Researchers observed encouraging response rates in older or high-risk patients with newly diagnosed acute myeloid leukaemia (AML) who were treated with the triplet combination therapy of azacitidine, venetoclax and magrolimab on a Phase Ib/II trial.

The newly diagnosed cohort had an 80% overall response rate (ORR), and the median overall survival (OS) was not yet reached at a median follow-up of 9.2 months. 

Naval Daver, M.D., associate professor of Leukemia, presented study results at ASH 2022.

“We are encouraged by the promising evidence of this triplet therapy as a treatment option for older or unfit patients with AML,” Daver said. “We will continue to expand the trial to include more patients, and we have initiated an international Phase III randomised study evaluating the triplet therapy versus the doublet azacitidine-venetoclax. If the study is positive, it could establish a new frontline standard of care for these patients.”

About 50-55% of patients with AML are considered older or unfit for intensive chemotherapy.

Frontline treatment with azacitidine and venetoclax achieves response rates of 65-70% in newly diagnosed patients, but most patients will relapse and those with TP53 mutations continue to have poor outcomes, with median OS of less than six months.

Magrolimab is an anti-CD47 antibody that works to block the “don’t eat me signal” on leukaemia cells. In a previous trial, it demonstrated efficacy with azacitidine in newly diagnosed AML, with an especially encouraging signal of response and survival in frontline TP53-mutated AML.

The current trial enroled 74 patients across two cohorts.

The first cohort enroled 45 frontline patients aged 75 or older with documented comorbidities that made them ineligible for intensive therapy or with adverse risk factors and/or a TP53 mutation, regardless of age.

This cohort included 27 patients with a TP53 mutation and 14 without.

The second cohort enroled 29 patients with relapsed/refractory (R/R) disease.

All patients who received at least one dose of any of the three study drugs were included for response and adverse events.

Eighteen patients experienced greater than grade 3 anaemia, and the most common non-haematologic side effects were febrile neutropenia, pneumonia, hyperbilirubinemia, transaminitis, creatine elevation and hypokalemia. 

In the newly diagnosed cohort, the ORR in patients with and without TP53 mutations was 74% and 93%, respectively.

Median OS was not yet reached for either group of patients.

Responses in patients with R/R disease with prior venetoclax treatment were modest, and the cohort was closed for futility.

Patients with R/R disease without venetoclax exposure still are being enroled.

Source: The University of Texas MD Anderson Cancer Center