Outcomes following watchful waiting for stage II–IV follicular lymphoma patients in the modern era

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).

[1]  J. Friedberg,et al.  Outcomes of transformed follicular lymphoma in the modern era: a report from the National LymphoCare Study (NLCS). , 2015, Blood.

[2]  J. Cerhan,et al.  Comparison of the effectiveness of frontline chemoimmunotherapy regimens for follicular lymphoma used in the United States , 2015, Leukemia & lymphoma.

[3]  M. Bøgsted,et al.  A population‐based study of prognosis in advanced stage follicular lymphoma managed by watch and wait , 2015, British journal of haematology.

[4]  R. Advani,et al.  Anxiety and health-related quality of life among patients with low-tumor burden non-Hodgkin lymphoma randomly assigned to two different rituximab dosing regimens: results from ECOG trial E4402 (RESORT). , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  R. Gascoyne,et al.  Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: eastern cooperative oncology group protocol e4402. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  R. Stephens,et al.  Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. , 2014, The Lancet. Oncology.

[7]  R. Houot,et al.  Long-term follow up of the FL2000 study comparing CHVP-interferon to CHVP-interferon plus rituximab in follicular lymphoma , 2013, Haematologica.

[8]  R. Gascoyne,et al.  Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  J. Cerhan,et al.  Follicular lymphoma in the United States: first report of the national LymphoCare study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  T. Ittel,et al.  Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  N. Schmitz,et al.  Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of t , 2005, Blood.

[12]  R. Marcus,et al.  CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. , 2005, Blood.

[13]  K. Maclennan,et al.  Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial , 2003, The Lancet.

[14]  R. D'Agostino Adjustment Methods: Propensity Score Methods for Bias Reduction in the Comparison of a Treatment to a Non‐Randomized Control Group , 2005 .

[15]  B. Nathwani,et al.  A clinical evaluation of the International Lymphoma Study Group Classification of non-Hodgkin's lymphoma: a report of the Non-Hodgkin's Lymphoma Classification Project , 1997 .

[16]  H. Tilly,et al.  Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  E. Jaffe,et al.  The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. , 1988, Seminars in hematology.

[18]  T. Lister,et al.  Follicular lymphoma: prognostic factors for response and survival. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  S. Horning,et al.  Female Reproductive Potential after Treatment for Hodgkin's Disease , 1981, The New England journal of medicine.

[20]  S. Rosenberg,et al.  No initial therapy for stage III and IV non-Hodgkin's lymphomas of favorable histologic types. , 1979, Annals of internal medicine.