Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Cost-effectiveness analysis of allogeneic versus autologous stem cell transplant versus chemo-immunotherapy for early relapse of follicular lymphoma within 2 years of initial therapy

Abstract

This study compared the quality-adjusted effectiveness and costs of three treatment options for transplant-eligible patients with early progression (POD24) of follicular lymphoma. A Markov decision-analytic model using a 20-year time horizon was used to compare allogeneic stem cell transplant (alloSCT), autologous stem cell transplant (ASCT), and chemo-immunotherapy (O-CHOP). For second relapse/refractory disease, novel therapy use was modeled, including lenalidomide and rituximab/obinutuzumab, and PI3K inhibitors (PI3Ki). Costs were considered from a Canadian public health payer’s perspective. Probabilistic analyses (10,000 simulations) demonstrated that at a willingness-to-pay threshold of $50,000, ASCT was most cost effective 60% of the time. ASCT resulted in more life years (10.2 vs. alloSCT 9.9 vs. O-CHOP 10.0) and quality-adjusted life years (7.5 vs. alloSCT 6.6 vs. O-CHOP 7.4), with the lowest direct costs ($190,128 CAD). In sensitivity analyses, the model was robust to key variables, including differing probabilities of progression, non-relapse mortality, graft-versus-host-disease (GVHD), costs of treating GVHD, costs of PI3Ki, and probability of secondary malignancy from ASCT. However, if patients were older than 65 years or their life expectancy was less than 10 years, chemo-immunotherapy was the preferred strategy. When considering cost, effectiveness, and toxicities, the preferred treatment strategy for most patients with POD24 follicular lymphoma is ASCT.

This is a preview of subscription content, access via your institution

Access options

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Simplified Markov decision analysis model.
Fig. 2: Cost-effectiveness acceptability curve.
Fig. 3

Similar content being viewed by others

References

  1. Luminari S, Bellei M, Biasoli I, Federico M. Follicular lymphoma - treatment and prognostic factors. Rev Bras Hematol Hemoter. 2012;34:54–9.

    Article  Google Scholar 

  2. Junlen HR, Peterson S, Kimby E, Lockmer S, Linden O, Nilsson-Ehle H, et al. Follicular lymphoma in Sweden: nationwide improved survival in the rituximab era, particularly in elderly women: a Swedish Lymphoma Registry study. Leukemia. 2015;29:668–76.

    Article  CAS  Google Scholar 

  3. Casulo C, Byrtek M, Dawson KL, Zhou X, Farber CM, Flowers CR, et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the National LymphoCare Study. J Clin Oncol. 2015;33:2516–22.

    Article  CAS  Google Scholar 

  4. Jurinovic V, Kridel R, Staiger AM, Szczepanowski M, Horn H, Dreyling MH, et al. Clinicogenetic risk models predict early progression of follicular lymphoma after first-line immunochemotherapy. Blood. 2016;128:1112–20.

    Article  CAS  Google Scholar 

  5. Maurer MJ, Bachy E, Ghesquieres H, Ansell SM, Nowakowski GS, Thompson CA, et al. Early event status informs subsequent outcome in newly diagnosed follicular lymphoma. Am J Hematol. 2016;91:1096–101.

    Article  Google Scholar 

  6. Seymour JF, Marcus R, Davies A, Gallop-Evans E, Grigg A, Haynes A, et al. Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression. Haematologica. 2020;105:1465.

    Article  Google Scholar 

  7. Lansigan F, Barak I, Pitcher B, Jung SH, Cheson BD, Czuczman M, et al. The prognostic significance of PFS24 in follicular lymphoma following firstline immunotherapy: a combined analysis of 3 CALGB trials. Cancer Med. 2019;8:165–73.

    Article  CAS  Google Scholar 

  8. Freeman CL, Kridel R, Moccia AA, Savage KJ, Villa DR, Scott DW, et al. Early progression after bendamustine-rituximab is associated with high risk of transformation in advanced stage follicular lymphoma. Blood. 2019;134:761–4.

    Article  CAS  Google Scholar 

  9. Evens AM, Vanderplas A, LaCasce AS, Crosby AL, Nademanee AP, Kaminski MS, et al. Stem cell transplantation for follicular lymphoma relapsed/refractory after prior rituximab: a comprehensive analysis from the NCCN lymphoma outcomes project. Cancer. 2013;119:3662–71.

    Article  CAS  Google Scholar 

  10. Smith SM, Godfrey J, Ahn KW, DiGilio A, Ahmed S, Agrawal V, et al. Autologous transplantation versus allogeneic transplantation in patients with follicular lymphoma experiencing early treatment failure. Cancer. 2018;124:2541–51.

    Article  CAS  Google Scholar 

  11. Jimenez-Ubieto A, Grande C, Caballero D, Yanez L, Hernandez-Garcia MT, Novelli S, et al. Secondary malignancies and survival outcomes after autologous stem cell transplantation for follicular lymphoma in the pre-rituximab and rituximab eras: a long-term follow-up analysis from the Spanish GELTAMO registry. Bone Marrow Transplant. 2018;53:780–3.

    Article  CAS  Google Scholar 

  12. Manna M, Lee-Ying R, Davies G, Stewart C, Oh DH, Peters A, et al. Autologous transplantation improves survival rates for follicular lymphoma patients who relapse within two years of chemoimmunotherapy: a multi-center retrospective analysis of consecutively treated patients in the real world. Leuk Lymphoma. 2019;60:133–41.

    Article  Google Scholar 

  13. Sehn LHTM, Bouabdallah K, Dueck G, Gribben JG, Lugtenburg PJ, Salles GA, et al. Sustained overall survival benefit of obinutuzumab plus bendamustine followed by obinutuzumab maintenance compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma: final results of the Gadolin Study. Blood. 2019;134:2822.

    Article  Google Scholar 

  14. Jimenez-Ubieto A, Grande C, Caballero D, Yanez L, Novelli S, Hernandez-Garcia MT, et al. Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure who reach complete response after rescue treatment. Hematol Oncol. 2018;36:765–72.

    Article  Google Scholar 

  15. Casulo C, Barr PM. How I treat early-relapsing follicular lymphoma. Blood. 2019;133:1540–7.

    Article  CAS  Google Scholar 

  16. StatisticsCanada. Table 13-10-0710-01 Deaths and mortality rates, by age group. https://doi.org/10.25318/1310071001-eng.

  17. Bank-of-Canada. Inflation Calculator. 2020. https://www.bankofcanada.ca/rates/related/inflation-calculator/.

  18. Sehn LH, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K, et al. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016;17:1081–93.

    Article  CAS  Google Scholar 

  19. Kliman D, Nivison-Smith I, Gottlieb D, Hamad N, Kerridge I, Purtill D, et al. Hematopoietic stem cell transplant recipients surviving at least 2 years from transplant have survival rates approaching population levels in the modern era of transplantation. Biol Blood Marrow Transplant. 2020;26:1711–8.

    Article  Google Scholar 

  20. Flinn IW, Miller CB, Ardeshna KM, Tetreault S, Assouline SE, Mayer J, et al. DYNAMO: a phase II study of duvelisib (IPI-145) in patients with refractory indolent non-Hodgkin lymphoma. J Clin Oncol. 2019;37:912–22.

    Article  CAS  Google Scholar 

  21. Dreyling M, Santoro A, Mollica L, Leppa S, Follows G, Lenz G, et al. Long-term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2-year follow-up of the CHRONOS-1 study. Am J Hematol. 2020;95:362–71.

    Article  CAS  Google Scholar 

  22. Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, et al. AUGMENT: a Phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019;37:1188–99.

    Article  Google Scholar 

  23. Andorsky DJCM, Yacoub A, Melear JM, Fanning SR, Kolibaba K, Lansigan F, et al. MAGNIFY: Phase IIIb interim analysis of induction R2 followed by maintenance in relapsed/refractory indolent non-Hodgkin lymphoma. J Clin Oncol. 2019;37:7513.

    Article  Google Scholar 

  24. Morschhauser F, Le Gouill S, Feugier P, Bailly S, Nicolas-Virelizier E, Bijou F, et al. Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study. Lancet Haematol. 2019;6:e429–e37.

    Article  Google Scholar 

  25. Granfeldt Ostgard LS, Medeiros BC, Sengelov H, Norgaard M, Andersen MK, Dufva IH, et al. Epidemiology and clinical significance of secondary and therapy-related acute myeloid leukemia: a National Population-Based Cohort Study. J Clin Oncol. 2015;33:3641–9.

    Article  Google Scholar 

  26. Lee KMMC, Bryan S, Coyle D, Krahn M, McCabe C. Guidelines for the economic evaluation of health technologies. Canada: Canadian Agency for Drugs and Technologies in Health; 2017.

  27. Hirayama AV, Gauthier J, Hay KA, Voutsinas JM, Wu Q, Pender BS, et al. High rate of durable complete remission in follicular lymphoma after CD19 CAR-T cell immunotherapy. Blood. 2019;134:636–40.

    Article  CAS  Google Scholar 

  28. D’Souza A FC. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR summary slides, 2019. 2019. http://www.cibmtr.org.

  29. Cheson BD, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K, et al. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. J Clin Oncol. 2018;36:2259–66.

    Article  CAS  Google Scholar 

  30. Casulo C, Friedberg JW, Ahn KW, Flowers C, DiGilio A, Smith SM, et al. Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis. Biol Blood Marrow Transplant. 2018;24:1163–71.

    Article  Google Scholar 

  31. Sabloff M, Atkins HL, Bence-Bruckler I, Bredeson C, Fergusson D, Genest P, et al. A 15-year analysis of early and late autologous hematopoietic stem cell transplant in relapsed, aggressive, transformed, and nontransformed follicular lymphoma. Biol Blood Marrow Transplant. 2007;13:956–64.

    Article  Google Scholar 

  32. Jimenez-Ubieto A, Grande C, Caballero D, Yáñez L, Novelli S, Hernández MT, et al. Progression-free survival at 2 years post-autologous transplant: a surrogate end point for overall survival in follicular lymphoma. Cancer Med. 2017;6:2766–74.

    Article  CAS  Google Scholar 

  33. Jimenez-Ubieto A, Grande C, Caballero D, Yáñez L, Novelli S, Hernández-Garcia MT, et al. Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure without the need for immunotherapy. Hematol Oncol Stem Cell Ther. 2019;12:194–203.

    Article  CAS  Google Scholar 

  34. Jurinovic V, Metzner B, Pfreundschuh M, Schmitz N, Wandt H, Keller U, et al. Autologous Stem Cell Transplantation for Patients with Early Progression of Follicular Lymphoma: A Follow-Up Study of 2 Randomized Trials from the German Low Grade Lymphoma Study Group. Biol Blood Marrow Transplant. 2018;24:1172–9.

    Article  Google Scholar 

  35. van Oers MH, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, et al. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin’s lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol. 2010;28:2853–8.

    Article  CAS  Google Scholar 

  36. Csanadi M, Agh T, Tordai A, Webb T, Jeyakumaran D, Sengupta N, et al. A systematic literature review of incidence, mortality, and relapse of patients diagnosed with chronic graft versus host disease. Expert Rev Hematol. 2019;12:311–23.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the University of Toronto Postgraduate Medicine Research Award (Joseph M. West Memorial Fund).

Author information

Authors and Affiliations

Authors

Contributions

AV: data curation, formal analysis, funding acquisition, writing—original draft; JK: writing—review and editing; AP: conceptualization, funding acquisition, supervision, writing—review and editing.

Corresponding author

Correspondence to Anca Prica.

Ethics declarations

Conflict of interest

AV: No relevant disclosures; JK: BMS: Consultancy, Honoraria; Abbvie: Consultancy; Leukemia and Lymphoma Society Canada: Research Funding; Seattle Genetics: Consultancy, Honoraria; Amgen: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Princess Margaret Cancer Foundation: Research Funding; Gilead: Consultancy, Honoraria; Lundbeck: Honoraria; Roche: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria; AP: Astra Zeneca: Honoraria, Advisory Board; Gilead: Honoraria, Advisory Board.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vijenthira, A., Kuruvilla, J. & Prica, A. Cost-effectiveness analysis of allogeneic versus autologous stem cell transplant versus chemo-immunotherapy for early relapse of follicular lymphoma within 2 years of initial therapy. Bone Marrow Transplant 56, 2400–2409 (2021). https://doi.org/10.1038/s41409-021-01327-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41409-021-01327-5

This article is cited by

Search

Quick links