ALK-negative anaplastic large cell lymphoma (ALCL) comprises subgroups harboring rearrangements of DUSP22 (DUSP22-R) or TP63 (TP63-R). Two studies respectively reported 90% and 40% 5-year overall survival (OS) in 21 and 12 DUSP22-R/TP63-not rearranged (NR) patients, making the prognostic impact of DUSP22-R unclear. Here, 104 newly diagnosed ALK-negative ALCL patients (including 37 from first-line clinical trials) from the LYSA TENOMIC database were analyzed by break-apart FISH assays for DUSP22-R and TP63-R. There were 47/104 (45%) DUSP22-R and 2/93 (2%) TP63-R cases, including one DUSP22-R/TP63-R. DUSP22-R tumors showed more frequent CD3 expression (62% versus 35%, P=0.01), and less commonly a cytotoxic phenotype (27% versus 82%; P<0.001). At diagnosis, DUSP22-R ALCL patients had more frequent bone involvement (32% versus 13%, P=0.03). The patient with DUSP22-R/TP63-R ALCL had a rapidly fatal outcome. After a median followup of 4.9 years, 5-year progression-free survival (PFS) and OS of 84 patients without TP63-R treated with curative intent anthracycline-based chemotherapy were 41% and 53%, respectively. According to DUSP22 status, 5-year PFS was 57% for 39 DUSP22-R versus 26% for 45 triple-negative (DUSP22-NR/TP63-NR/ALK-negative) patients (P=0.001). The corresponding 5-year OS rates were 65% and 41%, respectively (P=0.07). In multivariate analysis, performance status and DUSP22 status significantly affected PFS, and distinguished four risk groups, with 4-year PFS and OS ranging from 17% to 73% and 21% to 77%, respectively. Performance status but not DUSP22 status impacted OS. The use of Brentuximab vedotin (BV) in relapsed/refractory patients improved OS2 independently of DUSP22 status. Our findings support the biological and clinical distinctiveness of DUSP22-R ALK-negative ALCL. Its relevance to outcome in patients receiving frontline BV remains to be determined.
Figures & Tables
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.