Optimal use of bendamustine in hematologic disorders: Treatment recommendations from an international consensus panel – an update

References

• Ozegowski WKD. IMET, 3393 (-[1-methyl-5-bis-(b-chloroethyl)-amino-benzimidazolyl-(2)]-butyric acid hydrochloride, a new cytostatic agent from among the series of benzimidazole mustard compounds. Zbl Pharm Pharmakother Lab 1971; 110: 1013–1019.
   Google Scholar
• Knauf WU, Lissichkov T, Aldaoud A, et al. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol 2009; 27: 4378–4384.
   PubMed Web of Science ®Google Scholar
• Friedberg JW, Cohen P, Chen L, et al. Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study. J Clin Oncol 2008; 26: 204–210.
   PubMed Web of Science ®Google Scholar
• Kahl BS, Bartlett NL, Leonard JP, et al. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer 2010; 116: 106–114.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Wendtner CM, Pieper A, et al. Optimal use of bendamustine in chronic lymphocytic leukemia, non-Hodgkin lymphomas, and multiple myeloma: treatment recommendations from an international consensus panel. Clin Lymphoma Myeloma Leuk 2010; 10: 21–27.
   PubMed Web of Science ®Google Scholar
• Leoni L, Bailey B, Reifert J, et al. Bendamustine (Treanda) displays a distinct pattern of cytotoxicity and unique mechanistic features compared with other alkylating agents. Clin Cancer Res 2008; 14: 309–317.
   PubMed Web of Science ®Google Scholar
• Gandhi V. Metabolism and mechanisms of action of bendamustine rationales for combination therapies. Semin Oncol 2002; 29(Suppl. 13): 4–11.
   PubMed Web of Science ®Google Scholar
• Kath R, Blumenstengel K, Fricke HJ, et al. Bendamustine monotherapy in advanced and refractory chronic lymphocytic leukemia. J Cancer Res Clin Oncol 2001; 127: 48–54.
   PubMed Web of Science ®Google Scholar
• Heider A, Niederle N. Efficacy and toxicity of bendamustine in patients with relapsed low-grade non-Hodgkin’s lymphomas. Anticancer Drugs 2001; 12: 725–729.
   PubMed Web of Science ®Google Scholar
• Teichert J, Baumann F, Chao Q, et al. Characterization of two phase I metabolites of bendamustine in human liver microsomes and in cancer patients treated with bendamustine hydrochloride. Cancer Chemother Pharmacol 2007; 59: 759–70.
   PubMed Web of Science ®Google Scholar
• Treanda® prescribing information. Available from: http://www.treanda.com/pdf/TREANDA_final_PI.pdf
   Google Scholar
• Preiss R, Teichert J, Pönisch W, et al. Pharmacokinetics and toxicity profile of bendamustine in myeloma patients with end-stage renal disease. Hematology J 2003; 4(Suppl. 1):Abstract 394
   Google Scholar
• McCloskey JK, Broome CM, Cheson BD. Safe and effective treatment of aggressive non-hodgkin lymphoma with rituximab and bendamustine in patients with severe liver impairment. Clin Adv Hematol Oncol 2013; 11: 184–188.
   PubMedGoogle Scholar
• Eichhorst B, Fink AM, Busch R, et al. Frontline chemoimmunotherapy with fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) shows superior efficacy in comparison to bendamustine (B) and rituximab (BR) in previously untreated and physically fit patients (pts) with advanced chronic lymphocytic leukemia (CLL): final analysis of an international, randomized study of the German CLL Study Group (GCLLSG) (CLL10 Study). Blood 2014; 124: 19.
   Google Scholar
• Bergmann MA, Goebeler ME, Herold M, et al. Efficacy of bendamustine in patients with relapsed or refractory chronic lymphocytic leukemia: results of a phase I/II study of the German CLL Study Group. Haematologica 2005; 90: 1357–1364.
   PubMed Web of Science ®Google Scholar
• Lissitchkov T, Arnaudov G, Peytchev D, et al. Phase-I/II study to evaluate dose limiting toxicity, maximum tolerated dose, and tolerability of bendamustine HCl in pre-treated patients with B-chronic lymphocytic leukaemia (Binet stages B and C) requiring therapy. J Cancer Res Clin Oncol 2006; 132: 99–104.
   PubMed Web of Science ®Google Scholar
• Fischer K, Cramer P, Busch R, et al. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 2011; 29: 3559–3566.
   PubMed Web of Science ®Google Scholar
• Offner F, Panagiotidis P, Afanasyev B, et al. Ofatumumab and bendamustine combination therapy in patients with untreated and relapsed chronic lymphocytic leukemia: initial results of the phase II study OMB115991. Int Workshop CLL 2013; 4: 29.
   Google Scholar
• Cortelezzi A, Sciume M, Liberati AM, et al. Bendamustine in combination with ofatumumab in relapsed or refractory chronic lymphocytic leukemia: a GIMEMA Multicenter Phase II Trial. Leukemia 2014; 28: 642–648.
   PubMed Web of Science ®Google Scholar
• Brown JR, O'Brien S, Kingsley D, et al. Safety and efficacy of obinutuzumab (GA101) with fludarabine/cyclophosphamide (G-FC) or bendamustine (G-B) in the initial therapy of patients with chronic lymphocytic leukemia (CLL): results from the phase 1b Galton Trial (GAO4779g) [abstract]. Blood (Suppl) 2013; 122: 523.
   PubMed Web of Science ®Google Scholar
• Ujjani C, Ramzi P, Gehan E, et al. Ofatumumab and bendamustine in previously treated chronic lymphocytic leukemia and small lymphocytic lymphoma. Leuk Lymphoma 2015; 56: 915–920.
   PubMed Web of Science ®Google Scholar
• Brown JR, Barrientos JC, Barr PM, et al. Ibrutinib In combination with bendamustine and rituximab Is active and tolerable in patients with relapsed/refractory CLL/SLL: final results of a phase 1b study. Blood 2013; 122: 525.
   Google Scholar
• Rummel MJ, Niederle N, Maschmeyer G, et al. 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 2013; 381: 1203–1210.
   PubMed Web of Science ®Google Scholar
• Fischer K, Cramer P, Busch R, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 2012; 30: 3209–3216.
   PubMed Web of Science ®Google Scholar
• Flinn IW, van der Jagt R, Kahl BS, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood 2014; 123: 2944–2952.
   PubMed Web of Science ®Google Scholar
• Salar A, Domingo-Domenech E, Panizo E, et al. Final results of a multicenter phase II trial with bendamustine and rituximab as first line treatment for patients with MALT lymphoma (MALT-2008-01). Blood 2012; 120: 3691.
   Google Scholar
• Weidmann E, Neumann A, Fauth F, et al. Phase II study of bendamustine in combination with rituximab as first-line treatment in patients 80 years or older with aggressive B-cell lymphomas. Ann Oncol 2011; 22: 1839–1844.
   PubMed Web of Science ®Google Scholar
• Weidmann E, Kim SZ, Rost A, et al. Bendamustine is effective in relapsed or refractory aggressive non-Hodgkin's lymphoma. Ann Oncol 2002; 13: 1285–1289.
   PubMed Web of Science ®Google Scholar
• Ohmachi K, Niitsu N, Uchida T, et al. Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 2013; 31: 2103–2109.
   PubMed Web of Science ®Google Scholar
• Vacirca JL, Acs PI, Tabbara IA, et al. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol 2014; 93: 403–409.
   PubMed Web of Science ®Google Scholar
• Damaj G, Gressin R, Bouabdallah K, et al. Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. J Clin Oncol 2013; 31: 104–110.
   PubMed Web of Science ®Google Scholar
• Zaja F, Baldini L, Ferreri AJ, et al. Bendamustine salvage therapy for T cell neoplasms. Ann Hematol 2013; 92: 1249–1254.
   PubMed Web of Science ®Google Scholar
• Weide R, Feiten S, Friesenhahn V, et al. Retreatment with bendamustine-containing regimens in patients with relapsed/refractory chronic lymphocytic leukemia and indolent B-cell lymphomas achieves high response rates and some long lasting remissions. Leuk Lymphoma 2013; 54: 1640–1646.
   PubMed Web of Science ®Google Scholar
• Rummel MJ, Maschmeyer G, Ganser A, et al. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent and mantle cell lymphomas (MCL) – 7 year updated results from the StiL NHL1 study [abstract]. Blood (Suppl) 2014; 124: 4407.
   Google Scholar
• Kuruvilla J, Assouline S, Hodgson D, et al. A Canadian evidence-based guideline for the first-line treatment of follicular lymphoma: joint consensus of the Lymphoma Canada Scientific Advisory Board. Clin Lymphoma Myeloma Leuk 2015; 15: 59–74.
   PubMed Web of Science ®Google Scholar
• Flinn IW, van RC, Kahl BS, et al. An open-label, randomized study of bendamustine and rituximab (BR) compared with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line treatment of patients with advanced indolent non-hodgkin's lymphoma (NHL) or mantle cell lymphoma (MCL): The Bright Study. Blood 2012; 120: 902.
   Google Scholar
• Rummel MJ, Al-Batran SE, Kim SZ, 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. J Clin Oncol 2005; 23: 3383–3389.
   PubMed Web of Science ®Google Scholar
• Brugger W, Ghielmini M. Bendamustine in indolent non-Hodgkin's lymphoma: a practice guide for patient management. Oncologist 2013; 18: 954–964.
   PubMed Web of Science ®Google Scholar
• Rummel MJ, Kaiser T, Balser C, et al. Bendamustine plus rituximab versus fludarabine plus rituximab in patients with relapsed follicular, indolent and mantle cell lymphomas - final results of the randomized phase III study NHL 2-2003 on behalf of the STIL (Study Group Indolent Lymphomas, Germany). Blood 2010; 116: 856.
   Google Scholar
• Rummel MJ, Balsar C, Kaiser U, et al. Bendamustine plus rituximab versus fludarabine plus rituximab in patients with relapsed follicular, indolent, or mantle cell lymphomas – 8-year follow-up results of the randomized phase III study NHL 2-2003 on behalf of the StiL (Study Group Indolent Lymphomas, Germany). Blood 2014; 124: 145.
   Google Scholar
• Kiesewetter B, Mayerhoefer ME, Lukas J, et al. Rituximab plus bendamustine is active in pretreated patients with extragastric marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma). Ann Hematol 2014; 93: 249–253.
   PubMed Web of Science ®Google Scholar
• Ogura M, Ando K, Taniwaki M, et al. Feasibility and pharmacokinetic study of bendamustine hydrochloride in combination with rituximab in relapsed or refractory aggressive B cell non-Hodgkin's lymphoma. Cancer Sci 2011; 102: 1687–1692.
   PubMed Web of Science ®Google Scholar
• Robinson KS, Williams ME, van der Jagt RH, et al. Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. J Clin Oncol 2008; 26: 4473–4479.
   PubMed Web of Science ®Google Scholar
• Weide R, Hess G, Koppler H, et al. High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Leuk Lymphoma 2007; 48: 1299–1306.
   PubMed Web of Science ®Google Scholar
• Visco C, Finotto S, Zambello R, et al. Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol 2013; 31: 1442–1449.
   PubMed Web of Science ®Google Scholar
• Friedberg JW, Vose JM, Kelly JL, et al. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood 2011; 117: 2807–2812.
   PubMed Web of Science ®Google Scholar
• Jerkeman M, Kolstad A, Laurell A, et al. Lenalidomide, bendamustine, and rituximab as first-line therapy for patients > 65 years with mantle cell lymphoma: results from the phase I portion of the Nordic Lymphoma Group MCL4 (LENA-BERIT) trial. Blood 2011; 118: 2700.
   Google Scholar
• Zaja F, Ferrero S, Stelitano C, et al. Rituximab, lenalidomide, bendamustine second line therapy in mantel cell lymphoma: a phase II study of the fondazione Italiana linfomi (FIL). Hematological Oncology 2015; 33(Suppl. 1):abstract #14.
   Google Scholar
• Hess G, Keller U, Scholz CW, et al. Safety and efficacy of temsirolimus in combination with bendamustine and rituximab in relapsed mantle cell and follicular lymphoma. Leukemia 2015; 29: 1695–1701.
   PubMed Web of Science ®Google Scholar
• Goy A, Sinha R, Williams ME, et al. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. J Clin Oncol 2013; 31: 3688–3695.
   PubMed Web of Science ®Google Scholar
• Hess G, Herbrecht R, Romaguera J, et al. Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 2009; 27: 3822–3829.
   PubMed Web of Science ®Google Scholar
• Wang M, Fayad L, Wagner-Bartak N, et al. Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Lancet Oncol 2012; 13: 716–723.
   PubMed Web of Science ®Google Scholar
• Zinzani PL, Vose JM, Czuczman MS, et al. Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study. Ann Oncol 2013; 24: 2892–2897.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Crawford J. A phase I study of bendamustine, lenalidomide and rituximab in relapsed and refractory lymphomas. Br J Haematol 2015; 169: 528–533.
   PubMed Web of Science ®Google Scholar
• Savage KJ. Therapies for peripheral T-cell lymphomas. Hematology Am Soc Hematol Educ Program 2011; 2011: 515–524.
   PubMed Web of Science ®Google Scholar
• Rosenstein LJ, Link BK. Optimizing chemotherapeutic strategies for peripheral T-cell lymphomas. Clin Lymphoma Myeloma 2008; 8(Suppl. 5): S180–S186.
   PubMedGoogle Scholar
• Schmitz N, Trümper L, Ziepert M, et al. Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group. Blood 2010; 116: 3418–3425.
   PubMed Web of Science ®Google Scholar
• Herbaux C, Genet P, Bouabdallah K, et al. Bendamustine is effective in T-Cell prolymphocytic leukaemia. Br J Haematol 2015; 168: 916–919.
   PubMed Web of Science ®Google Scholar
• Anastasia A, Carlo-Stella C, Corradini P, et al. Bendamustine for Hodgkin lymphoma patients failing autologous or autologous and allogeneic stem cell transplantation: a retrospective study of the Fondazione Italiana Linfomi. Br J Haematol 2014; 166: 140–142.
   PubMed Web of Science ®Google Scholar
• Corazzelli G, Angrilli F, D'Arco A, et al. Efficacy and safety of bendamustine for the treatment of patients with recurring Hodgkin lymphoma. Br J Haematol 2013; 160: 207–215.
   PubMed Web of Science ®Google Scholar
• Ghesquieres H, Stamatoullas A, Casasnovas O, et al. Clinical experience of bendamustine in relapsed or refractory Hodgkin lymphoma: a retrospective analysis of the French compassionate use program in 28 patients. Leuk Lymphoma 2013; 54: 2399–2404.
   PubMed Web of Science ®Google Scholar
• Moskowitz AJ, Hamlin PA Jr, Perales MA, et al. Phase II study of bendamustine in relapsed and refractory Hodgkin lymphoma. J Clin Oncol 2013; 31: 456–460.
   PubMed Web of Science ®Google Scholar
• Younes A, Gopal AK, Smith SE, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol 2012; 30: 2183–2189.
   PubMed Web of Science ®Google Scholar
• Zinzani PL, Derenzini E, Pellegrini C, et al. Bendamustine efficacy in Hodgkin lymphoma patients relapsed/refractory to brentuximab vedotin. Br J Haematol 2013; 163: 681–683.
   PubMed Web of Science ®Google Scholar
• Zinzani PL, Vitolo U, Viviani S, et al. Safety and efficacy of single-agent bendamustine after failure of brentuximab vedotin in patients with relapsed or refractory Hodgkin's lymphoma: experience with 27 patients. Clin Lymphoma Myeloma Leuk 2015; 1: 404–448.
   Web of Science ®Google Scholar
• LaCasce A, Sawas A, Bociek R, et al. A phase 1/2 single-srm, open-label study to evaluate the safety and efficacy of brentuximab vedotin in combination with bendamustine for patients with Hodgkin Lymphoma in the first salvage setting: interim results. Biol Blood Marrow Transplant 2014; 20: S161.
   Web of Science ®Google Scholar
• Pratt G, Bowcock S, Lai M, et al. United Kingdom Myeloma Forum (UKMF) position statement on the use of bendamustine in myeloma. Int J Lab Hematol 2014; 36: 20–28.
   PubMed Web of Science ®Google Scholar
• Pönisch W, Mitrou PS, Merkle K, et al. Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone – a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). J Cancer Res Clin Oncol 2006; 132: 205–212.
   PubMed Web of Science ®Google Scholar
• Pönisch W, Holzvogt B, Plotze M, et al. Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with newly diagnosed/untreated multiple myeloma. J Cancer Res Clin Oncol 2014; 140: 1947–1956.
   PubMed Web of Science ®Google Scholar
• Berenson JR, Yellin O, Bessudo A, et al. Phase I/II trial assessing bendamustine plus bortezomib combination therapy for the treatment of patients with relapsed or refractory multiple myeloma. Br J Haematol 2013; 160: 321–330.
   PubMed Web of Science ®Google Scholar
• Damaj G, Malard F, Hulin C, et al. Efficacy of bendamustine in relapsed/refractory myeloma patients: results from the French compassionate use program. Leuk Lymphoma 2012; 53: 632–634.
   PubMed Web of Science ®Google Scholar
• Grey-Davies E, Bosworth JL, Boyd KD, et al. Bendamustine, Thalidomide and Dexamethasone is an effective salvage regimen for advanced stage multiple myeloma. Br J Haematol 2012; 156: 552–555.
   PubMed Web of Science ®Google Scholar
• Lau IJ, Smith D, Aitchison R, et al. Bendamustine in combination with thalidomide and dexamethasone is a viable salvage option in myeloma relapsed and/or refractory to bortezomib and lenalidomide. Ann Hematol 2015; 94: 643–649.
   PubMed Web of Science ®Google Scholar
• Lentzsch S, O'Sullivan A, Kennedy RC, et al. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood 2012; 119: 4608–4613.
   PubMed Web of Science ®Google Scholar
• Ludwig H, Kasparu H, Leitgeb C, et al. Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood 2014; 123: 985–991.
   PubMed Web of Science ®Google Scholar
• Michael M, Bruns I, Bolke E, et al. Bendamustine in patients with relapsed or refractory multiple myeloma. Eur J Med Res 2010; 15: 13–19.
   PubMed Web of Science ®Google Scholar
• Pönisch W, Rozanski M, Goldschmidt H, et al. Combined bendamustine, prednisolone and thalidomide for refractory or relapsed multiple myeloma after autologous stem-cell transplantation or conventional chemotherapy: results of a Phase I clinical trial. Br J Haematol 2008; 143: 191–200.
   PubMed Web of Science ®Google Scholar
• Pönisch W, Bourgeois M, Moll B, et al. Combined bendamustine, prednisone and bortezomib (BPV) in patients with relapsed or refractory multiple myeloma. J Cancer Res Clin Oncol 2013; 139: 499–508.
   PubMed Web of Science ®Google Scholar
• Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia 2012; 26: 149–157.
   PubMed Web of Science ®Google Scholar
• Vij R. Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. Oncology (Williston Park) 2011; 25(Suppl. 2): 45–55.
   PubMedGoogle Scholar
• Grzasko N, Morawska M, Hus M. Optimizing the treatment of patients with multiple myeloma and renal impairment. Clin Lymphoma Myeloma Leuk 2014; 15: 187–198.
   PubMed Web of Science ®Google Scholar
• Pönisch W, Andrea M, Wagner I, et al. Successful treatment of patients with newly diagnosed/untreated multiple myeloma and advanced renal failure using bortezomib in combination with bendamustine and prednisone. J Cancer Res Clin Oncol 2012; 138: 1405–1412.
   PubMed Web of Science ®Google Scholar
• Pönisch W, Moll B, Bourgeois M, et al. Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with relapsed or refractory multiple myeloma and light chain-induced renal failure. J Cancer Res Clin Oncol 2013; 139: 1937–1946.
   PubMed Web of Science ®Google Scholar
• Mark TM, Reid W, Niesvizky R, et al. A phase 1 study of bendamustine and melphalan conditioning for autologous stem cell transplantation in multiple myeloma. Biol Blood Marrow Transplant 2013; 19: 831–837.
   PubMed Web of Science ®Google Scholar
• Burotto M, Stetler-Stevenson M, Arons E, et al. Bendamustine and rituximab in relapsed and refractory hairy cell leukemia. Clin Cancer Res 2013; 19: 6313–6321.
   PubMed Web of Science ®Google Scholar
• Fowler N, Kahl BS, Lee P, et al. Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. J Clin Oncol 2011; 29: 3389–3395.
   PubMed Web of Science ®Google Scholar
• Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006; 24: 3187–3205.
   PubMed Web of Science ®Google Scholar
• Cheson BD, Kroll ML. Bendamustine induced neurotoxicity. Clin Adv Hematol Oncol 2009; 7: 743–746.
   PubMedGoogle Scholar
• Owen JS, Melhem M, Passarell JA, et al. Bendamustine pharmacokinetic profile and exposure-response relationships in patients with indolent non-Hodgkin's lymphoma. Cancer Chemother Pharmacol 2010; 66: 1039–1049.
   PubMed Web of Science ®Google Scholar
• Fischer K, Cramer P, Stilgenbauer S, et al. Bendamustine combined with Rituximab (BR) in first-line therapy of advanced CLL: a multicenter phase II trial of the German CLL Study Group (GCLLSG). Blood 2009; 114: 205.
   Google Scholar
• Dubbelman AC, Rosing H, Darwish M, et al. Pharmacokinetics and excretion of 14C-bendamustine in patients with relapsed or refractory malignancy. Drugs R D 2013; 13: 17–28.
   PubMedGoogle Scholar
• Preiss R, Teichert J, Athmani A, et al. [poster]. 2nd International Conference on Drug Discovery and Therapy; 2010 Feb 1–4; Dubai.
   Google Scholar
• Mundipharma. Levact® (bendamustine) Summary of product characteristics. Available from: http://www.medicines.ie/medicine/14828/SPC/Levact+25mg+and+100+mg++powder+for+concentrate+for+solution+for+infusion/.
   Google Scholar
• Goede V, Fischer K, Busch R, et al. Chemoimmunotherapy with GA101 plus chlorambucil in patients with chronic lymphocytic leukemia and comorbidity: results of the CLL11 (BO21004) safety run-in. Leukemia 2013; 27: 1172–1174.
   PubMed Web of Science ®Google Scholar
• Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014; 371: 213–223.
   PubMed Web of Science ®Google Scholar
• O’Brien S, Furman RR, Coutre SE, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol 2014; 15: 48–58.
   PubMed Web of Science ®Google Scholar
• Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 2014; 370: 997–1007.
   PubMed Web of Science ®Google Scholar