Anti-CD70 is safe with hypomethylating agents in AML

Prof. Adrian Ochsenbein (Bern University Hospital, Switzerland) presented the results of the open-label, non-randomised combined phase 1 and 2 study looking at newly diagnosed acute myeloid leukaemia (AML) treatment with hypomethylating agent azacitidine. These results showed that better clinical benefit could be achieved by the addition of the anti-CD70 monoclonal antibody cusatuzumab. Cusatuzumab in combination with azacitidine appeared safe and tolerable [1].

Leukaemia stem cells are known to express the surface markers CD70 and CD27, and there is substantial pre-clinical data to suggest that cusatuzumab blocks CD70–CD27 signalling. The authors hypothesised that combining cusatuzumab with azacitidine would eradicate leukaemia stem cells. This study provided the first-in-human data of this combination.

The study enrolled 12 patients with newly diagnosed AML, who received 1 infusion with cusatuzumab, ranging from 1-20 mg/kg, followed after 14 days with two 28-day cycles of subcutaneous azacitidine (75 mg/m2) from day 1-7 and biweekly cusatuzumab, starting at day 3 of each cycle. The primary endpoint was safety and tolerability. Key secondary endpoints were efficacy, pharmacokinetics, and effect on leukaemia stem cells.

No dose-limiting toxicities were observed in the phase 1 part of the study. One patient receiving a 3 mg/kg dose experienced an adverse event that led to discontinuation. A full list of adverse events per dose is included in the Table.

Table: Most frequent grade 3 or higher treatment-emergent adverse events

The overall response was promising: 100% of patients achieved a response, with 67% (8/12) of patients achieving complete response, 17% (2/12) achieving complete response with incomplete haematological recovery, and 17% (2/12) achieving a partial response. The median time to response was 3.3 months.

The average blast reduction of cusatuzumab monotherapy was 30% and, at the time of best response, the blast reduction was 95% on average. Flow cytometry in 9 patients determined that minimal residual disease could not be detected in 44% of the patient, whereas 56% did have minimal residual disease. A phase 2, dose-expansion study using 10 mg/kg of cusatuzumab is currently ongoing.

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   1. Ochsenbein A, et al. Abstract 234, ASH 2019, 7-10 December, Orlando, USA.

Posted on 5 March 202030 March 2021