DUSP22 AND TP63 REARRANGEMENTS PREDICT OUTCOME OF ALK‐NEGATIVE ANAPLASTIC LARGE CELL LYMPHOMA: A DANISH COHORT STUDY

Abstract

Anaplastic large cell lymphomas (ALCLs) are among the most common systemic peripheral T-cell lymphomas (PTCLs) and are classified into anaplastic lymphoma kinase (ALK) positive and negative subtypes. Overall, patients with ALK-positive ALCLs have outcomes superior to those with ALK-negative ALCLs. However, a single retrospective study identified marked heterogeneity of clinical outcomes among ALK-negative ALCLs based on stratification by rearrangements of DUSP22 or TP63. Here, we sought to validate this observation in an independent, population-based cohort of 138 Danish PTCLs. DUSP22 rearrangements were seen in 5/27 ALK-negative ALCLs (19%) and TP63 rearrangements were seen in 2/27 (7%). Patients with DUSP22-rearranged ALCL had a 5-year overall survival (OS) rate of 80%, similar to that of ALK-positive ALCL (85%). Both patients with TP63-rearranged ALCL died with refractory disease within 2 years of diagnosis. Patients with triple-negative ALCL lacking rearrangements of ALK, DUSP22, and TP63 had an intermediate 5-year OS rate of 33%. Differences in outcomes among genetic subgroups of ALCL were significant (P < 0.02). These findings provide independent evidence that DUSP22 and TP63 rearrangements are strong outcome predictors in ALK-negative ALCL, support routine testing for these alterations in patients with this disease, and open opportunities for risk-adapted therapy based on genetic stratification. Accordingly, the predictive significance of DUSP22 and TP63 rearrangements is currently being evaluated further in the setting of a large Nordic PTCL trial of up-front ASCT (NLG-T-01). Keywords: anaplastic large cell lymphoma (ALCL); gene rearrangement.