Comparing the cost-effectiveness of rituximab maintenance and radioimmunotherapy consolidation versus observation following first-line therapy in patients with follicular lymphoma.

BACKGROUND Phase 3 randomized trials have shown that maintenance rituximab (MR) therapy or radioimmunotherapy (RIT) consolidation following frontline therapy can improve progression-free survival for patients with follicular lymphoma (FL), but the cost-effectiveness of these approaches with respect to observation has not been examined using a common modeling framework. OBJECTIVES To evaluate and compare the economic impact of MR and RIT consolidation versus observation, respectively, following the first-line induction therapy for patients with advanced-stage FL. METHODS We developed Markov models to estimate patients' lifetime costs, quality-adjusted life-years (QALYs), and life-years (LYs) after MR, RIT, and observation following frontline FL treatment from the US payer's perspective. Progression risks, adverse event probabilities, costs, and utilities were estimated from clinical data of Primary RItuximab and MAintenance (PRIMA) trial, Eastern Cooperative Oncology Group (ECOG) trial (for MR), and First-line Indolent Trial (for RIT) and the published literature. We evaluated the incremental cost-effectiveness ratio for direct comparisons between MR/RIT and observation. Model robustness was addressed by one-way and probabilistic sensitivity analyses. RESULTS Compared with observation, MR provided an additional 1.089 QALYs (1.099 LYs) and 1.399 QALYs (1.391 LYs) on the basis of the PRIMA trial and the ECOG trial, respectively, and RIT provided an additional 1.026 QALYs (1.034 LYs). The incremental cost per QALY gained was $40,335 (PRIMA) or $37,412 (ECOG) for MR and $40,851 for RIT. MR and RIT had comparable incremental QALYs before first progression, whereas RIT had higher incremental costs of adverse events due to higher incidences of cytopenias. CONCLUSIONS MR and RIT following frontline FL therapy demonstrated favorable and similar cost-effectiveness profiles. The model results should be interpreted within the specific clinical settings of each trial. Selection of MR, RIT, or observation should be based on patient characteristics and expected trade-offs for these alternatives.

[1]  R. Pettengell,et al.  PCN62 UTILITY ELICITATION IN PATIENTS WITH FOLLICULAR LYMPHOMA , 2006 .

[2]  George A. Wells,et al.  An Assessment of Methods to Combine Published Survival Curves , 2000, Medical decision making : an international journal of the Society for Medical Decision Making.

[3]  E. Arias United States life tables, 2007. , 2011, National vital statistics reports : from the Centers for Disease Control and Prevention, National Center for Health Statistics, National Vital Statistics System.

[4]  Christopher R Flowers,et al.  Practical approach for using Medicare data to estimate costs for cost–effectiveness analysis , 2005, Expert review of pharmacoeconomics & outcomes research.

[5]  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.

[6]  J. Leonard,et al.  Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  S. Horning,et al.  Follicular lymphoma: clinical features and treatment. , 2008, Hematology/oncology clinics of North America.

[8]  M. Kaminski,et al.  Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus (131)iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  J R Beck,et al.  Markov Models in Medical Decision Making , 1993, Medical decision making : an international journal of the Society for Medical Decision Making.

[10]  Jonathan Karnon,et al.  Model Parameter Estimation and Uncertainty Analysis , 2012, Medical decision making : an international journal of the Society for Medical Decision Making.

[11]  M. Drummond,et al.  Health Care Technology: Effectiveness, Efficiency and Public Policy@@@Methods for the Economic Evaluation of Health Care Programmes , 1988 .

[12]  D. Lubeck,et al.  Economic evaluation of rituximab plus cyclophosphamide, vincristine and prednisolone for advanced follicular lymphoma , 2008, Leukemia & lymphoma.

[13]  A. Hagenbeek,et al.  Health-Related Quality of Life in Patients with Advanced-Stage Follicular Lymphoma Receiving Consolidation with 90Y-Ibritumomab Tiuxetan (Zevalin®) of First Remission: Results from the Randomized Phase 3 First-Line Indolent Trial (FIT). , 2007 .

[14]  J. Hornberger,et al.  Cost-effectiveness of rituximab as maintenance therapy in patients with follicular non-Hodgkin lymphoma after responding to first-line rituximab plus chemotherapy , 2012, Leukemia & lymphoma.

[15]  M. Kaminski,et al.  Cyclophosphamide, vincristine, and prednisone followed by tositumomab and iodine-131-tositumomab in patients with untreated low-grade follicular lymphoma: eight-year follow-up of a multicenter phase II study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  T. Illidge Radioimmunotherapy of lymphoma: a treatment approach ahead of its time or past its sell-by date? , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  J. Vose,et al.  Initial therapeutic strategy in follicular lymphoma (FL): An analysis from the National LymphoCare Study (NLCS). , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  D. Issa,et al.  Cost‐effectiveness of rituximab as maintenance treatment for relapsed follicular lymphoma: results of a population‐based study , 2014, European journal of haematology.

[19]  A. Hagenbeek,et al.  90Yttrium-ibritumomab tiuxetan consolidation of first remission in advanced-stage follicular non-Hodgkin lymphoma: updated results after a median follow-up of 7.3 years from the International, Randomized, Phase III First-LineIndolent trial. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  R. Fisher,et al.  Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  M. Kersten,et al.  Treatment strategies in advanced stage follicular lymphoma. , 2011, Best practice & research. Clinical haematology.

[22]  B. Cheson New response criteria for lymphomas in clinical trials. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[23]  A. Hagenbeek,et al.  Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  S. Swerdlow,et al.  Phase II Trial of Short-Course CHOP-R Followed by 90Y-ibritumomab Tiuxetan and Extended Rituximab in Previously Untreated Follicular Lymphoma , 2008, Clinical Cancer Research.

[25]  D. Abbey,et al.  Medicare Physician Fee Schedule. , 2023, JAMA.

[26]  Mark Stevenson,et al.  Rituximab for the first-line treatment of stage III-IV follicular lymphoma (review of Technology Appraisal No. 110): a systematic review and economic evaluation. , 2012, Health technology assessment.

[27]  A. Hagenbeek,et al.  Rituximab maintenance versus radio-immunotherapy consolidation in first remission follicular non-Hodgkin lymphoma. , 2013, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[28]  Max Wolf,et al.  Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. , 2006, Blood.

[29]  J. Armitage,et al.  A decade of progress in lymphoma: advances and continuing challenges. , 2010, Clinical lymphoma, myeloma & leukemia.

[30]  L. Gordon,et al.  Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  A. Freedman,et al.  Follicular lymphoma: 2012 update on diagnosis and management , 2012, American journal of hematology.

[32]  J. Hainsworth,et al.  Rituximab plus short-duration chemotherapy followed by Yttrium-90 Ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. , 2009, Clinical lymphoma & myeloma.

[33]  R. Marcus,et al.  An evaluation of the cost-effectiveness of rituximab in combination with chemotherapy for the first-line treatment of follicular non-Hodgkin's lymphoma in the UK. , 2010, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[34]  K. Fairman,et al.  What Is the Price Benchmark to Replace Average Wholesale Price (AWP)? , 2010, Journal of managed care pharmacy : JMCP.

[35]  Andrew Lister,et al.  Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial , 2011, The Lancet.

[36]  R. Advani,et al.  ACR Appropriateness Criteria: Localized nodal indolent lymphoma. , 2013, Oncology.

[37]  E. Deconinck,et al.  Cost Effectiveness of Rituximab Maintenance Therapy in Follicular Lymphoma , 2010, PharmacoEconomics.

[38]  S. Dewilde,et al.  Bendamustine-rituximab: a cost-utility analysis in first-line treatment of indolent non-Hodgkin’s lymphoma in England and Wales , 2014, Journal of medical economics.

[39]  S. Pileri,et al.  Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ). , 2008, The Lancet. Oncology.

[40]  S. Swerdlow WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues , 2017 .

[41]  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 .

[42]  A. Ng,et al.  Cost-Effectiveness Analysis of Computerized Tomography in the Routine Follow-Up of Patients After Primary Treatment for Hodgkin's Disease , 2007 .

[43]  J. Martikainen,et al.  Economic evaluation of sequential treatments for follicular non-hodgkin lymphoma. , 2012, Clinical therapeutics.

[44]  M. Hansmann,et al.  Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  J. Cerhan,et al.  The use and effectiveness of rituximab maintenance in patients with follicular lymphoma diagnosed between 2004 and 2007 in the United States , 2014, Cancer.