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Results of R-ESHAP as salvage therapy in refractory/relapsed follicular lymphoma: a real-world experience on behalf of GELCAB group

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Abstract

There is no standard treatment for relapsed follicular lymphoma (FL). Although platinum-based combinations are one of the most used treatments, few data have been reported in this setting. Our aim was to analyse R-ESHAP efficacy in relapsed FL patients. We retrospectively analysed 80 FL patients treated with R-ESHAP in the first or successive relapses. Responding patients received a stem cell transplantation following R-ESHAP. Seventeen histologically transformed patients were included. Median age was 50 years. At R-ESHAP initiation, 85% of the patients were in an advanced stage, 28% had a bulky disease and 40% had increased LDH. There were no statistically significant differences between POD24 and non-POD24 patients in terms of response to R-ESHAP (ORR 72% vs. 93%, p = 0.109). When analyzing R-ESHAP efficacy according to the response to the immediately previous line, patients achieving CR or PR had better CR rates to R-ESHAP than those who did not respond (CR of 57% vs. 15%, respectively, p = 0.009), as well as differences in OS (7.2 vs. 1.4 years, p < 0.0001) and in PFS (2.1 vs. 0.3 years, p < 0.0001). R-ESHAP is an effective treatment in relapsed FL patients who respond to the previous line and has to be considered as an adequate alternative for some patients.

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References

  1. Swerdlow S, Campo E, Harris NL. et al. Follicular Lymphoma. WHO Classification of tumours of haematopoietic and lymphoid tissues. Revised 4th Edition, 266-273. 2017.

  2. Tan D, Horning SJ, Hoppe RT. Levy R, Rosenberg SA, Sigal BM, Warnke RA, Natkunam Y, Han SS, Yuen A, Plevritis SK, Advani RH. (2013) Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Standford University experience. Blood. ;122(6):981-987. https://doi.org/10.1182/blood-2013-03-491514.

  3. Magnano L, Alonso-Alvarez S, Alcoceba M, Rivas-Delgado A, Muntañola A, Nadeu F, Setoain X, Rodríguez S, Andrade-Campos M, Espinosa-Lara N, Rodríguez G, Sancho JM, Moreno M, Mercadal S, Carro I, Salar A, Garcia-Pallarols F, Arranz R, Cannata J, Terol MJ, Teruel AI, Jiménez-Ubieto A, Rodriguez A, González de Villambrosía S, Bello JL, López L, Novelli S, de Cabo E, Infante ME, Pardal E, Monsalvo S, González M, Martín A, Caballero MD, López-Guillermo A, Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) (2019) Life expectancy of follicular lymphoma patients in complete response at 30 months is similar to that of the Spanish general population. Br J Haematol 185(3):480–491. https://doi.org/10.1111/bjh.15805

    Article  CAS  PubMed  Google Scholar 

  4. Maurer MJ, Bachy E, Ghesquières H, Ansell SM, Nowakowski GS, Thompson CA, Inwards DJ, Allmer C, Chassagne-Clément C, Nicolas-Virelizier E, Sebban C, Lebras L, Sarkozy C, Macon WR, Feldman AL, Syrbu SI, Traverse-Glehan A, Coiffier B, Slager SL, Weiner GJ, Witzig TE, Habermann TM, Salles G, Cerhan JR, Link BK (2016) Early event status informs subsequent outcome in newly diagnosed follicular lymphoma. Am JHematol 91(11):1096–1101. https://doi.org/10.1002/ajh.24492

    Article  Google Scholar 

  5. Rivas-Delgado A, Magnano L, Moreno-Velázquez M, Garcia O, Nadeu F, Mozas P, Dlouhy I, Baumann T, Rovira J, González-Farré B, Martínez A, Balagué O, Delgado J, Villamor N, Giné E, Campo E, Sancho-Cía JM, López-Guillermo A (2019) Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era. Br J Haematol 184(5):753–759. https://doi.org/10.1111/bjh.15708

    Article  CAS  PubMed  Google Scholar 

  6. Erblich T, Montoto S (2018) Treating relapsed follicular lymphoma. Expert Rev Hematol 11(5):403–410. https://doi.org/10.1080/17474086.2018

    Article  CAS  PubMed  Google Scholar 

  7. Martin A, Conde E, Arnán M, Canales MA, Deben G, Sancho JM, Andreu R, Salar A, García-Sanchez P, Vázquez L, Nistal S, Requena MJ, Donato EM, González JA, León A, Ruiz C, Grande C, González-Barca E, Caballero MD, Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO Cooperative Group) (2008) R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica 93(12):1829–1836. https://doi.org/10.3324/haematol.13440

    Article  CAS  PubMed  Google Scholar 

  8. Ueda K, Nannya Y, Asai T, Amamoto G, Hangaishi A, Takahashi T, Imai T, Kurokawa M (2010) Efficacy and safety of modified rituximab-ESHAP therapy for relapsed/refractory B-cell lymphoma. J Chemother 2010 22(1):54–57. https://doi.org/10.1179/joc.2010.22.1.54

    Article  CAS  Google Scholar 

  9. Lignon J, Sibon D, Madelaine I, Brice P, Franchi P, Briere J, Mounier N, Gisselbrecht C, Faure P, Thieblemont C (2010) Rituximab, dexamethasone, cytarabine and oxaliplatin (R-DHAX) is an effective and safe salvage regimen in relapsed/refractory B-cell Non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk 10(4):262–269. https://doi.org/10.3816/CLML.2010.n.055

    Article  CAS  PubMed  Google Scholar 

  10. Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17(4):1244–1253. https://doi.org/10.1200/JCO.1999.17.4.1244

    Article  CAS  PubMed  Google Scholar 

  11. Crump M, Kuruvilla J, Couban S, MacDonald DA, Kukreti V, Kouroukis CT, Rubinger M, Buckstein R, Imrie KR, Federico M, Di Renzo N, Howson-Jan K, Baetz T, Kaizer L, Voralia M, Olney HJ, Turner AR, Sussman J, Hay AE, Djurfeldt MS, Meyer RM, Chen BE, Shepherd LE (2014) Randomized comparison of gemcitabine, dexamethasone, and cisplatin versus dexamethasone, cytarabine, and cisplatin chemotherapy before autologous stem-cell transplantation for relapsed and refractory aggressive lymphomas: NCIC-CTG LY.12. J Clin Oncol 32(31):3490–3496. https://doi.org/10.1200/JCO.2013.53.9593

    Article  CAS  PubMed  Google Scholar 

  12. Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Brière J, Moskowitz CH, Schmitz N (2010) R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by autologous stem cell transplantation: CORAL study. J Clin Oncol 28(27):4184–4190. https://doi.org/10.1200/JCO.2010.28.1618

    Article  PubMed  PubMed Central  Google Scholar 

  13. Thieblemont C, Gisselbrecht C (2009) Second-line treatment paradigms for diffuse large B-cell lymphomas. Curr Oncol Rep 2009 11:386–393. https://doi.org/10.1007/s11912-009-0052-0

    Article  Google Scholar 

  14. Pettengell R, Uddin R, Boumendil A. et al. (2017) Durable benefit of rituximab maintenance post-autograft in patients with relapsed follicular lymphoma: 12-year follow-up of the EBMT Lymphoma Working Party LYM1 trial. 15th International Conference on Malignant Lymphoma (ICML)

  15. Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnsen HE, Doorduijn JK, Sydes MR, Kvalheim G (2003) High-dose therapy improves progression free survival and survival in relapsed follicular non-Hodgkin’s lymphoma: results from the randomized European CUP trial. J Clin Oncol 21(21):3918–3927. https://doi.org/10.1200/JCO.2003.10.023

    Article  CAS  PubMed  Google Scholar 

  16. Casulo C, Friedberg JW, Ahn KW, Zhou X, Farber CM, Flowers CR, Hainsworth JF, Maurer MJ, Cerhan JR, Link BK, Zelenetz AD, Friedberg JW (2018) 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 24(6):1163–1171. https://doi.org/10.1016/j.bbmt.2017.12.771

    Article  PubMed  Google Scholar 

  17. Jiménez-Ubieto A, Grande C, Caballero D, Yañez L, Novelli S, Hernández-García MT, Manzanares M, Arranz R, Ferrerio JJ, Bobillo S, Mercadal S et al (2019) 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 12(4):194–120. https://doi.org/10.1002/hon.2553

    Article  PubMed  Google Scholar 

  18. Montoto S, Corradini P, Dreyling M et al (2013) Indications for hematopoietic stem cell transplantation in patients with follicular lymphoma: a consensus project of the EBMT-Lymphoma Working Party. Haematologica 98(7):1014–1021. https://doi.org/10.3324/haematol.2013.084723

    Article  PubMed  PubMed Central  Google Scholar 

  19. Thieblemont C, Briere J, Mounier N (2011) The germinal center/activated B cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study. J Clin Oncol 29(31):4079–4087. https://doi.org/10.1200/JCO.2011.35.4423

    Article  PubMed  Google Scholar 

  20. Casulo C, Byrtek M, Dawson KL, Zhou X, Farber C, Flowers C, Hainsworth J, Maurer M, Cerhan J, Link B, Zelenetz A, Friedberg J (2015) (2015) Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis fromthe National LymphoCare Study. J Clin Oncol 33:2516–2522. https://doi.org/10.1200/jco.2014.59.7534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gopal AK, Kahl BS, de Vos S, Wagner-Johnston N, Schuster S, Jurczak W, Flinn I, Flowers C, Martin P, Viardot A, Blum K, Goy A, Davies A, Zinzani PL, Dreyling M, Johnson D, Miller L, Holes L, Li D, Dansey R, Godfrey W, Salles G (2014) PI3K delta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med 370:1008–1018. https://doi.org/10.1056/NEJMoa1314583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Guione P, Cavallo F, Visco C, Chen Z, Castellino A, Tisi M, Dogliotti I, Nicolosi M, Boccadoro M, Leonard J, Vitolo U, Martin P (2018) A retrospective study of RDHAP/Ox for early progressing follicular lymphoma. Br J Haematol 183(5):828–831. https://doi.org/10.1111/bjh.15057

    Article  Google Scholar 

  23. Peñalver FJ, Márquez JA, Durán S, Giraldo P, Martín A, Montalbán C, Sancho JM, Ramírez MJ, Terol MJ, Capote FJ, Gutiérrez A, Sánchez B, López A, Salar A, Rodríguez-Caravaca G, Canales M, Caballero D (2019) Response-adapted treatment with rituximab, bendamustine, mitoxantrone, and dexamethasone followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma after first-line immunochemotherapy: Results of the RBMDGELTAMO08 phase II trial. Cancer Med 8(16):6955–6966. https://doi.org/10.1002/cam4.2555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Forstpointner R, Unterhalt M, Dreyling M, Böck HP, Repp R, Wandt H, Pott C, Seymour JF, Metzner B, Hänel A, Lehmann T, Hartmann F, Einsele H, Hiddemann W (2008) Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood 108(13):4003–4008. https://doi.org/10.1182/blood-2006-04-016725

    Article  CAS  Google Scholar 

  25. Witzig TE, Gordon LI, Cabanillas F, Czuczman M, Emmanouillides C, Pohlman R, Bartlett N, Wiseman G, Padre N, Grillo-López A, Multani P, White C (2002) 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. J Clin Oncol 20:2453–2463. https://doi.org/10.1200/JCO.2002.11.076

    Article  CAS  PubMed  Google Scholar 

  26. Sehn LH, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben L, Lennard A, Lugtenburg P, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson B (2016) Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximabrefractory indolent non-Hodgkin lymphoma (GADOLIN): a randomized, controlled, open-label, multicenter, phase 3 trial. Lancet Oncol 17(8):1081–1093. https://doi.org/10.1016/S1470-2045(16)30097-3

    Article  CAS  PubMed  Google Scholar 

  27. Cheson BD, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben L, Lennard A, Lugtenburg P, Fingerle-Rowson G, Mattiello F, Knapp A, Sehn L (2018) 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 36(22):2259–2266. https://doi.org/10.1200/jco.2017.76.3656

    Article  CAS  PubMed  Google Scholar 

  28. Dreyling M, Santoro A, Mollica L, Leppa S, Follows G, Lenz G, Seog Kim W, Nagler A, Panagiotidis P, Demeter J, Özcan M, Kosinova M, Zinzani PL (2017) Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma. J Clin Oncol 35(35):3898–3905. https://doi.org/10.1200/jco.2017.75.4648

    Article  CAS  PubMed  Google Scholar 

  29. Flinn IW, Miller CB, Ardeshna KM, Tetreault S, Assouline S, Mayer S, Merli M, Lunin S, Pettitt A, Nagy Z, Tournilhac O…et Zinzani PL. (2019) DYNAMO: a phase II study of duvelisib (IPI-145) in patients with refractory indolent non-Hodgkin lymphoma. J Clin Oncol. ;37(11):912-922. https://doi.org/10.1200/jco.18.00915.

  30. Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G, Kaplan H, Voralia M, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis J, Vose J (2009) Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin’s lymphoma. J Clin Oncol 27(32):5404–5409. https://doi.org/10.1200/jco.2008.21.1169

    Article  CAS  PubMed  Google Scholar 

  31. Leonard J, Trneny M, Izutsu K, Fowler N, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski G, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn I, Moreira C, Cabeçades J, Liu D, Kalambakas S, Fustier P, Nu C, Gribben J (2019) AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol 37(14):1188–1199. https://doi.org/10.1200/jco.19.00010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Hematology Department, Hospital Universitari Mútua Terrassa, Pl. Dr. Robert 5, 08221, Terrassa, Barcelona, Spain

    A. Muntañola, M. Canet & M. T. Villalobos

  2. Hospital Clínic Barcelona, Barcelona, Spain

    T. Baumann, L. Magnano & A. López-Guillermo

  3. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    A. C. Caballero

  4. Hospital del Mar, Barcelona, Spain

    B. Sánchez-González & A. Salar

  5. Hospital Duran i Reynals-ICO Hospitalet, Barcelona, Spain

    S. Mercadal

  6. Hospital Joan XXIII-ICO Tarragona, Tarragona, Spain

    L. Escoda

  7. Hospital Parc Taulí, Parc Taulí, Spain

    A. Soler

  8. Hospital Arnau de Vilanova, Valencia, Spain

    L. Iserte

  9. Hospital Germans Trias i Pujol-ICO Badalona, Badalona, Spain

    M. Sorigué, O. García & J. M. Sancho

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  1. A. Muntañola
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  2. T. Baumann
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  5. S. Mercadal
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Contributions

AM provided and centralized clinical data, interpreted data, wrote the manuscript and contributed to the conception of the study. OG performed statistical analyses. TB, BSG, ACC, SM, LE, MC, MTV, LI, JAS and MS provided clinical data. AS provided clinical data and interpreted data. ALG supervised the research, interpreted data and wrote the manuscript. JMS supervised the research, designed the study, interpreted data and wrote the manuscript.

Corresponding author

Correspondence to A. Muntañola.

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Conflict of interest

AM has received a speaker honorarium and travel grants from Roche, Abbvie and Janssen and has participated in advisory boards for Roche, Abbvie and Janssen. TB has received lecture fees from Janssen, Abbvie and Gilead/Kite and has participated in advisory boards for Janssen. BSG reports none institutional research funding and is a consultant and/or speaker bureau for Novartis, Amgen, Takeda, Alexion, Gilead and Shire. SM has received lecture fees and travel grants from Roche. AS participated in a speaker’s bureau for Roche and Janssen, received travel grants from Roche, served on the advisory board of Celgene, Roche, Janssen and reports research funding from Roche and Gilead. ALG served on the advisory board of Roche, Celgene, Novartis, Gilead/Kite and received grants from Celgene, Gilead/Kite. JMS reports honoraria from Roche, Janssen, Gilead, Celgene, Novartis, Kern-pharma and Servier and has participated in advisory boards for Roche, Janssen, Gilead, Celgene, Novartis, Kern- Pharma and Celltrion. The remaining authors (ACC, LI, LE, JAS, MC, MTV, LM, OG and MS) have no conflict of interest.

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All procedures performed in the study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participant who was alive at the moment of the study onset.

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Muntañola, A., Baumann, T., Caballero, A.C. et al. Results of R-ESHAP as salvage therapy in refractory/relapsed follicular lymphoma: a real-world experience on behalf of GELCAB group. Ann Hematol 99, 1627–1634 (2020). https://doi.org/10.1007/s00277-020-04101-7

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