The following article features coverage from the 2021 Annual Meeting of the Society of Hematologic Oncology (SOHO). Click here to read more of Hematology Advisor‘s conference coverage.

According to the results of a study presented at the virtual program of the Annual Meeting of the Society of Hematologic Oncology (SOHO), FLAG-IDA (Fludarabine, Cytarabine, Idarubicin, and G-CSF) plus venetoclax (VEN) induction and consolidation yields high measurable residual disease (MRD)-negative composite complete remission (CRc) rates in patients with newly diagnosed acute myeloid leukemia (ND-AML).

The ongoing phase 1b/2 study (ClinicalTrials.gov Identifier: NCT03214562) is evaluating FLAG-IDA with VEN in adult patients with ND-AML and relapsed/refractory (R/R) AML. At the meeting, Curtis Lachowiez, MD, of The University of Texas MD Anderson Cancer Center, Houston, TX, presented outcomes from patients with ND-AML (n=41) enrolled in the phase 2 portion of the study.

The primary objective is to determine the overall activity of FLAG-IDA+VEN, and key secondary objectives include overall response rate (ORR), CRc, overall survival (OS), event-free survival (EFS), and duration of response (DOR).


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Among the 41 patients with ND-AML, 54% were female, and the median age was 44 years (range, 20-65 years). European LeukemiaNet (ELN) was favorable in 20%, intermediate in 37%, and adverse in 44% of patients.

The ORR was 98%, comprising a CR of 73% (n=30), a CR with partial hematologic recovery of 12% (n=5), a CR with incomplete hematologic recovery of 2% (n=1), and a morphologic leukemia-free state rate of 10% (n=4), and the corresponding CRc rate was 88% (n=36). MRD-negative status was achieved in 92% of CRc patients (n=33). Only 1 patient had no response/progressive disease.

Patients received a median of 2 treatment cycles (range, 1-6), and the median cycle length was 31 days for cycle 1 and 41 days for each cycle 2 and 3. Overall, 66%  (n=27) of patients transitioned to allogeneic hematopoietic stem cell transplant (HSCT). The median DOR was not reached (95% confidence interval, 17-NR months). No 30- or 60-day mortality occurred.

The combination of FLAG-IDA with Venetoclax demonstrated an expected safety profile. Common adverse events included febrile neutropenia (39%), pneumonia (24%), bacteremia (19%), and cellulitis, pyrexia and sepsis (each 7%).

Relapse occurred in 8 patients (ELN intermediate: n=3; ELN adverse: n=5), including all patients with baseline TP53 mutations (n=4), and 4 of these patients died. Most relapses (5 of 8) and deaths (3 of 4) occurred after HSCT.

After a median follow up of 15 months, the 1-year EFS and OS rates of 76% and 96%, respectively; the median EFS and OS had not been reached.

“In conclusion, we see that FLAG-IDA with venetoclax in newly diagnosed AML is associated with a high composite CR rate in de novo and secondary in therapy related AML, and MRD negativity was attained in over 90% of patients who achieve a composite CR,” said Dr Lachowiez. “FLAG-IDA+VEN is associated with an acceptable safety profile, with infectious complications being most common, and resulted in a high rate of transition to allogeneic transplantation to date.”

Long-term follow up to confirm the results is ongoing.

Read more of Hematology Advisor’s coverage of SOHO 2021 by visiting the conference page.

Reference

Lachowiez C, Takahashi K, Loghavi S, et al. Venetoclax combined with FLAG-IDA induction and consolidation in newly diagnosed acute myeloid leukemia. Paper presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 8-11, 2021. Abstract AML-204.