23 percent with SC.

Moreover, EFS was significantly longer with gilteritinib vs SC (median, 2.8 vs 0.6 months; HR 0.55; p=0.00004).

Albeit lacking statistical significance, more patients on gilteritinib vs SC achieved complete remission (CR; 16 percent vs 10 percent; treatment difference, 5.9 percent; p=0.1769). In terms of composite** CR, the rate was more than doubled with gilteritinib vs SC (50 percent vs 20 percent; treatment difference, 29.5 percent; p<0.00001).

Compared with the SC arm, the gilteritinib arm had a similar rate of grade ≥3 adverse events (AEs; 97 percent vs 94 percent) but higher rates of serious AEs (74 percent vs 62 percent) and AEs leading to death (20 percent and 14 percent).

However, when adjusted for treatment exposure, safety and tolerability appeared to favour gilteritinib over SC, noted Wang. These were seen in the lower exposure-adjusted rates of serious AEs in the gilteritinib (55.56 events/patient-year [E/PY; grade ≥3] and 6.19 E/PY [serious]) vs the SC arm (164.00 and 12.40 E/PY, respectively), as well as rates of AEs leading to death (0.67 vs 1.5 E/PY).

The most common AEs associated with gilteritinib were anaemia (76 percent), thrombocytopenia (47 percent), pyrexia (42 percent), and increased blood lactate dehydrogenase (42 percent).

Gilteritinib has been approved in several countries and has recently received conditional approval in China for R/R FLT3^mut+ AML treatment. [www.fda.gov/news-events/press-announcements/fda-approves-treatment-adult-patients-who-have-relapsed-or-refractory-acute-myeloid-leukemia-aml; www.astellas.com/us/news/4646; www.astellas.com/us/news/5506, all accessed December 28, 2021]

The superiority of gilteritinib over SC in terms of survival benefit has also been reflected in the phase III ADMIRAL trial. [N Engl J Med 2019;381:1728-1740] “[Our findings] further validate and affirm the clinical efficacy and safety data from the ADMIRAL trial, reinforcing the significant benefit of gilteritinib in R/R FLT3^mut+ AML,” concluded Wang.