ALK-negative anaplastic large cell lymphoma with <i>DUSP22</i> rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study
David Sibon,
Bettina Bisig,
Christophe Bonnet,
Elsa Poullot,
Emmanuel Bachy,
Doriane Cavalieri,
Virginie Fataccioli,
Cloe Bregnard,
Fanny Drieux,
Julie Bruneau,
Francois Lemonnier,
Aurelie Dupuy,
Celine Bossard,
Marie Parrens,
Krimo Bouabdallah,
Nicolas Ketterer,
Gregoire Berthod,
Anne Cairoli,
Gandhi Damaj,
Olivier Tournilhac,
Jean-Philippe Jais,
Philippe Gaulard,
Laurence de Leval
Affiliations
David Sibon
Lymphoid Malignancies Department, Henri-Mondor University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 94000 Créteil, France; Faculty of Medicine and Health, Campus Henri Mondor, Paris-Est Créteil University, 94000 Créteil
Bettina Bisig
Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University
Christophe Bonnet
Hematology Department, Liège University Hospital
Elsa Poullot
Faculty of Medicine and Health, Campus Henri Mondor, Paris-Est Créteil University, 94000 Créteil, France; Department of Pathology, Henri Mondor University Hospital, Créteil
Emmanuel Bachy
Hematology Department, Lyon-Sud University Hospital
Doriane Cavalieri
Hematology Department, Clermont-Ferrand University Hospital
Virginie Fataccioli
Faculty of Medicine and Health, Campus Henri Mondor, Paris-Est Créteil University, 94000 Créteil, France; Department of Pathology, Henri Mondor University Hospital, Créteil
Cloe Bregnard
Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University
Fanny Drieux
Pathology Department, Henri Becquerel Cancer Center
Julie Bruneau
Pathology Department, Necker University Hospital
Francois Lemonnier
Lymphoid Malignancies Department, Henri-Mondor University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 94000 Créteil, France; Faculty of Medicine and Health, Campus Henri Mondor, Paris-Est Créteil University, 94000 Créteil
Aurelie Dupuy
Faculty of Medicine and Health, Campus Henri Mondor, Paris-Est Créteil University, 94000 Créteil
Celine Bossard
Pathology Department, Nantes University Hospital
Marie Parrens
Pathology Department, Bordeaux University Hospital
Krimo Bouabdallah
Hematology Department, Bordeaux University Hospital
Nicolas Ketterer
Clinique Bois-Cerf, Lausanne
Gregoire Berthod
Hospital Center for Valais Romand (CHVR), Martigny Hospital, CH-1920, Martigny
Anne Cairoli
Service of Hematology, Department of Oncology, Lausanne University Hospital and Lausanne University, Lausanne
Gandhi Damaj
Institut d'Hématologie de Basse-Normandie, Caen University Hospital
Olivier Tournilhac
Hematology Department, Clermont-Ferrand University Hospital
Jean-Philippe Jais
Department of Biostatistics, Necker University Hospital
Philippe Gaulard
Faculty of Medicine and Health, Campus Henri Mondor, Paris-Est Créteil University, 94000 Créteil, France; Department of Pathology, Henri Mondor University Hospital, Créteil
Laurence de Leval
Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University
ALK-negative anaplastic large cell lymphoma (ALCL) comprises subgroups harboring rearrangements of DUSP22 (DUSP22- R) or TP63 (TP63-R). Two studies reported 90% and 40% 5-year overall survival (OS) rates in 21 and 12 DUSP22-R/TP63- not rearranged (NR) patients, respectively, 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 fluorescence in situ hybridization 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 case. DUSP22-R tumors more frequently showed CD3 expression (62% vs. 35%, P=0.01), and less commonly a cytotoxic phenotype (27% vs. 82%; P<0.001). At diagnosis, DUSP22- R ALCL patients more frequently had bone involvement (32% vs. 13%, P=0.03). The patient with DUSP22-R/TP63-R ALCL had a rapidly fatal outcome. After a median follow-up of 4.9 years, 5-year progression-free survival (PFS) and OS rates 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 influenced OS. The use of brentuximab vedotin in relapsed/refractory patients improved OS 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 brentuximab vedotin remains to be determined.
