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.

Key Points• The median posttransformation survival of 5 years suggests improved outcomes for transformed FL in the modern era.• Five-year progression-free and overall survival (66% and 88%) are favorable for patients with evidence of transformation at diagnosis.We assessed the incidence, prognostic features, and outcomes associated with transformation of follicular lymphoma (FL) among 2652 evaluable patients prospectively enrolled in the National LymphoCare Study. At a median follow-up of 6. , 83-86). The median overall survival posttransformation was 5 years. Forty-seven patients with evidence of transformation at the time of diagnosis shared similar prognostic factors and survival rates to those without transformation. Improved outcomes for transformation in the modern era are suggested by this observational study. This trial is registered at www.clinicaltrials.gov as #NCT00097565. (Blood. 2015;126(7):851-857)

In the setting of contemporary practice with routine R use, stratifying patients into good, intermediate, and poor FLIPI risk groups predicts distinct outcomes in terms of OS and PFS. FLIPI remains an important prognostic index in the R era and should be used in clinical practices to support discussions about prognosis.

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To examine the effectiveness of an initial management strategy of watchful waiting for follicular lymphoma (FL) in clinical practice, we compared outcomes for patients diagnosed 2004-2007 in the United States initially managed with watchful waiting with outcomes following initial rituximab monotherapy and chemoimmunotherapy. In total, 1754 stage II-IV patients in the National LymphoCare Study underwent watchful waiting (n = 386), rituximab monotherapy (n = 296) or rituximab plus chemotherapy (n = 1072) as initial management strategy. Female patients and those who received treatment in the Northeast or in an academic setting more commonly underwent watchful waiting versus initial chemoimmunotherapy; whereas patients with grade 3 histology, anaemia, elevated lactate dehydrogenase, extranodal involvement, B symptoms or performance status ≥1 more commonly received chemoimmunotherapy. Although time to new treatment and progression-free survival following first- and second-line therapy were improved with chemoimmunotherapy, and time to chemotherapy was improved with rituximab monotherapy, there were no differences in overall survival between watchful waiting and chemoimmunotherapy or rituximab monotherapy. With 8-year overall survival estimates of 74%, initial management with watchful waiting in the context of sequential therapy remains a viable option for FL patients in the modern era. This trial was registered at www.clinicaltrials.gov (NCT00097565).

Summary Data from the National LymphoCare Study (a prospective, multicentre registry that enrolled follicular lymphoma (FL) patients from 2004–2007) were used to determine disease characteristics, treatment patterns, outcomes and prognosis for elderly FL (eFL) patients. Of 2650 FL patients, 209 (8%) were aged >80 years; these eFL patients more commonly had grade 3 disease, less frequently received chemoimmunotherapy and anthracyclines, and had lower response rates when compared to younger patients. With a median follow-up of 6.9 years, 5-year overall survival (OS) for eFL patients was 59%; 38% of deaths were lymphoma-related. No treatment produced superior OS among eFL patients. In multivariate Cox models, anaemia, B-symptoms and male sex predicted worse OS (P < 0·01); a prognostic index of these factors (0, 1 or ≥2 present) predicted OS (hazard ratio [95% confidence interval]: ≥2 vs. 0, 4·72 [2·38–9·33], ; 1 vs. 0, 2·63 [1·39–4·98]), with a higher concordance index (0·63) versus the Follicular Lymphoma International Prognostic Index (0·55). The index was validated in an independent cohort. In the largest prospective US-based eFL cohort, no optimal therapy was identified and nearly 40% of deaths were lymphoma-related, representing baseline outcomes in the modern era.

BACKGROUNDThe authors examined the “real-world” effectiveness of rituximab (R) maintenance therapy (R-maintenance) compared with observation after R-based induction therapy in patients with previously untreated follicular lymphoma (FL) in the United States.METHODSThe National LymphoCare Study is a prospective, multicenter, observational study that enrolled > 2700 untreated patients with FL diagnosed from 2004 to 2007 at 265 sites in the United States. Among these, patients who achieved at least stable disease after R-based induction therapy were eligible for the current analysis. Patients who initiated R-maintenance within 215 days of completing induction therapy were categorized as the R-maintenance group, and those who did not initiate therapy during this period were categorized as the observation group. The objective of the current study was to determine the effect of R-maintenance on progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS).RESULTSA total of 1439 patients completed R-based induction therapy, 1186 of whom met all inclusion criteria (541 patients received R-maintenance and 645 patients were observed). Characteristics that were found to be predictive of receiving R-maintenance were histology grade (1/2), Ann Arbor stage of disease (III/IV), geographic region (region other than the West), and practice setting (community practice). With a median follow-up of 5.7 years, R-maintenance was associated with superior PFS (hazards ratio [HR], 0.68; 95% confidence interval [95% CI], 0.56-0.84 [P = .0003]) and TTNT (HR, 0.66; 95% CI, 0.52-0.84 [P = .0007]). No significant difference in OS was observed (HR, 0.81; 95% CI, 0.58-1.14 [P = .23]).CONCLUSIONSR-maintenance in patients with FL and at least stable disease after R-based induction therapy provided significantly longer PFS and TTNT in comparison with observation, but no significant difference in OS was observed with 5-years of follow-up. This comparative effectiveness study aligns with the results of randomized trials suggesting that similar outcomes occur with R-maintenance in FL with the treatment variations observed in clinical practice. Cancer 2014;120:1830–1837. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.The authors present what, to their knowledge, is the largest published series to date of prospectively enrolled patients with previously untreated follicular lymphoma in the modern era examining the effectiveness of rituximab maintenance in clinical practice. With > 5 years of follow-up, it was found that, compared with observation, receipt of rituximab maintenance therapy was associated with significantly longer progression-free survival and time to next treatment in previously untreated patients with follicular lymphoma who achieved at least stable disease after rituximab-based induction therapy.

We aimed to comprehensively study sex differences in disease and patients’ characteristics, treatment and outcomes in patients with follicular lymphoma (FL) in the United States (USA) utilizing the National LymphoCare Study registry (2004–2014). Among evaluable males (n = 1277) and females (n = 1375) with FL, females less commonly received anthracyclines and were more likely to receive rituximab monotherapy. Overall response rates were comparable between sex groups. With a median follow-up of 8.1 years, male sex emerged as an adverse factor for PFS (HR, 0.84, 95% CI, 0.72–0.97). Lymphoma-related mortality (HR, 0.46; 0.23–0.93) and overall survival (HR, 0.63; 0.41–0.97) favored females aged ≤60 years. There are subtle differences in outcomes between male and female FL patients diagnosed and treated in the contemporary era. These data represent the largest prospective analysis of FL patients in the USA based on sex and can aid design of clinical trials for this disease.