AcSé-Crizotinib (ALK+ ALCL)

Background

Prospective, single-arm cohort within the French AcSé-crizotinib basket trial. 24 evaluable patients with relapsed/refractory ALK-positive systemic ALCL (median 2 prior lines, including brentuximab vedotin in most). ALK+ sALCL universally harbors NPM1-ALK or variant ALK fusions. Crizotinib, the first ALK inhibitor (approved for ALK+ NSCLC), was tested as a rational targeted approach in ALK-rearranged lymphoma.

Interventions and follow up

Regimen: Crizotinib 250 mg PO twice daily continuously in ALK+ R/R anaplastic large cell lymphoma (pediatric and adult cohorts)
Primary endpoint: Objective response rate
Median follow-up: ~60 months

Results

ORR (primary): 67% (95% CI 47–82%)
CR rate: 50%
Median DoR: 43.3 months
Median PFS: not reached in responders
3-year OS: 63%

Adverse events

Hematologic: Grade ≥3 neutropenia 17%
Ophthalmologic/cardiac: Visual disturbances any grade 38% (ALK inhibitor class effect); bradycardia any grade 13%
Gastrointestinal/overall: Nausea any grade 50%; grade ≥3 AEs 29%; no treatment-related deaths

Conclusions

Crizotinib achieved a 67% ORR (50% CR) with durable responses (median DoR 43.3 months, 3-year OS 63%) in R/R ALK+ sALCL, establishing ALK inhibition as a highly effective strategy in this molecularly defined PTCL subtype, with activity even in a post-BV population.

Key Limitations

Very small single-arm cohort (n=24) mixing pediatric and adult patients without a comparator. Acquired ALK resistance mutations can emerge on continuous therapy. The optimal duration and role versus next-generation ALK inhibitors (e.g., alectinib, lorlatinib) remain undefined.

Clinical Context

Crizotinib is not specifically FDA or EMA approved for ALCL (its lymphoma data derive from basket and pediatric programs), though it is approved for ALK+ NSCLC. ESMO recognizes ALK inhibition as an active option for R/R ALK+ sALCL, particularly after BV failure; trial enrollment is encouraged given limited prospective data.

References