Grade 3 Follicular Lymphoma: Outcomes in the Rituximab Era

Whether to clinically approach follicular lymphoma (FL) Grade 3 as an indolent or aggressive lymphoma, especially since the introduction of rituximab, is unclear. Our experience with FL Grade 3A, compared with FL Grade 3B or with concomitant diffuse large B cell lymphoma, primarily treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone suggests possible long-term remissions. This must be confirmed with longer follow-up and additional studies. Follicular lymphoma (FL) is heterogeneous. Although FL Grade 3B (FL3B) is treated as aggressive FL (aggFL), an optimal approach to FL Grade 3A (FL3A) remains unclear because few data exist on clinical outcomes on the basis of subclassification of FL Grade 3 (FL3) since the introduction of rituximab. We report outcomes of FL3 in the rituximab era. We identified and analyzed a retrospective cohort of 53 patients with FL3A, 3B, and FL Grade 3 with areas of diffuse large B-cell lymphoma (DLBCL). They were divided into 2 groups: aggFL (n = 21) included patients with FL3B (n = 10) and FL3 (A or B) with concomitant DLBCL (n = 11); indolent lymphoma (n = 32) included only FL3A. Baseline characteristics did not differ between the groups. rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) was initial treatment in 15 (79%) of patients with aggFL and 21 (72%) of those with FL3A; rituximab was included in initial therapy in 18 (95%) and 24 (83%), respectively. Comparing aggFL and FL3A, 5-year overall survival was 90% versus 79% (P = .97) and 5-year progression-free survival (PFS) 44% versus 34% (P = .75), respectively. We conclude that outcomes for FL3, primarily treated with R-CHOP, do not differ between FL3A and aggFL (FL3B and FL3/DLBCL). The aggFL group showed a plateau in PFS confirming these should be treated with curative intent. FL3A patients, mainly managed with R-CHOP, also show an apparent plateau in PFS. Although longer follow-up and confirmation in other data sets is required, this indicates potential undertreatment of FL3A with less aggressive regimens often used for indolent lymphoma.