Background
Phase 3 pivotal, open-label, single-arm trial (study 1053). N=80 patients with R/R classic HCL who had received ≥2 prior therapies including a purine analog. Moxetumomab pasudotox-tdfk (Lumoxiti) is a recombinant anti-CD22 immunotoxin (CD22-targeted, Pseudomonas exotoxin PE38 payload) with potent cytotoxicity in CD22-expressing B-cell malignancies. Pivotal trial supporting FDA approval. Published JCO 2018.
Interventions and follow up
Regimen: Moxetumomab pasudotox 40 µg/kg IV days 1, 3, 5 of every 28-day cycle for up to 6 cycles — relapsed/refractory hairy-cell leukemia
Primary endpoint: Durable CR rate (CR with hematologic remission >180 days)
mFollow up: 24.6 months
Primary endpoint: Durable CR rate (CR with hematologic remission >180 days)
mFollow up: 24.6 months
Results
CR rate: 41%
ORR: 75%
uMRD (in CR patients): 85%
mDOR (CR patients): Not reached at 24 months
mDOR (PR patients): 5.1 months
2-yr DFS (uMRD-negative CRs): 97%
ORR: 75%
uMRD (in CR patients): 85%
mDOR (CR patients): Not reached at 24 months
mDOR (PR patients): 5.1 months
2-yr DFS (uMRD-negative CRs): 97%
Adverse events
Class-specific: Hemolytic uremic syndrome any grade 7.5%, grade ≥3 5%; capillary leak syndrome any grade 7.5%, grade ≥3 1.3% — key safety signals requiring monitoring
Constitutional/Metabolic: Edema 39%; hypoalbuminemia 39%; fatigue 31%; nausea 35%
Infusion/Other: Infusion-related reactions 8.8%; grade ≥3 AEs 63%; discontinuation due to AEs 10%; no treatment-related deaths
Constitutional/Metabolic: Edema 39%; hypoalbuminemia 39%; fatigue 31%; nausea 35%
Infusion/Other: Infusion-related reactions 8.8%; grade ≥3 AEs 63%; discontinuation due to AEs 10%; no treatment-related deaths
Conclusions
Moxetumomab pasudotox achieved a 41% CR rate and 75% ORR in heavily pretreated R/R HCL with durable remissions (97% 2-yr DFS in uMRD-negative CRs), supporting FDA approval. HUS and capillary leak syndrome are key signals requiring patient education and monitoring but are manageable with hydration and early recognition.
Key Limitations
Single-arm trial: No comparator
Cumbersome schedule: Multi-day IV dosing per cycle with HUS/CLS monitoring requirements
Commercial withdrawal: Manufacturer voluntarily withdrew Lumoxiti from the US market in 2023 for business reasons, limiting current availability
Cumbersome schedule: Multi-day IV dosing per cycle with HUS/CLS monitoring requirements
Commercial withdrawal: Manufacturer voluntarily withdrew Lumoxiti from the US market in 2023 for business reasons, limiting current availability
Clinical Context
Moxetumomab pasudotox was FDA-approved in September 2018 for R/R HCL after ≥2 prior therapies including a purine analog. It targets CD22 rather than BRAF, retaining activity regardless of BRAF status. However, the manufacturer withdrew the drug from the US market in 2023, so BRAF-targeted therapy (vemurafenib±rituximab, dabrafenib+trametinib) and venetoclax-based regimens are now the principal R/R options.