Promising results for triplet therapy with magrolimab in AML

Triplet therapy of azacitidine, venetoclax, and magrolimab was safe as first-line therapy in patients with acute myeloid leukaemia (AML) and displayed encouraging response rates and overall survival rates even in TP53-mutated AML. The randomised phase 3 ENHANCE-3 trial has been initiated to assess whether this triplet combination can outperform the azacitidine and venetoclax doublet.

The overall survival rate of patients with AML treated with azacitidine and venetoclax in the frontline is 35–40% at 2 years [1]. Furthermore, the complete remission (CR)/complete remission with incomplete count recovery (CRi) rate of patients with relapsed/refractory venetoclax-naïve AML is 30–35% [2]. Thus, there is a clear need to improve health outcomes in patients with AML.

Prof. Naval Daver (Anderson Cancer Center, TX, USA) tested the combination of azacitidine, venetoclax, and magrolimab in a high-risk cohort of patients with newly diagnosed AML (n=43) and in 2 cohorts of patients with relapsed or refractory AML, either venetoclax-naïve (n=18) or venetoclax-experienced (n=18) [3].

In the frontline cohort, the CR/CRi rate was 72% and the CR rate only was 49%. In addition, those with TP53-mutated disease and those with TP53-wildtype disease had comparable outcomes. After a median follow-up time of 14.5 months, the median overall survival (OS) was not reached in de novo participants (n=33) with TP53-wildtype (12-month OS 83%) or TP53-mutated AML (12-month OS 53%). In participants with secondary AML (n=10), the median OS was 7.6 months and 9.6 months in those with TP53-mutated and TP53-wildtype disease, respectively.

Although 90% of the participants had at least 1 grade 3 or higher adverse event (AE), no study treatment discontinuations were reported due to treatment-related AEs. Finally, Prof. Daver noted that anaemia grade ≥3 occurred in 23% of the participants and that this is an issue that should be monitored closely in following studies investigating the triplet combination of azacitidine, venetoclax, and magrolimab.

The phase 3 ENHANCE-3 trial (NCT05079230) will investigate the triplet combination versus azacitidine and venetoclax in newly diagnosed, previously untreated AML patients. In the relapsed/refractory cohorts, the results were not promising (CR/CRi rate venetoclax-naïve [44%]; venetoclax-exposed [11%]) and Prof. Daver mentioned that it is unlikely that the triplet therapy will be further investigated in these patients.

1. Dinardo CD, et al. NEJM. 2020;383:617–629.
2. Dinardo CD, et al. Lancet Haematol. 2020;7(10):e724–e736.
3. Daver N, et al. Phase I/II study of azacitidine, venetoclax and magrolimab for newly diagnosed and relapsed/refractory AML. Abstract 61, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February, 2023