The combination of venetoclax and FLAG-IDA salvage therapy as a treatment regimen demonstrated deep remission and a high rate of transition to transplant, particularly in the TP53 wild-type, in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML).

At the 2022 ASH Annual Meeting and Exposition in New Orleans, LA, Sai Prasad Desikan, MD, MD Anderson Cancer Center, Houston, Texas, presented this data from an updated phase 2b study. 

Desikan and coauthors wrote, “Venetoclax with FLAG-IDA demonstrated favorable response rates in the frontline and relapsed or refractory (R/R) setting.” 

A total cohort of 33 patients (>18 years of age) were administered the combination of venetoclax and FLAG-IDA, all of whom had AML and experienced either a lack of response to prior treatment, or relapsed disease, with no prior treatment including the use of venetoclax. All participants had sustained organ functioning to be eligible for this study and treatment combination. 

The median age of this cohort was 47, with a range of 18 to 68 . 70% of patients were administered this regimen as Salvage 1 (for patients who were not responding to other treatments), and 30% of patients were administered this treatment after undergoing stem cell treatment (SCT). 67% of patients had ELN 2017 adverse risk disease. 

Induction consisted of the administration of venetoclax (100mg day 1, 200mg day 2, 400mg day 3, and onwards days 1-14), in combination with FLAG-IDA salvage treatment (30mg/m2 fludarabine days 2 to 6, 1.5g/m2 cytarabine days 2 to 6, 6mg/m2 idarubicin days 4 to 5, and a filgrastim injection days 1 to -7). During consolidation, venetoclax was given at the same administration dosage pattern on days 1 to 7, in combination with 30mg/m2 of fludarabine and 1.5g/m2 of cytarabine, both on days 2 to 4. 

Among the 33 patients in the original cohort, 1 patient was removed due to being too early for accurate response assessment. Results of the 32 remaining patients, who underwent a median of 2 cycles (range: 1 to 4), included an OR of 60% (n=19), a CRc rate of 53%, and 71% of responders (n=12) reaching minimal residual disease (MRD) negativity. In Salvage 1, the ORR was 65% and the CRc was 61%. By ELN risk, ORR was 100% in favorable risk, 50% in intermediate risk, and 48% in adverse risk. CRc was 85% in favorable risk, 50% in intermediate risk, and 43% in adverse risk. A mutation analysis found that ORR and CRc rates for TP53 wild-type vs TP53 mutant was 68% and 14%, versus 64% and 14%. Among the responding patients, 68% (n=13) were given an allogeneic transplant, including 2 patients who transitioned to HMA + VEN and sorafenib maintenance before transplant. 

Researchers followed up with patients at a median of 15.8 months to find that the OS and DOR were 27 months and NR. OS in TP53 wild-type vs TP53 mutant was NR and 5.4 months with a 12-month OS of 68% and 17%. A total of 2 deaths occurred within 60 days in patients with persistent leukemia. 

Dr. Desikan and co-authors concluded, “this regimen is associated with deep remissions and a high rate of transition to transplant inpatients with R/R AML, particularly in TP53 wild-type.”

Source: 

Desikan SP, Konopleva M, Takahashi K, et al. Updated Phase IIb Results of Venetoclax with FLAG-IDA in Relapsed or Refractory Acute Myeloid Leukemia. Presented at ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 221