Early stage follicular lymphoma: what is the clinical impact of the first-line treatment strategy?

Abstract

BackgroundLess than 20% of patients with follicular lymphoma (FL) present with Ann Arbor Stage I or II disease at diagnosis. Numerous therapeutic options exist, however radiation therapy is considered the standard of care for early-stage disease based on single-institution or retrospective series. Our aim was to revisit the outcome of patients with localized FL in the rituximab era.Patients and MethodsWe analyzed the characteristics and outcomes of 145 early-stage FL patients, who were retrospectively divided into six groups according to their initial treatment: watchful waiting (WW), chemotherapy alone (CT), radiotherapy alone (RT), combined radiotherapy and chemotherapy (RT-CT), rituximab alone (Ri), and immunochemotherapy (Ri-CT).ResultsOf the 145 patients, 84 (57.9%) had stage I disease and 61 (42.1%) stage II. The complete response (CR) rate varied from 57% for the Ri group to 95% for the RT-CT group. Overall survival (OS) at 7.5 y of patients treated after 2000 was better than that of those treated prior to 2000. OS did not significantly differ from one treatment to another. In contrast, a significant difference was found for progression-free survival (PFS) at 7.5 y, which favored Ri-CT (60%) therapy versus the others (p=0.00135).ConclusionDelayed therapy initiation was associated with a similar OS than that observed in patients receiving immediate intervention. The “watchful waiting” strategy may thus be proposed as first-line therapy, similar to stage III and IV FL patients with a low tumor burden. However, when treatment is required, immunochemotherapy appears to be the best option.

A Canadian Evidence-Based Guideline for the First-Line Treatment of Follicular Lymphoma: Joint Consensus of the Lymphoma Canada Scientific Advisory Board

“…Another recent retrospective study divided patients into 6 groups according to their initial treatment: observation, RT alone, chemotherapy, RT with chemotherapy, rituximab monotherapy, and chemoimmunotherapy. 26 Similar to the findings of the LymphoCare database analysis, OS did not differ between treatments at 7.5 years, whereas PFS at 7.5 years was significantly higher with chemoimmunotherapy versus all other treatments (P ¼ .00135). 26 Accordingly, although these studies challenge the use of RT alone as the standard of care for localized FL, they are limited by their retrospective design and small numbers of patients.…”

“…[25][26][27][28][29][30][31][32][33][34][35] In identified studies, the median age of patients with localized FL generally ranged from 50 to 64 years. Although a few studies reported that age was an independent prognostic factor for outcome, with younger age being NG CR: 80.9% PR: 9.5% SD: 0% PD: 9.5% (All data for RT alone) Abbreviations: BCCA ¼ British Columbia Cancer Agency; BNLI ¼ British National Lymphoma Investigation; CLI ¼ central lymphatic irradiation; CR ¼ complete response/remission; CSS ¼ cause-specific survival; CT ¼ chemotherapy; DFS ¼ disease-free survival; DSS ¼ disease-specific survival; EFRT ¼ extended field radiotherapy; EFS ¼ event-free survival; FFLP ¼ freedom from local progression; FFP ¼ freedom from progression; FFTF ¼ freedom from treatment failure; FL ¼ follicular lymphoma; IFRT ¼ involved field radiotherapy; INRT ( 5 cm) ¼ involved node radiotherapy (with margins up to 5 cm); IRRT ¼ involved regional radiotherapy; NCRI ¼ National Cancer Research Institute; NG ¼ not given; NHL ¼ non-Hodgkin lymphoma; NS ¼ not significant; ORR ¼ overall response rate; OS ¼ overall survival; PD ¼ progressive disease; PFS ¼ progression-free survival; PR ¼ partial response/remission; RFS ¼ relapse-free survival; RR ¼ response rate; RT ¼ radiation therapy; SD ¼ stable disease; SEER ¼ Surveillance Epidemiology and End Results; STLI ¼ subtotal lymphoid irradiation; TBI ¼ total body irradiation; TLI ¼ total lymphoid irradiation; TNI ¼ total nodal irradiation.…”

“…[25][26][27] Treatment of localized FL remains poorly defined and controversial because of a lack of randomized phase III trials in this uncommon subpopulation. Accordingly, based on data from retrospective series, radiotherapy (RT) is considered the standard of care for localized FL by North American and European guidelines, as well as provincial guidelines in Canada.…”

Nature and importance of follicular lymphoma precursors

“…Considering the indolent clinical course, it is reasonable to assume that a fraction of such E. Mamessier et al 806 haematologica | 2014; 99(5) patients remain undiagnosed, potentially for many years. Based on trials showing no benefit of immediate chemotherapy in patients with a low tumor burden, 73,74 current guidelines recommend a WW approach, deferring treatment initiation until worsening of disease and/or clinical symptoms appear. 75 Most patients with a low tumor burden under WW have an improved quality of life for an average period of 2.5 years by delaying exposure to the toxic side-effects of chemotherapy, the reduced number of hospital visits and related interventions (therapeutic agents administration, blood puncture, etc.).…”

Clinical management and outcomes of completely resected stage I follicular lymphoma

“…5,6 Moreover, irradiation is the only treatment strategy to demonstrate any advantage in terms of overall survival, although the evidence for this was obtained from retrospective studies. 7,8 However, the reality is that several treatment strategies have been applied for patients with early-stage FL, including combined-modality therapy (CMT), irradiation alone, watch-and-wait (WW), and more recently, rituximab (R)-containing chemotherapy or R monotherapy, [9][10][11] probably because recommendations have been based on relatively small, retrospective studies from a single center. 5,6 Diseasefree survival rates for patients with early-stage disease were Clinical management and outcomes of completely resected stage I follicular lymphoma Norifumi Tsukamoto 9) 44 -54% at 10 years when treated with involved-field irradiation.…”