Introduction: Follicular lymphoma(FL) is a heterogeneous lymphoid malignancy that can be further sub classified into grades 1, 2, 3A and 3B, based on the percentage of centroblasts per high power field. Historically, grade 3A FL has been considered to have a biological and clinical profile akin to grades 1-2 FL whereas grade 3B FL is considered to have a clinical presentation and treatment outcome similar to diffuse large B cell lymphoma (DLBCL). We examine the impact of FL grading and sub classification on initial treatment choice and outcomes in a cohort of FL subjects diagnosed in the rituximab era.
Methods: We accessed the Hematological Malignancies database of University Hospitals Seidman Cancer Center to retrieve data on FL patients (pts) diagnosed between 2002 and 2014. Demographic data, laboratory and disease characteristics were recorded. We excluded pts with incomplete follow up data and any unclassified FL cases. Biopsies from all available grade 3 FL cases were reviewed by a hematopathologist for sub classification into grade 3A or 3B FL categories. The outcomes of grade 3 FL patient cohort were separately compared with contemporaneous cohorts of patients diagnosed with grade 1-2 FL and germinal center B cell (GCB) subtype of DLBCL. The Kaplan-Meier method was used to assess overall survival (OS) and progression-free survival (PFS). Two-tailed log-rank test compared OS and PFS curves. All analyses were performed using IBM SPSS Statistics 2015.
Results: We identified 227 FL pts with complete clinical information. Approximately one third of pts (n=62, 27%) had grade 3 FL (grade 3A, n = 35, grade 3B, n = 24; unclassified, n = 2). Comparisons between baseline characteristics and initial therapy of grade 1-2 FL and grade 3 FL are presented in Table 1. While baseline demographic characteristics were not different, the rate of transformation was higher in grade 3 FL. Use of cytotoxic chemo-immunotherapy and anthracycline was more common in grade 3 FL.
Median OS was not reached for the whole FL cohort. We did not observe a statistically significant difference in OS between grade 1-2 FL and grade 3 FL. Grade 3 FL presented a higher PFS compared with grade 1-2 FL (5-year PFS 61% vs 41%, p=0.016) (Figure 1). To examine the effect of histologic grade on outcomes after therapy, we limited the analysis to subjects treated with chemo-immunotherapy as initial treatment: 5 year PFS was longer for patients diagnosed with grade 3 FL (61% vs 43 %, p=0.015). Limiting the analysis to subjects treated only with first line anthracycline-containing chemo-immunotherapy also demonstrated grade 3 FL presenting with a longer PFS (5-year PFS 61 % vs 31 %, p<0.001). Further subgroup analysis comparing only grade 3A FL (n=35) pts with the anthracycline treated grade 1-2 FL (n=57) demonstrated longer 5-year PFS in the grade 3A cohort (p<0.001). (Figure 2). Consistent with previous reports, there were no differences in baseline clinical features, PFS or OS between the grade 3A and grade 3B FL patient cohorts. Further comparison of outcomes of grade 3A FL in our cohort had a similar PFS to GCB DLBCL (5 year PFS 62% vs 56 %, p=0.188).
Conclusion: In this retrospective study of outcomes of follicular lymphoma in the rituximab era, we observed that patients diagnosed with grade 3 FL have better PFS than patients diagnosed with lower grade FL. This improved outcome appears to be independent of the choice of initial therapy, with an apparent plateau in the risk of relapse of patients diagnosed with grade 3A FL, suggesting a subgroup of these subjects can receive front line treatment with curative intent.
Malek: Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau. Cooper: Novartis: Research Funding. de Lima: Pfizer: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Research Funding. Caimi: Abbvie: Equity Ownership; Seattle Genetics: Equity Ownership; Incyte: Equity Ownership; Celgene: Speakers Bureau.
Asterisk with author names denotes non-ASH members.