BioDrugs

, Volume 26, Issue 2, pp 71–82 | Cite as

Rituximab

Current Status as Therapy for Malignant and Benign Hematologic Disorders
  • Nihal E. Abdulla
  • Mary J. Ninan
  • Avi B. Markowitz
Review Article

Abstract

Rituximab is a chimeric monoclonal antibody targeting the pan-B-cell antigen CD20 and was the first monoclonal antibody approved for clinical use in the treatment of cancer. Since its first approval by the FDA in 1997, investigators have continued to explore a variety of clinical conditions in which rituximab has proven effective with minimal toxicity. Rituximab, as monotherapy or in combination with chemotherapy, has been studied extensively in untreated and relapsed/refractory settings as both induction and maintenance therapy for the treatment of CD20-positive lymphomas and chronic lymphocytic leukemia, in addition to non-malignant hematologic disorders including autoimmune hemolytic anemia and immune thrombo-cytopenic purpura. Here we discuss the clinical development of rituximab with a review of the efficacy data from clinical trials and its current status in the practice of hematology and oncology.

Notes

Acknowledgments

The authors are solely responsible for the development and writing of the manuscript. Genentech, Inc provided support only for third-party editorial assistance for this manuscript. A.B. Markowitz has served as a consultant and/or Speakers Bureau for Genentech, Inc.

Both N.E. Abdulla and M.J. Ninan contributed equally to the manuscript.

References

  1. 1.
    Olszewski AJ, Grossbard ML. Empowering targeted therapy: lessons from rituximab. Sci STKE 2004; 2004 (241): pe30PubMedGoogle Scholar
  2. 2.
    Deans JP, Kalt L, Ledbetter JA, et al. Association of 75/80-kDa phosphoproteins and the tyrosine kinases Lyn, Fyn, and Lck with the B cell molecule CD20. Evidence against involvement of the cytoplasmic regions of CD20. J Biol Chem 1995; 270 (38): 22632–8PubMedCrossRefGoogle Scholar
  3. 3.
    Pedersen IM, Buhl AM, Klausen P, et al. The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated protein-kinase-dependent mechanism. Blood 2002; 99 (4): 1314–9PubMedCrossRefGoogle Scholar
  4. 4.
    Stashenko P, Nadler LM, Hardy R, et al. Characterization of a human B lymphocyte-specific antigen. J Immunol 1980; 125 (4): 1678–85PubMedGoogle Scholar
  5. 5.
    Smith MR. Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene 2003; 22 (47): 7359–68PubMedCrossRefGoogle Scholar
  6. 6.
    Wood AM. Rituximab: an innovative therapy for non-Hodgkin’s lymphoma. Am J Health Syst Pharm 2001; 58 (3): 215–29; quiz 230-2PubMedGoogle Scholar
  7. 7.
    Friedberg JW. Unique toxicities and resistance mechanisms associated with monoclonal antibody therapy. Hematology Am Soc Hematol Educ Program 2005: 329-34Google Scholar
  8. 8.
    Casak SJ, Lemery SJ, Shen YL, et al. U.S. Food and Drug Administration approval: rituximab in combination with fludarabine and cyclophosphamide for the treatment of patients with chronic lymphocytic leukemia. Oncologist 2011; 16 (1): 97–104PubMedCrossRefGoogle Scholar
  9. 9.
    McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998; 16 (8): 2825–33PubMedGoogle Scholar
  10. 10.
    European Medicines Agency. European Public Assessment Report (EPAR) for MabThera [online]. Available from URL: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000165/human_med_000897.jsp&murl=menus/medicines/medicines.jsp&mid=WC0b01ac058001d125 [Accessed 2011 May 4]
  11. 11.
    Jaffe E, Harris N, Stein H. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon, France: IARC Press, 2001Google Scholar
  12. 12.
    National Cancer Institute. Surveillance epidemiology and end results stat fact sheets. Cancer: chronic lymphocytic leukemia [online]. Available from URL: seer.cancer.gov/statfacts/html/clyl.html [Accessed 2012 Jan 22]Google Scholar
  13. 13.
    Howlader N, Noone A, Krapcho M, et al. SEER cancer statistics review, 1975–2008. Bethesda, MD: National Cancer Institute [online]. Available from URL: http://seer.cancer.gov/csr/1975_2008/ based on November 2010 SEER data submission, posted to the SEER website, 2011 [Accessed 2012 Jan 12]
  14. 14.
    Maddocks K, Lin T. Update in the management of chronic lymphocytic leukemia. J Hematol Oncol 2009; 2: 29PubMedCrossRefGoogle Scholar
  15. 15.
    Cheson B, Bennett J, Grever M, et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996; 87 (12): 4990–7PubMedGoogle Scholar
  16. 16.
    Hallek M, Cheson B, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111 (12): 5446–56CrossRefGoogle Scholar
  17. 17.
    Rai K, Peterson B, Appelbaum F, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 2000; 343 (24): 1750–7PubMedCrossRefGoogle Scholar
  18. 18.
    Leporrier M, Chevret S, Cazin B, et al. Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients. Blood 2001; 98 (8): 2319–25PubMedCrossRefGoogle Scholar
  19. 19.
    Rai K, Peterson B, Appelbaum F, et al. Long-term survival analysis of the North American Intergroup Study C9011 comparing fludarabine (F) and chlorambucil (C) in previously untreated patients with chronic lymphocytic leukemia (CLL) [abstract]. Blood 2009; 114 (22): A–536Google Scholar
  20. 20.
    O’Brien S, Kantarjian H, Thomas D, et al. Rituximab dose-escalation trial in chronic lymphocytic leukemia. J Clin Oncol 2001; 19 (8): 2165–70PubMedGoogle Scholar
  21. 21.
    Hainsworth J, Litchy S, Barton J, et al. Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2003; 21 (9): 1746–51PubMedCrossRefGoogle Scholar
  22. 22.
    Byrd J, Murphy T, Howard R, et al. Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. J Clin Oncol 2001; 19 (8): 2153–64PubMedGoogle Scholar
  23. 23.
    Berinstein N, Grillo-López A, White C, et al. Association of serum rituximab (IDEC-C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin’s lymphoma. Ann Oncol 1998; 9 (9): 995–1001PubMedCrossRefGoogle Scholar
  24. 24.
    Thomas DA, O’Brien S, Giles FJ, et al. Single-agent rituximab in early-stage chronic lymphocytic leukemia [abstract]. Blood 2001; 98: 1533Google Scholar
  25. 25.
    McLaughlin P, White CA, Grillo-López AJ, et al. Clinical status and optimal use of rituximab for B-cell lymphomas. Oncology 1998; 12 (12): 1763–9; discussion 1769-70, 1775-7PubMedGoogle Scholar
  26. 26.
    Ladetto M, Bergui L, Ricca I, et al. Rituximab anti-CD20 monoclonal antibody induces marked but transient reductions of peripheral blood lymphocytes in chronic lymphocytic leukaemia patients. Med Oncol 2000; 17 (3): 203–10PubMedCrossRefGoogle Scholar
  27. 27.
    Gentile M, Vigna E, Mazzone C, et al. Rituximab for the treatment of patients with chronic lymphocytic leukemia. Cancer Manag Res 2010; 2: 71–81PubMedGoogle Scholar
  28. 28.
    Byrd J, Peterson B, Morrison V, et al. Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712). Blood 2003; 101 (1): 6–14PubMedCrossRefGoogle Scholar
  29. 29.
    Byrd J, Rai K, Peterson B, et al. Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood 2005; 105 (1): 49–53PubMedCrossRefGoogle Scholar
  30. 30.
    Keating M, O’Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol 2005; 23 (18): 4079–88PubMedCrossRefGoogle Scholar
  31. 31.
    Wierda W, O’Brien S, Wen S, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol 2005; 23 (18): 4070–8PubMedCrossRefGoogle Scholar
  32. 32.
    Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010; 376 (9747): 1164–74PubMedCrossRefGoogle Scholar
  33. 33.
    Robak T, Dmoszynska A, Solal-Céligny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol 2010; 28 (10): 1756–65PubMedCrossRefGoogle Scholar
  34. 34.
    Rummel M. Reassessing the standard of care in indolent lymphoma: a clinical update to improve clinical practice. J Natl Compr Canc Netw 2010; 8Suppl. 6: S1–14; quiz S15PubMedGoogle Scholar
  35. 35.
    Kay N, Geyer S, Call T, et al. Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia. Blood 2007; 109 (2): 405–11PubMedCrossRefGoogle Scholar
  36. 36.
    Kay N, Wu W, Kabat B, et al. Pentostatin and rituximab therapy for previously untreated patients with B-cell chronic lymphocytic leukemia. Cancer 2010; 116 (9): 2180–7PubMedGoogle Scholar
  37. 37.
    Reynolds C, Bella ND, Lyons RM, et al. Phase III trial of fludarabine, cyclophosphamide, and rituximab vs. pentostatin, cyclophosphamide, and rituximab in B-cell chronic lymphocytic leukemia [abstract no. 327]. Blood (ASH Annual Meeting Abstracts) 2008; 112Google Scholar
  38. 38.
    Aivado M, Schulte K, Henze L, et al. Bendamustine in the treatment of chronic lymphocytic leukemia: results and future perspectives. Semin Oncol 2002; 29 (4 Suppl. 13): 19–22PubMedCrossRefGoogle Scholar
  39. 39.
    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 (27): 4473–9PubMedCrossRefGoogle Scholar
  40. 40.
    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) [abstract]. Blood 2009; 114 (22): 205Google Scholar
  41. 41.
    Chow KU, Kim SZ, von Neuhoff N, et al. Clinical efficacy of immuno-chemotherapy with fludarabine, epirubicin and rituximab in the treatment for chronic lymphocytic leukaemia and prolymphocytic leukaemia. Eur J Haematol 2011; 87 (5): 426–33PubMedCrossRefGoogle Scholar
  42. 42.
    Del Poeta G, Del Principe MI, Buccisano F, et al. Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia. Cancer 2008; 112 (1): 119–28CrossRefGoogle Scholar
  43. 43.
    BoschF, Villamor N, Abrisqueta P, et al. Rituximab maintenance in patients with chronic lymphocytic leukemia (CLL) sustains the response obtained after first-line treatment with rituximab plus fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) [abstract no. 1382]. Blood (ASH Annual Meeting Abstracts) 2010; 116Google Scholar
  44. 44.
    Hainsworth JD. First-line and maintenance treatment with rituximab for patients with indolent non-Hodgkin’s lymphoma. Semin Oncol 2003; 30 (1 Suppl. 2): 9–15PubMedCrossRefGoogle Scholar
  45. 45.
    Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab is superior in respect of progression free survival and CR rate when compared to CHOP plus rituximab as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: final results of a randomized phase III study of the StiL (Study Group Indolent Lymphomas, Germany) [abstract no. 405]. Blood 2009; 114: 168Google Scholar
  46. 46.
    HillmenP, Gribben JG, Follows GA, et al. Rituximab plus chlorambucil in patients with CD20-positive B-cell chronic lymphocytic leukemia (CLL): final response analysis of an open-label phase II study [abstract no. 697]. Blood 2010; 116 (21)Google Scholar
  47. 47.
    Faderl S, Ferrajoli A, Wierda W, et al. Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence. Cancer 2010; 116 (10): 2360–5PubMedGoogle Scholar
  48. 48.
    Zent CS, Call TG, Shanafelt TD, et al. Early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. Cancer 2008; 113 (8): 2110–8PubMedCrossRefGoogle Scholar
  49. 49.
    Czuczman MS. Controversies in follicular lymphoma: “who, what, when, where, and why?” (not necessarily in that order!). Hematology Am Soc Hematol Educ Program 2006: 303-10Google Scholar
  50. 50.
    A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project. Blood 1997; 89 (11): 3909–18Google Scholar
  51. 51.
    Horning SJ. Natural history of and therapy for the indolent non-Hodgkin’s lymphomas. Semin Oncol 1993; 20 (5 Suppl. 5): 75–88PubMedGoogle Scholar
  52. 52.
    Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin’s lymphomas. N Engl J Med 1984; 311 (23): 1471–5PubMedCrossRefGoogle Scholar
  53. 53.
    Marcus R, Imrie K, Solal-Celigny P, et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol 2008; 26 (28): 4579–86PubMedCrossRefGoogle Scholar
  54. 54.
    Schulz H, Bohlius JF, Trelle S,et al. Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: a systematic review and meta-analysis. J Natl Cancer Inst 2007; 99 (9): 706–14PubMedCrossRefGoogle Scholar
  55. 55.
    Rummel M, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab is superior in respect of progression free survival and CR rate when compared to CHOP plus rituximab as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: final results of a randomized phase III study of the StiL (Study Group Indolent Lymphomas, Germany) [abstract no. 6]. Blood (ASH Annual Meeting Abstracts) 2010; 116Google Scholar
  56. 56.
    Salles G, Mounier N, de Guibert S, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood 2008; 112 (13): 4824–31PubMedCrossRefGoogle Scholar
  57. 57.
    Herold M, Haas A, Srock S, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 2007; 25 (15): 1986–92PubMedCrossRefGoogle Scholar
  58. 58.
    Hiddemann W, Kneba M, Dreyling M, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005; 106 (12): 3725–32PubMedCrossRefGoogle Scholar
  59. 59.
    Witzig TE, Vukov AM, Habermann TM, et al. Rituximab therapy for patients with newly diagnosed, advanced-stage, follicular grade I non-Hodgkin’s lymphoma: a phase II trial in the North Central Cancer Treatment Group. J Clin Oncol 2005; 23 (6): 1103–8PubMedCrossRefGoogle Scholar
  60. 60.
    Colombat P, Salles G, Brousse N, et al. Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation. Blood 2001; 97 (1): 101–6PubMedCrossRefGoogle Scholar
  61. 61.
    Czuczman MS, Grillo-Lopez AJ, White CA, et al. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol 1999; 17 (1): 268–76PubMedGoogle Scholar
  62. 62.
    Czuczman MS, Weaver R, Alkuzweny B, et al. Prolonged clinical and molecular remission in patients with low-grade or follicular non-Hodgkin’s lymphoma treated with rituximab plus CHOP chemotherapy: 9-year follow-up. J Clin Oncol 2004; 22 (23): 4711–6PubMedCrossRefGoogle Scholar
  63. 63.
    Ardeshna K, Qian W, Smith P, et al. An intergroup randomised trial of rituximab versus a watch and wait strategy in patients with stage II, III, IV, asymptomatic, non-bulky follicular lymphoma (Grades 1, 2 and 3a): a preliminary analysis [abstract no. 6]. Blood (ASH Annual Meeting Abstracts) 2010; 116Google Scholar
  64. 64.
    van Oers MH, Klasa R, Marcus RE, et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood 2006; 108 (10): 3295–301PubMedCrossRefGoogle Scholar
  65. 65.
    Rummel M, Kaiser U, 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) [abstract no. 856]. Blood (ASH Annual Meeting Abstracts) 2010; 116Google Scholar
  66. 66.
    Salles G, Seymour JF, Offner F, et al. 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 2011; 377 (9759): 42–51PubMedCrossRefGoogle Scholar
  67. 67.
    Martinelli G, Schmitz SF, Utiger U, et al. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol 2010; 28 (29): 4480–4PubMedCrossRefGoogle Scholar
  68. 68.
    Hochster H, Weller E, Gascoyne RD, et al. Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. J Clin Oncol 2009; 27 (10): 1607–14PubMedCrossRefGoogle Scholar
  69. 69.
    van Oers MH, Van Glabbeke M, Giurgea L, 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 (17): 2853–8PubMedCrossRefGoogle Scholar
  70. 70.
    Pettengell R, Schmitz N, Gisselbrecht D, et al. Randomized study of rituximab in patients with relapsed or resistant follicular lymphoma prior to high-dose therapy as in vivo purging and to maintain remission following high-dose therapy [abstract no. 8005]. J Clin Oncol 2010; 28 Suppl. 15sGoogle Scholar
  71. 71.
    Forstpointner R, Unterhalt M, Dreyling M, et al. 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 2006; 108 (13): 4003–8PubMedCrossRefGoogle Scholar
  72. 72.
    Hainsworth JD, Litchy S, Shaffer DW, et al. Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin’s lymphoma-a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2005; 23 (6): 1088–95PubMedCrossRefGoogle Scholar
  73. 73.
    Habermann TM, Weller EA, Morrison VA, et al. Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 2006; 24 (19): 3121–7PubMedCrossRefGoogle Scholar
  74. 74.
    Groves FD, Linet MS, Travis LB, et al. Cancer surveillance series: non-Hodgkin’s lymphoma incidence by histologic subtype in the United States from 1978 through 1995. J Natl Cancer Inst 2000; 92 (15): 1240–51PubMedCrossRefGoogle Scholar
  75. 75.
    DeVita VT, Canellos GP, Chabner B, et al. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet 1975; 1 (7901): 248–50Google Scholar
  76. 76.
    Miller TP, Dana BW, Weick JK, et al. Southwest Oncology Group clinical trials for intermediate- and high-grade non-Hodgkin’s lymphomas. Semin Hematol 1988; 25 (2 Suppl. 2): 17–22PubMedGoogle Scholar
  77. 77.
    Coltman C, Dahlberg S, Jones S. CHOP is curative in thirty percent of patients with diffuse large cell lymphoma: a twelve year Southwest Oncology Group follow up. Proc Am Soc Clin Oncol 1986; 5: 197Google Scholar
  78. 78.
    Maloney DG, Grillo-López AJ, White CA, et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood 1997; 90 (6): 2188–95PubMedGoogle Scholar
  79. 79.
    Coiffier B, Haioun C, Ketterer N, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood 1998; 92 (6): 1927–32PubMedGoogle Scholar
  80. 80.
    Vose JM, Link BK, Grossbard ML, et al. Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin’s lymphoma. J Clin Oncol 2001; 19 (2): 389–97PubMedGoogle Scholar
  81. 81.
    Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002; 346 (4): 235–42PubMedCrossRefGoogle Scholar
  82. 82.
    Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood 2010; 116 (12): 2040–5PubMedCrossRefGoogle Scholar
  83. 83.
    Link BK, Brooks J, Wright K, et al. Diffuse large B-cell lymphoma in the elderly: diffusion of treatment with rituximab and survival advances with and without anthracyclines. Leuk Lymphoma 2011; 52 (6): 994–1002PubMedCrossRefGoogle Scholar
  84. 84.
    Pfreundschuh M, Kuhnt E, Trümper L, et al. Randomised intergroup trial of first line treatment for young low-risk patients (<61 years) with diffuse large B-cell non-Hodgkin’s lymphoma (DLBCL) with a CHOP-like regimen with or without the anti-CD20 antibody rituximab: 6-year follow-up of the Mint Study of the Mabthera International Trial (MInT) Group [abstract no. 111]. Blood 2010; 116 (ASH Annual Meeting Abstracts)Google Scholar
  85. 85.
    Morrison VA, Hong F, Habermann TM, et al. R-CHOP versus (vs) CHOP followed by maintenance rituximab (MR) vs observation in older diffuse large B-cell lymphoma (DLBCL) patients (pts): long-term follow-up of Intergroup E4494/C9793 [abstract no. 589]. Blood 2010; 116 (ASH Annual Meeting Abstracts)Google Scholar
  86. 86.
    Hainsworth JD, Flinn IW, Spigel DR, et al. Brief-duration rituximab/chemotherapy followed by maintenance rituximab in patients with diffuse large B-cell lymphoma who are poor candidates for R-CHOP chemotherapy: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma Leuk 2010; 10 (1): 44–50PubMedCrossRefGoogle Scholar
  87. 87.
    Gisselbrecht C. Use of rituximab in diffuse large B-cell lymphoma in the salvage setting. Br J Haematol 2008; 143 (5): 607–21PubMedCrossRefGoogle Scholar
  88. 88.
    Vose JM, Zhang MJ, Rowlings PA, et al. Autologous transplantation for diffuse aggressive non-Hodgkin’s lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 2001; 19 (2): 406–13PubMedGoogle Scholar
  89. 89.
    Kewalramani T, Zelenetz AD, Hedrick EE, et al. High-dose chemo-radiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis. Blood 2000; 96 (7): 2399–404PubMedGoogle Scholar
  90. 90.
    Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med 1995; 333 (23): 1540–5PubMedCrossRefGoogle Scholar
  91. 91.
    Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol 2010; 28 (27): 4184–90PubMedCrossRefGoogle Scholar
  92. 92.
    National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology, non-Hodgkin’s lymphoma: V.I.2011 [online]. Available from URL: http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf [Accessed 2011 Jan 1]
  93. 93.
    Romaguera JE, Fayad LE, Feng L, et al. Ten-year follow-up after intense chemoimmunotherapy with Rituximab-HyperCVAD alternating with Rituximab-high dose methotrexate/cytarabine (R-MA) and without stem cell transplantation in patients with untreated aggressive mantle cell lymphoma. Br J Haematol 2010; 150 (2): 200–8PubMedGoogle Scholar
  94. 94.
    Thomas DA. Rituximab as therapy for acute lymphoblastic leukemia. Clin Adv Hematol Oncol 2010; 8 (3): 168–71PubMedGoogle Scholar
  95. 95.
    Fayad L, Thomas D, Romaguera J. Update of the M. D. Anderson Cancer Center experience with hyper-CVAD and rituximab for the treatment of mantle cell and Burkitt-type lymphomas. Clin Lymphoma Myeloma 2007; 8Suppl. 2: S57–62PubMedCrossRefGoogle Scholar
  96. 96.
    Romaguera J, Fayad L, Rodriguez A, et al. Rituximab (R) + Hypercvad alternating with R-methotrexate/cytarabine after 9 years: continued high rate of failure-free survival in untreated mantle cell lymphoma (MCL) [abstract no. 833] Blood 2008 Nov; 112 (ASH Annual Meeting Abstracts)Google Scholar
  97. 97.
    Kenkre VP, Long WL, Eickhoff JC, et al. Maintenance rituximab following induction chemo-immunotherapy for mantle cell lymphoma: long-term follow-up of a pilot study from the Wisconsin Oncology Network. Leuk Lymphoma 2011; 52 (9): 1675–80PubMedCrossRefGoogle Scholar
  98. 98.
    Kluin-Nelemans J, Hoster E, Vehling-Kaiser U, et al. Rituximab maintenance significantly prolongs duration of remission in elderly patients with mantle cell lymphoma. First results of a randomized trial of the European MCL network [abstract no. 0504]. 16th Congress of the European Hematology Association meeting. Haematologica 2011 Jun; 96: 213Google Scholar
  99. 99.
    Griffiths R, Mikhael J, Gleeson M, et al. Addition of rituximab to chemotherapy alone as first-line therapy improves overall survival in elderly patients with mantle cell lymphoma. Blood 2011 Nov; 118 (18): 4808–16PubMedCrossRefGoogle Scholar
  100. 100.
    Parker A, Bowles K, Bradley JA, et al. Management of post-transplant lymphoproliferative disorder in adult solid organ transplant recipients: BCSH and BTS Guidelines. Br J Haematol 2010; 149 (5): 693–705PubMedCrossRefGoogle Scholar
  101. 101.
    Evens AM, David KA, Helenowski I, et al. Multicenter analysis of 80 solid organ transplantation recipients with post-transplantation lymphoproliferative disease: outcomes and prognostic factors in the modern era. J Clin Oncol 2010; 28 (6): 1038–46PubMedCrossRefGoogle Scholar
  102. 102.
    Gatter K, Pezzella F. Diffuse large B-cell lymphoma. Diagn Histopathol 2010; 16 (2): 69–81CrossRefGoogle Scholar
  103. 103.
    Rieger M, Osterborg A, Pettengell R, et al. Primary mediastinal B-cell lymphoma treated with CHOP-like chemotherapy with or without rituximab: results of the Mabthera International Trial Group study. Ann Oncol 2011; 22 (3): 664–70PubMedCrossRefGoogle Scholar
  104. 104.
    Dimopoulos MA, Gertz MA, Kastritis E, et al. Update on treatment recommendations from the Fourth International Workshop on Waldenstrom’s Macroglobulinemia. J Clin Oncol 2009; 27 (1): 120–6PubMedCrossRefGoogle Scholar
  105. 105.
    Ansell SM, Kyle RA, Reeder CB, et al. Diagnosis and management of Waldenström macroglobulinemia: Mayo stratification of macroglobulinemia and risk-adapted therapy (mSMART) guidelines. Mayo Clin Proc 2010; 85 (9): 824–33PubMedCrossRefGoogle Scholar
  106. 106.
    Tsimberidou AM, Catovsky D, Schlette E, et al. Outcomes in patients with splenic marginal zone lymphoma and marginal zone lymphoma treated with rituximab with or without chemotherapy or chemotherapy alone. Cancer 2006; 107 (1): 125–35PubMedCrossRefGoogle Scholar
  107. 107.
    Saini KS, Azim HA, Cocorocchio E, et al. Rituximab in Hodgkin lymphoma: is the target always a hit? Cancer Treat Rev 2011; 37 (5): 385–90PubMedCrossRefGoogle Scholar
  108. 108.
    Maeda LS, Advani RH. The emerging role for rituximab in the treatment of nodular lymphocyte predominant Hodgkin lymphoma. Curr Opin Oncol 2009; 21 (5): 397–400PubMedCrossRefGoogle Scholar
  109. 109.
    Horning S, Bartlett N, Breslin S. Results of a prospective phase II trial of limited and extended rituximab in nodular lymphocyte-predominant Hodgkin’s disease. ASH Annual Meeting Abstracts. Blood 2007; 110: 644Google Scholar
  110. 110.
    Azim HA, Pruneri G, Cocorocchio E, et al. Rituximab in lymphocyte-predominant Hodgkin disease. Oncology 2009; 76 (1): 26–9PubMedCrossRefGoogle Scholar
  111. 111.
    Ekstrand BC, Lucas JB, Horwitz SM, et al. Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood 2003; 101 (11): 4285–9PubMedCrossRefGoogle Scholar
  112. 112.
    Schulz H, Rehwald U, Morschhauser F, et al. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood 2008; 111 (1): 109–11PubMedCrossRefGoogle Scholar
  113. 113.
    Zaja F, Baccarani M, Mazza P, et al. Dexamethasone plus rituximab yields higher sustained response rates than dexamethasone monotherapy in adults with primary immune thrombocytopenia. Blood 2010; 115 (14): 2755–62PubMedCrossRefGoogle Scholar
  114. 114.
    Penalver FJ, Alvarez-Larran A, Diez-Martin JL, et al. Rituximab is an effective and safe therapeutic alternative in adults with refractory and severe autoimmune hemolytic anemia. Ann Hematol 2010; 89 (11): 1073–80PubMedCrossRefGoogle Scholar
  115. 115.
    Zecca M, De Stefano P, Nobili B, et al. Anti-CD20 monoclonal antibody for the treatment of severe, immune-mediated, pure red cell aplasia and hemolytic anemia. Blood 2001; 97 (12): 3995–7PubMedCrossRefGoogle Scholar
  116. 116.
    D’Arena G, Laurenti L, Capalbo S, et al. Rituximab therapy for chronic lymphocytic leukemia-associated autoimmune hemolytic anemia. Am J Hematol 2006; 81 (8): 598–602PubMedCrossRefGoogle Scholar
  117. 117.
    Shanafelt TD, Madueme HL, Wolf RC, et al. Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome. Mayo Clin Proc 2003; 78 (11): 1340–6PubMedCrossRefGoogle Scholar
  118. 118.
    Bussone G, Ribeiro E, Dechartres A, et al. Efficacy and safety of rituximab in adults’ warm antibody autoimmune haemolytic anemia: retrospective analysis of 27 cases. Am J Hematol 2009; 84 (3): 153–7PubMedCrossRefGoogle Scholar
  119. 119.
    de la Rubia J, Moscardo F, Gomez MJ, et al. Efficacy and safety of rituximab in adult patients with idiopathic relapsing or refractory thrombotic thrombocytopenic purpura: results of a Spanish multicenter study. Transfus Apher Sci 2010; 43 (3): 299–303PubMedCrossRefGoogle Scholar
  120. 120.
    Scully M, Cohen H, Cavenagh J, et al. Remission in acute refractory and relapsing thrombotic thrombocytopenic purpura following rituximab is associated with a reduction in IgG antibodies to ADAMTS-13. Br J Haematol 2007; 136 (3): 451–61PubMedCrossRefGoogle Scholar
  121. 121.
    Caramazza D, Quintini G, Abbene I, et al. Rituximab for managing relapsing or refractory patients with idiopathic thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome. Blood Transfus 2010; 8 (3): 203–10PubMedGoogle Scholar
  122. 122.
    Jurgen Barth. Significance of Duration of Maintenance Therapy With Rituximab in Non-Hodgkin Lymphomas (MAINTAIN) [ClinicalTrials.gov identifier NCT00877214]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Jan 12]
  123. 123.
    Rummel MJ, Kaiser U, 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) [abstract no. 856]. Blood 2010 Nov; 116 (ASH Annual Meeting Abstracts)Google Scholar
  124. 124.
    Davis TA, Grillo-López AJ, White CA, et al. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin’s lymphoma: safety and efficacy of re-treatment. J Clin Oncol 2000; 18 (17): 3135–43PubMedGoogle Scholar
  125. 125.
    Olejniczak SH, Hernandez-Ilizaliturri FJ, Clements JL, et al. Acquired resistance to rituximab is associated with chemotherapy resistance resulting from decreased Bax and Bak expression. Clin Cancer Res 2008; 14 (5): 1550–60PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2012

Authors and Affiliations

  • Nihal E. Abdulla
    • 1
  • Mary J. Ninan
    • 1
  • Avi B. Markowitz
    • 1
  1. 1.Division of Hematology/OncologyUniversity of Texas Medical Branch (UTMB)GalvestonUSA

Personalised recommendations