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Erschienen in: Annals of Hematology 2/2018

14.11.2017 | Original Article

Delayed recovery of serum immunoglobulin G is a poor prognostic marker in patients with follicular lymphoma treated with rituximab maintenance

verfasst von: Yoshiharu Kusano, Masahiro Yokoyama, Norihito Inoue, Hirofumi Yamauchi, Anna Takahashi, Naoko Tsuyama, Yuko Mishima, Noriko Nishimura, Kengo Takeuchi, Yasuhito Terui, Kiyohiko Hatake

Erschienen in: Annals of Hematology | Ausgabe 2/2018

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Abstract

Clinical trials involving various treatment schedules for rituximab maintenance have been conducted for patients with follicular lymphoma (FL) and have not confirmed their impact on serum immunoglobulin (sIg) levels until the completion of maintenance. However, the long-term use of rituximab is a concern because of circulating plasma cell-depletion risk, suggesting that the mechanism of change in sIg levels after RM has not been determined. Additionally, the relationship between host humoral immunity and the prognosis of patients with B cell malignancies has not been determined. We retrospectively investigated data from 213 patients with FL from a single institute who achieved at least a partial response with rituximab, cyclophosphamide, vincristine, and prednisolone with or without doxorubicin. Of these, 166 patients underwent RM with a median period of 1.6 years. A significantly delayed recovery of sIgG levels was observed in the maintenance group until 3 years after RM in comparison to the observation group. A multivariate analysis showed that a sIgG level of < 718 mg/dl 1 year after RM was an independent predictor for poor progression-free survival (PFS) (hazard ratio, 2.3; P = 0.04). Therefore, the sIgG levels scarcely recovered and were significantly delayed after RM, leading to shorter PFS in patients with FL.
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Literatur
1.
Zurück zum Zitat Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83(2):435–445PubMed Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83(2):435–445PubMed
2.
Zurück zum Zitat Maloney DG, Smith B, Rose A (2002) Rituximab: mechanism of action and resistance. Semin Oncol 2–9(suppl 2):29 Maloney DG, Smith B, Rose A (2002) Rituximab: mechanism of action and resistance. Semin Oncol 2–9(suppl 2):29
3.
Zurück zum Zitat Shan D, Ledbetter JA, Press OW (1998) Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies. Blood 91(5):1644–1652PubMed Shan D, Ledbetter JA, Press OW (1998) Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies. Blood 91(5):1644–1652PubMed
6.
Zurück zum Zitat Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T (2004) Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly 4 schedule. Blood 103(12):4416–4423. https://doi.org/10.1182/blood-2003-10-3411 CrossRefPubMed Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, Fey MF, Betticher DC, Martinelli G, Peccatori F, Hess U, Zucca E, Stupp R, Kovacsovics T, Helg C, Lohri A, Bargetzi M, Vorobiof D, Cerny T (2004) Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly 4 schedule. Blood 103(12):4416–4423. https://​doi.​org/​10.​1182/​blood-2003-10-3411 CrossRefPubMed
8.
Zurück zum Zitat Taverna CJ, Bassi S, Hitz F et al (2010) Rituximab maintenance treatment for a maximum of 5 years in follicular lymphoma: Safety analysis of the randomized phase III trial SAKK 35/03. Blood 116:1802 1802 (abstract 1802) Taverna CJ, Bassi S, Hitz F et al (2010) Rituximab maintenance treatment for a maximum of 5 years in follicular lymphoma: Safety analysis of the randomized phase III trial SAKK 35/03. Blood 116:1802 1802 (abstract 1802)
9.
Zurück zum Zitat Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H (2010) 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. Lancet 377(9759):42–51. https://doi.org/10.1016/S0140-6736(10)62175-7 CrossRefPubMed Salles G, Seymour JF, Offner F, López-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Fermé C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H (2010) 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. Lancet 377(9759):42–51. https://​doi.​org/​10.​1016/​S0140-6736(10)62175-7 CrossRefPubMed
10.
Zurück zum Zitat van der Kolk LE, Baars JW, Prins MH, van Oers MH (2002) Rituximab treatment results in impaired secondary humoral immune responsiveness. Blood 100(6):2257–2259PubMed van der Kolk LE, Baars JW, Prins MH, van Oers MH (2002) Rituximab treatment results in impaired secondary humoral immune responsiveness. Blood 100(6):2257–2259PubMed
13.
Zurück zum Zitat Cavanillas F, Liboy I, Pavia O et al (2006) High incidence of non-neutropenic infections induced by rituximab plus fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized and easily treatable complication. Ann Oncol 17(9):1424–1427. https://doi.org/10.1093/annonc/mdl141 CrossRef Cavanillas F, Liboy I, Pavia O et al (2006) High incidence of non-neutropenic infections induced by rituximab plus fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized and easily treatable complication. Ann Oncol 17(9):1424–1427. https://​doi.​org/​10.​1093/​annonc/​mdl141 CrossRef
16.
Zurück zum Zitat Nishio M, Fujimoto K, Yamamoto S, Endo T, Sakai T, Obara M, Kumano K, Minauchi K, Yamaguchi K, Takeda Y, Sato N, Koizumi K, Mukai M, Koike T (2006) Hypogammaglobulinemia with delayed recovery in memory B cells and an impaired isotype expression after expression after rituximab administration as an adjuvant to autologous stem cell transplantation for non-Hodgkin lymphoma. Eur J Haematol 77(3):226–232. https://doi.org/10.1111/j.1600-0609.2006.00693.x CrossRefPubMed Nishio M, Fujimoto K, Yamamoto S, Endo T, Sakai T, Obara M, Kumano K, Minauchi K, Yamaguchi K, Takeda Y, Sato N, Koizumi K, Mukai M, Koike T (2006) Hypogammaglobulinemia with delayed recovery in memory B cells and an impaired isotype expression after expression after rituximab administration as an adjuvant to autologous stem cell transplantation for non-Hodgkin lymphoma. Eur J Haematol 77(3):226–232. https://​doi.​org/​10.​1111/​j.​1600-0609.​2006.​00693.​x CrossRefPubMed
17.
Zurück zum Zitat Irie E, Shirota Y, Suzuki C, Tajima Y, Ishizawa K, Kameoka J, Harigae H, Ishii T (2010) Severe hypogammaglobulinemia persisting for 6 years after treatment with rituximab combined chemotherapy due to arrest of B lymphocyte differentiation together with alteration of T lymphocyte homeostasis. Int J Hematol 91(3):501–508. https://doi.org/10.1007/s12185-010-0528-6 CrossRefPubMed Irie E, Shirota Y, Suzuki C, Tajima Y, Ishizawa K, Kameoka J, Harigae H, Ishii T (2010) Severe hypogammaglobulinemia persisting for 6 years after treatment with rituximab combined chemotherapy due to arrest of B lymphocyte differentiation together with alteration of T lymphocyte homeostasis. Int J Hematol 91(3):501–508. https://​doi.​org/​10.​1007/​s12185-010-0528-6 CrossRefPubMed
19.
Zurück zum Zitat Levy R, Mahévas M, Galicier L, Boutboul D, Moroch J, Loustau V, Guillaud C, Languille L, Fain O, Bierling P, Khellaf M, Michel M, Oksenhendler E, Godeau B (2014) Profound symptomatic hypogammaglobulinemia: a rare late complication after rituximab treatment for immune thrombocytopenia. Report of 3 cases and systematic review of the literature. Autoimmun Rev 13(10):1055–1063. https://doi.org/10.1016/j.autrev.2014.08.036 CrossRefPubMed Levy R, Mahévas M, Galicier L, Boutboul D, Moroch J, Loustau V, Guillaud C, Languille L, Fain O, Bierling P, Khellaf M, Michel M, Oksenhendler E, Godeau B (2014) Profound symptomatic hypogammaglobulinemia: a rare late complication after rituximab treatment for immune thrombocytopenia. Report of 3 cases and systematic review of the literature. Autoimmun Rev 13(10):1055–1063. https://​doi.​org/​10.​1016/​j.​autrev.​2014.​08.​036 CrossRefPubMed
26.
Zurück zum Zitat Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon. IARC Press, Lyon Swerdlow SH, Campo E, Harris NL et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon. IARC Press, Lyon
27.
Zurück zum Zitat Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V, International Harmonization Project on Lymphoma (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–586. https://doi.org/10.1200/JCO.2006.09.2403 CrossRefPubMed Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V, International Harmonization Project on Lymphoma (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–586. https://​doi.​org/​10.​1200/​JCO.​2006.​09.​2403 CrossRefPubMed
29.
Zurück zum Zitat Hochster HS, Weller E, Gascoyne R et al (2007) Cyclophosphamide/fludarabine (CF) in advanced indolent lymphoma: results from the E1496 Trial. J Clin Oncol 25(18):8004 8004 (abstract 8004) Hochster HS, Weller E, Gascoyne R et al (2007) Cyclophosphamide/fludarabine (CF) in advanced indolent lymphoma: results from the E1496 Trial. J Clin Oncol 25(18):8004 8004 (abstract 8004)
31.
Zurück zum Zitat Lu H, Pundole X (2014) Factors predicting long-term hypogammaglobulinemia in lymphoma survivors. J Allergy Clin Imunol 44(2):AB10CrossRef Lu H, Pundole X (2014) Factors predicting long-term hypogammaglobulinemia in lymphoma survivors. J Allergy Clin Imunol 44(2):AB10CrossRef
35.
Zurück zum Zitat Bendandi M, Gocke CD, Kobrin CB, Benko FA, Sternas LA, Pennington R, Watson TM, Reynolds CW, Gause BL, Duffey PL, Jaffe ES, Creekmore SP, Longo DL, Kwak LW (1999) Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony stimulating factor against lymphoma. Nat Med 5(10):1171–1177. https://doi.org/10.1038/13928 CrossRefPubMed Bendandi M, Gocke CD, Kobrin CB, Benko FA, Sternas LA, Pennington R, Watson TM, Reynolds CW, Gause BL, Duffey PL, Jaffe ES, Creekmore SP, Longo DL, Kwak LW (1999) Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony stimulating factor against lymphoma. Nat Med 5(10):1171–1177. https://​doi.​org/​10.​1038/​13928 CrossRefPubMed
37.
Zurück zum Zitat Hsu FJ, Caspar CB, Czerwinski D, Kwak LW, Liles TM, Syrengelas A, Taidi-Laskowski B, Levy R (1997) Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma—long-term results of a clinical trial. Blood 89(9):3129–3135PubMed Hsu FJ, Caspar CB, Czerwinski D, Kwak LW, Liles TM, Syrengelas A, Taidi-Laskowski B, Levy R (1997) Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma—long-term results of a clinical trial. Blood 89(9):3129–3135PubMed
38.
39.
Zurück zum Zitat Levy R, Robertson MJ, Ganjoo K, et al. Results of a phase 3 trial evaluating safety and efficacy of specific immunotherapy, recombinant idiotype (Id) conjugated to KLH (Id-KLH) with GM-CSF, compared to nonspecific immunotherapy, KLH with GM-CSF, in patients with follicular non-Hodgkin’s lymphoma (fNHL). AACR meeting; 2008 Abstract LB-204 Levy R, Robertson MJ, Ganjoo K, et al. Results of a phase 3 trial evaluating safety and efficacy of specific immunotherapy, recombinant idiotype (Id) conjugated to KLH (Id-KLH) with GM-CSF, compared to nonspecific immunotherapy, KLH with GM-CSF, in patients with follicular non-Hodgkin’s lymphoma (fNHL). AACR meeting; 2008 Abstract LB-204
40.
Zurück zum Zitat Ai WZ, Tibshirani R, Taidi B et al (2009) Anti-idiotype antibody response after vaccination correlates with better overall survival in follicular lymphoma. Blood 113:5743–5746 Ai WZ, Tibshirani R, Taidi B et al (2009) Anti-idiotype antibody response after vaccination correlates with better overall survival in follicular lymphoma. Blood 113:5743–5746
42.
Zurück zum Zitat Redfern CH, Guthrie TH, Bessudo A, Densmore JJ, Holman PR, Janakiraman N, Leonard JP, Levy RL, Just RG, Smith MR, Rosenfelt FP, Wiernik PH, Carter WD, Gold DP, Melink TJ, Gutheil JC, Bender JF (2006) Phase II trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin’s lymphoma resulting in durable clinical responses. J Clin Oncol 24(19):3107–3112. https://doi.org/10.1200/JCO.2005.04.4289 CrossRefPubMed Redfern CH, Guthrie TH, Bessudo A, Densmore JJ, Holman PR, Janakiraman N, Leonard JP, Levy RL, Just RG, Smith MR, Rosenfelt FP, Wiernik PH, Carter WD, Gold DP, Melink TJ, Gutheil JC, Bender JF (2006) Phase II trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin’s lymphoma resulting in durable clinical responses. J Clin Oncol 24(19):3107–3112. https://​doi.​org/​10.​1200/​JCO.​2005.​04.​4289 CrossRefPubMed
43.
Zurück zum Zitat Flinn I, Van der Jagt R, Chang JE et al (2017) First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. J Clin Oncol 35(15 suppl):7500–7500 Flinn I, Van der Jagt R, Chang JE et al (2017) First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. J Clin Oncol 35(15 suppl):7500–7500
44.
Zurück zum Zitat Rummel MJ, Maschmeyer G, Ganser A et al (2017) Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. J Clin Oncol 35(15 suppl):7501–7501 Rummel MJ, Maschmeyer G, Ganser A et al (2017) Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. J Clin Oncol 35(15 suppl):7501–7501
45.
Zurück zum Zitat Solal-Céligny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, Au WY, Bellei M, Brice P, Caballero D, Coiffier B, Conde-Garcia E, Doyen C, Federico M, Fisher RI, Garcia-Conde JF, Guglielmi C, Hagenbeek A, Haïoun C, LeBlanc M, Lister AT, Lopez-Guillermo A, McLaughlin P, Milpied N, Morel P, Mounier N, Proctor SJ, Rohatiner A, Smith P, Soubeyran P, Tilly H, Vitolo U, Zinzani PL, Zucca E, Montserrat E (2004) Follicular lymphoma international prognostic index. Blood 104(5):1258–1265. https://doi.org/10.1182/blood-2003-12-4434 CrossRefPubMed Solal-Céligny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, Au WY, Bellei M, Brice P, Caballero D, Coiffier B, Conde-Garcia E, Doyen C, Federico M, Fisher RI, Garcia-Conde JF, Guglielmi C, Hagenbeek A, Haïoun C, LeBlanc M, Lister AT, Lopez-Guillermo A, McLaughlin P, Milpied N, Morel P, Mounier N, Proctor SJ, Rohatiner A, Smith P, Soubeyran P, Tilly H, Vitolo U, Zinzani PL, Zucca E, Montserrat E (2004) Follicular lymphoma international prognostic index. Blood 104(5):1258–1265. https://​doi.​org/​10.​1182/​blood-2003-12-4434 CrossRefPubMed
46.
Zurück zum Zitat Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, Pro B, Pileri S, Pulsoni A, Soubeyran P, Cortelazzo S, Martinelli G, Martelli M, Rigacci L, Arcaini L, di Raimondo F, Merli F, Sabattini E, McLaughlin P, Solal-Céligny P (2009) Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol 27(27):4555–4562. https://doi.org/10.1200/JCO.2008.21.3991 CrossRefPubMed Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, Pro B, Pileri S, Pulsoni A, Soubeyran P, Cortelazzo S, Martinelli G, Martelli M, Rigacci L, Arcaini L, di Raimondo F, Merli F, Sabattini E, McLaughlin P, Solal-Céligny P (2009) Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol 27(27):4555–4562. https://​doi.​org/​10.​1200/​JCO.​2008.​21.​3991 CrossRefPubMed
Metadaten
Titel
Delayed recovery of serum immunoglobulin G is a poor prognostic marker in patients with follicular lymphoma treated with rituximab maintenance
verfasst von
Yoshiharu Kusano
Masahiro Yokoyama
Norihito Inoue
Hirofumi Yamauchi
Anna Takahashi
Naoko Tsuyama
Yuko Mishima
Noriko Nishimura
Kengo Takeuchi
Yasuhito Terui
Kiyohiko Hatake
Publikationsdatum
14.11.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 2/2018
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-017-3175-7

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