Opinion statement
The clinical development and US Food and Drug Administration approval in 1997 of the monoclonal anti-CD20 antibody rituximab have been major treatment advances for patients with B-cell non-Hodgkin’s lymphoma (NHL). Rituximab produces responses in approximately 50% of cases of relapsed, low grade NHL. Most of these responses are partial remissions; cure remains elusive. One way to enhance the effectiveness of monoclonal antibodies is to chelate radionuclides such as yttrium-90 (90Y) to the antibody. 90Y is a high-energy, beta-emitting radioisotope that delivers most of its radiation over a path length of 2 to 5 mm. Therefore, the antibody delivers, or targets, the radiation only to CD20+ cells, sparing normal cells from the radiation. Ibritumomab is the murine anti-CD20 antibody that was engineered to develop the human chimeric antibody rituximab. Tiuxetan is a linker/chelator that is attached to the antibody to form ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals, San Diego, CA). Zevalin can be reacted with 111indium (111In) for imaging and 90Y for therapy. Phase I studies of Zevalin have determined that patients with a baseline platelet count greater than 150,000 × 106/L receive 0.4 mCi/kg. Patients with a platelet count of 100 to 149,000 × 106/L should receive 0.3 mCi/kg. Zevalin has a higher overall response rate (ORR) than its cold antibody counterpart rituximab, as demonstrated in two separate clinical trials. The first trial (IDEC 106-04) randomized 143 rituximab-naïve patients with relapsed NHL to receive rituximab or Zevalin. The ORR for Zevalin was 80% compared with 56% for rituximab (P = 0.002). The second trial (IDEC 106-06) tested the efficacy of Zevalin in patients who were rituxanrefractory; the ORR was 74%. The main toxicity of Zevalin was reversible myelosuppression. These studies indicate that radiolabeled anti-CD20 antibodies can produce a higher ORR than rituximab. Single-dose Zevalin is another treatment alternative for patients with relapsed low grade NHL. It is well-tolerated even by older adults. The exact role of Zevalin in the therapy of NHL is undetermined. New studies are underway to explore whether patients can safely receive a second dose of Zevalin and to combine Zevalin with highdose chemotherapy and stem cell rescue. The outcome of these studies will be helpful in deciding how best to integrate this new modality into the treatment paradigm of NHL.
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References and Recommended Reading
Dinse GE, Umbach DM, Sasco AJ, Hoel DG, Davis DL: Unexplained increases in cancer incidence in the United States from 1975 to 1994: possible sentinel health indicators. Annu Rev Public Health 1999, 20:173–209.
Grillo-Lopez AJ, White CA, Varns C, et al.: Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma [review]. Semin Oncol 1999, 26:66–73.
Maloney DG, Liles TM, Czerwinski DK, et al.: Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDECC2B8) in patients with recurrent B-cell lymphoma. Blood 1994, 84:2457–2466.
McLaughlin P, Grillo-Lopez 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, 16:2825–2833.
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, 17:268–276.
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, 346:235–242.
DeNardo GL, DeNardo SJ, Goldstein DS, et al.: Maximum-tolerated dose, toxicity, and efficacy of (131)I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin’s lymphoma. J Clin Oncol 1998, 16:3246–3256.
DeNardo SJ, DeNardo GL, Kukis DL, et al.: 67Cu-2IT-BAT-Lym-1 pharmacokinetics, radiation dosimetry, toxicity and tumor regression in patients with lymphoma. J Nuclear Med 1999, 40:302–310.
Kaminski MS, Zasadny KR, Francis IR, et al.: Radioimmunotherapy of B-cell lymphoma with [131I] anti-B1 anti-CD20) antibody. N Engl J Med 1993, 329:459–465.
Kaminski M, Estes J, Zasadny K, et al.: Radioimmunotherapy with iodine 131I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. Blood 2000, 96:1259–1266.
Vose JM, Wahl RL, Saleh M, et al.: Multicenter phase II study of iodine-131 tositumomab for chemotherapyrelapsed/ refractory low-grade and transformed low-grade B-cell non-Hodgkin’s lymphomas. J Clin Oncol 2000, 18:1316–1323.
Vose JM, Colcher D, Gobar L, et al.: Phase I/II trial of multiple dose 131Iodine-MAb LL2 (CD22) in patients with recurrent non-Hodgkin’s lymphoma. Leuk Lymphoma 2000, 38:91–101.
Liu SY, Eary JF, Petersdorf SH, et al.: Follow-up of relapsed B-cell lymphoma patients treated with iodine-131labeled anti-CD20 antibody and autologous stem-cell rescue. J Clin Oncol 1998, 16:3270- 3278.
Press O, Eary J, Liu S, et al.: A phase I/II trial of high dose iodine-131anti-B1 (anti-CD20) monoclonal antibody, etoposide, cyclophosphamide, and autologous stem cell transplantation for patients with relapsed B cell lymphomas. Proc Am Soc Clin Oncol 1998, 17:3a.
Press OW: Radiolabeled antibody therapy of B-cell lymphomas [review]. Semin Oncol 1999, 26:58–65.
Knox SJ, Goris ML, Trisler K, et al.: Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma. Clin Cancer Res 1996, 2:457–470.
Witzig TE, White CA, Wiseman GA, et al.: Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin’s lymphoma. J Clin Oncol 1999, 17:3793–3803.
Wiseman G, White C, Stabin M, et al.: Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin’s lymphoma. Eur J Nucl Med 2000, 27:766–777.
Witzig T, Gordon L, Wiseman G, et al.: Reduced dose Zevalin is safe and effective in patients with relapsed or refractory low grade follicular or CD20+ transformed B cell non-Hodgkin’s lymphoma and mild thrombocytopenia. Blood 2000, 96:728a.
Witzig Te, White Ca, Gordon L, et al.: Response to Zevalin is superior to response to rituximab regardless of age and extent of disease. Proc ASCO 2001, 20:279a.
Witzig T, White C, Flinn I, et al.: Zevalin radioimmunotherapy of rituximab-refractory follicular non-Hodgkin’s lymphoma. Blood 2000, 96:507a.
Witzig TE, Wiseman G: Clinical development of 90yttrium-conjugated murine anti-CD20 radioimmunoconjugates (90Y-ibritumomab tiuxetan, 90Y-Zevalin) for B-cell non-Hodgkin’s lymphomas. In Monoclonal Antibody Therapy of Hematologic Malignancies, edn 1. Edited by Cheson B. Abingdon, UK: Darwin Scientific Publishing Limited; 2001:203–214.
Press O, Eary J, Gooley T, et al.: A phase I/II trial of iodine-131tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas. Blood 2000, 96:2934–2942.
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, 19:389–397.
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Alcindor, T., Witzig, T.E. Radioimmunotherapy with Yttrium-90 Ibritumomab tiuxetan for patients with relapsed cd20+ B-Cell non-Hodgkin’s Lymphoma. Curr. Treat. Options in Oncol. 3, 275–282 (2002). https://doi.org/10.1007/s11864-002-0027-y
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DOI: https://doi.org/10.1007/s11864-002-0027-y