Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study

Abstract

A B S T R A C T PurposeTwenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death. Patients and MethodsIn total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility. ResultsOf 588 patients, 19% (n ϭ 110) had early POD, 71% (n ϭ 420) were in the reference group, 8% (n ϭ 46) were lost to follow-up, and 2% (n ϭ 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index-adjusted hazard ratio, 19.8). ConclusionIn patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials.

The role of autologous and allogeneic stem cell transplantation in the management of indolent B-cell lymphoma

“…[70][71][72] A recent report from the National LymphoCare Study reports that patients who relapse within 2 years of completing treatment with R-CHOP have an inferior 5-year OS (50% vs 90%). 73 A pragmatic approach to SCT was suggested by the EBMT in their consensus document. 74 ASCT was suggested at first relapse in patients with a short first remission (or with a high-risk FLIPI score) or in subsequent chemotherapy-sensitive relapses.…”

Prognostic relevance of CD163 and CD8 combined with EZH2 and gain of chromosome 18 in follicular lymphoma: a study by the Lunenburg Lymphoma Biomarker Consortium

“…32 The objective of the study herein by the LLBC consortium was to critically assess, in a homogeneously treated patient cohort, whether the previously implicated microenvironmental and molecular markers of the tumor have clinically relevant prognostic value. We hypothesized that the microenvironmental and molecular markers would be most prominent when we compared tissue samples of patients with an extremely poor prognosis (i.e., progression or death within 2 years, a well-established criterion for poor prognosis in FL) 33 with those with a very favorable prognosis (a response to first-line treatment lasting >5 years). The LLBC gene panel incorporated the molecular markers which were frequently mutated, and were at that time published, as well as markers that were rarely mutated such as FAS and MYD88, [28][29][30] since with our study design we hypothesized the ability to also reveal the prognostic value of rare mutations.…”

Efficacy and safety of idelalisib in patients with relapsed, rituximab- and alkylating agent-refractory follicular lymphoma: a subgroup analysis of a phase 2 study

“…Andreas Viardot, 5 Kristie A. Blum, 6 Christopher R. Flowers, 7 Wojciech J. Jurczak, 8 Ian W. Flinn, 9 Brad S. Kahl,10 Peter Martin, 11 Yeonhee Kim, 12 Sanatan Shreay, 12 Matthias Will, 13 Bess Sorensen, 13 Madlaina Breuleux, 13 Pier Luigi Zinzani 14 …”