Gray zone lymphoma with features intermediate between classicalHodgkin lymphoma and diffuse largeB‐cell lymphoma:Characteristics, outcomes, and prognostication among a large multicenter cohort

Abstract

Gray zone lymphoma (GZL) with features between classical Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) is a recently recognized entity reported to present primarily with mediastinal disease (MGZL). We examined detailed clinical features, outcomes, and prognostic factors among 112 GZL patients recently treated across 19 North American centers. Forty-three percent of patients presented with MGZL, whereas 57% had non-MGZL (NMGZL). NMGZL patients were older (50 versus 37 years, P 5 0.0001); more often had bone marrow involvement (19% versus 0%, P 5 0.001); >1 extranodal site (27% versus 8%, P 5 0.014); and advanced stage disease (81% versus 13%, P 5 0.0001); but they had less bulk (8% versus 44%, P 5 0.0001), compared with MGZL patients. Common frontline treatments were cyclophosphamide-doxorubicin-vincristine-prednisone 1/2 rituximab (CHOP1/2R) 46%, doxorubicin-bleomycin-vinblastine-dacarbazine 1/2 rituximab (ABVD1/2R) 30%, and doseadjusted etoposide-doxorubicin-cyclophosphamide-vincristine-prednisone-rituximab (DA-EPOCH-R) 10%. Overall and complete response rates for all patients were 71% and 59%, respectively; 33% had primary refractory disease. At 31-month median follow-up, 2-year progression-free survival (PFS) and overall survival rates were 40% and 88%, respectively. Interestingly, outcomes in MGZL patients seemed similar compared with that of NMGZL patients. On multivariable analyses, performance status and stage were highly prognostic for survival for all patients. Additionally, patients treated with ABVD1/2R had markedly inferior 2-year PFS (22% versus 52%, P 5 0.03) compared with DLBCL-directed therapy (CHOP1/2R and DA-EPOCH-R), which persisted on Cox regression (hazard ratio, 1.88; 95% confidence interval, 1.03-3.83; P 5 0.04). Furthermore, rituximab was associated with improved PFS on multivariable analyses (hazard ratio, 0.35; 95% confidence interval, 0.18-0.69; P 5 0.002). Collectively, GZL is a heterogeneous and likely more common entity and often with nonmediastinal presentation, whereas outcomes seem superior when treated with a rituximab-based, DLBCL-specific regimen.

Mediastinal gray zone lymphoma: clinico-pathological characteristics and outcomes of 99 patients from the Lymphoma Study Association

“…This lack of benefit might be related to the utilization of a dose-intensive regimen or to the lack of statistical power with a relatively low number of patients included in this retrospective cohort. These data differ from those previously reported 11 and may require further investigation. Radiotherapy for patients in CR did not seem to add any benefit in terms of EFS or OS; nevertheless, one patient in PR converted to CR thanks to mediastinal radiation.…”

“…The overall response rate was 80% in our report, including 73% CR, as compared to 71% ORR and 59% CR in the study by Evens et al 11 The 2-year estimated EFS in the present report is slightly higher than in Evens et al (63% vs. 40%), but the 2-year OS was similar in both reports (85% vs. 88%). The difference might be related to the first-line strategy with more dose-intensive regimen administered in our series.…”

“…6 Clinico-pathological characteristics of the 99 patients showed that patients were young, as previously reported, 2 but with a small female predominance, in contrast to other reports. 2,11,13 This difference might be related to the limited number of patients in each study. The majority of the cases had CHL-like morphology.…”

“…13 The largest previously reported series of GZL between diffuse large B-cell lymphoma (DLBCL) and CHL included 112 patients, 43% with a mediastinal GZL and 57% without mediastinal involvement. 11 At a 31-month median follow up, 2-year PFS and OS rates were 40% and 88%, respectively. Furthermore, they observed that rituximab combined with chemotherapy could improve patient prognosis.…”

“…[2][3][4][5] Although more recent publications defined a particular methylation profile for this entity, 6,7 and a particular immunohistochemistry scoring system to distinguish it from CHL and PMBCL, 8 there is a need for clarification of the clinico-pathological diagnostic criteria for MGZL. Previous retrospective studies 4,5,[9][10][11][12] (including from 2 to 112 cases) showed that patients with an MGZL had a poorer outcome than patients with a PMBCL or diffuse large B-cell lymphoma (DLBCL). The poor prognosis was confirmed by the prospective study of the National Cancer Institute that included 24 MGZL cases treated with rituximab and an intensified chemotherapy regimen (namely DA-EPOCH-R: dose adapted etoposide, prednisolone, oncovin, cyclophosphamide, doxorubicin) with a shorter progression-free survival (PFS) and overall survival (OS) as compared with PMBCL.…”