On September 13, 2018, the FDA approved moxetumomab pasudotox-tdfk (Lumoxiti®, AstraZeneca) for adult patients with relapsed or refractory (R/R) hairy cell leukaemia (HCL) who had received at minimum two prior systemic therapies, of which one a purine nucleoside analogue (PNA).

Clinical Data

The Phase 3, pivotal, multicenter, single group CD-ON-CAT-8015-1053 study (NCT01829711) enrolled 80 patients with histologically confirmed HCL (N=77) or an HCL-variant (N=3) requiring treatment based on the presence of cytopenias or splenomegaly. Eligible patients had received prior treatment with at minimum two systemic therapies, including one PNA. All patients were required to have a serum creatinine ≤1.5 mg/dL or creatinine clearance ≥60 mL/min as estimated by the Cockcroft Gault equation at baseline. Upon successful enrollment, participants received intravenous (IV) moxetumomab pasudotox-tdfk 0.04 mg/kg on days 1, 3, and 5 in 28-day cycles for up to 6 cycles or until complete response (CR), progression disease, or unacceptable toxicity.

The primary objective was the blinded independent central review committee (BIRC)-assessed durable CR rate (maintenance of haematologic remission ≥180 days after BIRC-assessed CR) was 30% (24/80 patients; 95% CI, 20-41). The percentage of participants with a CR as assessed by the BIRC was 41% (33/80 patients; 95% CI, 30-53).

Safety

The most common any-grade non-laboratory adverse reactions (ARs) in ≥20% of participants were infusion-related reactions, oedema, nausea, fatigue, headache, pyrexia, constipation, anaemia, and diarrhoea. Common Grade 3/4 ARs reported in ≥ 5% of patients were hypertension, febrile neutropenia, and haemolytic uremic syndrome (HUS).

Permanent discontinuation of moxetumomab pasudotox-tdfk due to ARs occurred in 15% (12/80) of patients. The most common AR resulting in discontinuation was HUS (5%). The most common AR leading to dose delays, omissions, or interruptions was pyrexia (3.8%).

Reference

US FDA website, FDA approves moxetumomab pasudotox-tdfk for hairy cell leukemia [Accessed: 14 September 2018].