ALK-negative anaplastic large cell lymphoma with <i>DUSP22</i> rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study

Abstract

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

<i>DUSP22</i>-rearranged ALK-negative anaplastic large cell lymphoma is a pathogenetically distinct disease but can have variable clinical outcome

“…The study by Sibon and colleagues represents the largest series to date of 47 cases of DUSP22R ALK-negative ALCL derived from the TENOMIC database, a translational lymphoma research consortium of the LYSA group. In total, 47/104 (45%) cases harboured a DUSP22R which is significantly higher than other reports, and the authors acknowledge a selection bias as cases are submitted to the LYSA TENOMIC database with an aim of compiling those of clinical interest (13). In the subset enrolled on clinical trials, estimates are more in keeping with other studies (23-35%).…”

“…The treatment landscape of ALCL has changed over the last decade with the approval of brentuximab vedotin (BV) in relapsed/refractory ALCL(15) and more recently, approval of CHP (cyclophosphamide, doxorubicin, prednisone)-BV in newly diagnosed systemic ALCL based on superior PFS and OS over CHOP, as shown in the ECHELON-2 study in CD30+ PTCLs (16). In the LYSA study, survival was notably poor from first relapse/progression, regardless of DUSP22R status suggesting that any prognostic relevance may diminish in this high risk setting (4 year OS 21%(DUSP22R) vs 34% (triple negative) P=0.62)(Figure 5A accompanying article) (13). The use of BV in relapsed/refractory ALCL improved outcome across genetic subgroups but similarly, there was no outcome difference noted.…”

“…The use of BV in relapsed/refractory ALCL improved outcome across genetic subgroups but similarly, there was no outcome difference noted. (Figure 5E/F accompanying article) (13). Of note, the prognostic impact of DUSP22R in treatment naïve ALK-negative ALCL patients treated with CHP-BV remains unknown.…”

“…In this issue of Haematologica, two studies have further evaluated the pathologic characteristics and prognostic significance of DUSP22R ALK-negative ALCL (13,14). The study by Sibon and colleagues represents the largest series to date of 47 cases of DUSP22R ALK-negative ALCL derived from the TENOMIC database, a translational lymphoma research consortium of the LYSA group.…”

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“…DUSP‐22 rearranged ALK‐ ALCL have a characteristic GEP signature characterized by downregulation of JAK/STAT pathway genes, global DNA hypomethylation, and an immunogenic phenotype 30,31 . In earlier reports, DUSP22 rearrangement was associated with a favorable prognosis with 5‐year OS rates of 40–90% equivalent to ALK+ ALCL, but recent studies including a large series from the LYSA group showed that higher risk groups with poor performance status had a 4‐year PFS and OS of only 17% and 21%, respectively 32,33 . The outcomes of DUSP‐22 rearranged ALCL are still improved compared with ALK‐ ALCL with TP63 rearrangements or triple‐negative ALCL lacking all 3 rearrangements.…”