Abstract
Bendamustine plus rituximab (BR) showed efficacy and safety in indolent lymphomas and mantle cell lymphoma. However, there were limited experiences of real-world practice of BR in diffuse large B cell lymphoma (DLBCL). In this study, we report the Korean experiences with BR in relapsed or refractory DLBCL who are not eligible for intensive chemotherapy and autologous stem cell transplantation. This is an observational, multicenter, retrospective analysis. Between December 2011 and December 2015, a total of 58 patients with relapsed or refractory DLBCL were treated with BR in 11 tertiary hospitals in Korea. Patients received an intravenous (IV) infusion of rituximab at a dose of 375 mg/m2 on day 1. On days 2 and 3, patients received an IV infusion of bendamustine at doses of 120 or 90 mg/m2. Median age was 69 (range 18–86), 74.1% had stage III or IV disease, and 67.2% showed high-intermediate or high International Prognostic Index scores at diagnosis. In an intention-to-treat analysis, 18 patients (31.0%) showed a complete response and 14 (24.1%) showed a partial response, resulting in an overall response rate of 55.1%. The median duration of the response was 3.7 months (range 1.0–47.2 months). The median progression-free survival was 3.9 months (95% confidence interval [CI], 2.4–5.4 months), and the median overall survival was 6.7 months (95% CI, 4.7–8.7 months). The most common grade 3/4 adverse event was neutropenia (n = 40; 68.9%). Febrile neutropenia was observed in 11 patients (18.9%). Grade 3/4 thrombocytopenia was observed in 34 patients (58.6%). Our study confirmed the high efficacy and acceptable toxicity profile of BR in relapsed or refractory DLBCL patients. However, we need to closely observe the higher tendency of grade 3/4 hematological toxicities in Korean patients.
Similar content being viewed by others
References
Fisher SG, Fisher RI (2004) The epidemiology of non-Hodgkin’s lymphoma. Oncogene 23:6524–6534. https://doi.org/10.1038/sj.onc.1207843
Pfreundschuh M, Trumper L, Osterborg A et al (2006) CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 7:379–391. https://doi.org/10.1016/S1470-2045(06)70664-7
Hong JY, Suh C, Kim WS (2016) Evolution of frontline treatment of diffuse large B-cell lymphoma: a brief review and recent update. F1000Res 5. https://doi.org/10.12688/f1000research.8790.1
Friedberg JW (2011) Relapsed/refractory diffuse large B-cell lymphoma. Hematol Am Soc Hematol Educ Program 2011:498–505. https://doi.org/10.1182/asheducation-2011.1.498
Philip T, Guglielmi C, Hagenbeek A, Somers R, van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F (1995) Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med 333:1540–1545. https://doi.org/10.1056/NEJM199512073332305
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) Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol Off J Am Soc Clin Oncol 28:4184–4190. https://doi.org/10.1200/JCO.2010.28.1618
Cheson BD, Rummel MJ (2009) Bendamustine: rebirth of an old drug. J Clin Oncol Off J Am Soc Clin Oncol 27:1492–1501. https://doi.org/10.1200/JCO.2008.18.7252
Rummel MJ, Chow KU, Hoelzer D, Mitrou PS, Weidmann E (2002) In vitro studies with bendamustine: enhanced activity in combination with rituximab. Semin Oncol 29:12–14
Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 381:1203–1210. https://doi.org/10.1016/S0140-6736(12)61763-2
Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, MacDonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM (2014) Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood 123:2944–2952. https://doi.org/10.1182/blood-2013-11-531327
Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, Terauchi T, Tateishi U, Tatsumi M, Kim WS, Tobinai K, Suh C, Ogura M (2013) Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 31:2103–2109. https://doi.org/10.1200/JCO.2012.46.5203
Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E (2014) Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol 93:403–409. https://doi.org/10.1007/s00277-013-1879-x
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 Off J Am Soc Clin Oncol 17:1244. https://doi.org/10.1200/jco.1999.17.4.1244
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 Off J Am Soc Clin Oncol 25:579–586. https://doi.org/10.1200/JCO.2006.09.2403
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 Off J Am Soc Clin Oncol 32:3490–3496. https://doi.org/10.1200/JCO.2013.53.9593
Merchionne F, Quintana G, Gaudio F, Minoia C, Specchia G, Guarini A, Quarta G, Pavone V, Melpignano A (2014) Bendamustine plus rituximab for relapsed or refractory diffuse large B cell lymphoma: a retrospective analysis. Leuk Res 38:1446–1450. https://doi.org/10.1016/j.leukres.2014.10.001
Arcari A, Chiappella A, Spina M, Zanlari L, Bernuzzi P, Valenti V, Tani M, Marasca R, Cabras MG, Zambello R, Santagostino A, Ilariucci F, Carli G, Musto P, Savini P, Marino D, Ghio F, Gentile M, Cox MC, Vallisa D (2016) Safety and efficacy of rituximab plus bendamustine in relapsed or refractory diffuse large B-cell lymphoma patients: an Italian retrospective multicenter study. Leuk Lymphoma 57:1823–1830. https://doi.org/10.3109/10428194.2015.1106536
Cheson BD, Brugger W, Damaj G, Dreyling M, Kahl B, Kimby E, Ogura M, Weidmann E, Wendtner CM, Zinzani PL (2016) Optimal use of bendamustine in hematologic disorders: treatment recommendations from an international consensus panel - an update. Leuk Lymphoma 57:766–782. https://doi.org/10.3109/10428194.2015.1099647
Acknowledgements
This study was supported by a grant (2017-738) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Hong, J.Y., Yoon, D.H., Suh, C. et al. Bendamustine plus rituximab for relapsed or refractory diffuse large B cell lymphoma: a multicenter retrospective analysis. Ann Hematol 97, 1437–1443 (2018). https://doi.org/10.1007/s00277-018-3317-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-018-3317-6