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Update on the rational use of Y-ibritumomab tiuxetan in the treatment of follicular lymphoma.

ABSTRACT: The development of radiolabeled antibodies against CD20 has facilitated targeted treatment of follicular lymphoma (FL). By using (90)Y-ibritumomab tiuxetan (Zevalin((R))), a radionuclide (yttrium-90, linked by the chelator tiuxetan to the antibody ibritumomab) is brought into the vicinity of lymphoma cells. By the so-called cross-fire effect, this beta emitter has the capacity to destroy not only the lymphoma cells having bound the antibody, but also neighboring lymphoma cells. Currently this antibody is licensed in the European Union for use in relapsed or refractory FL. It is anticipated that this drug will also be approved for use as consolidation therapy after successful first-line treatment. Here we first will review the published literature supporting the use of (90)Y-ibritumomab tiuxetan in the aforementioned indications and emerging data showing applicability of ibritumomab tiuxetan as sole first-line therapy for FL, as well as in the transplant setting. Possible strategies of incorporating ibritumomab tiuxetan into the treatment algorithm of FL are discussed.

SUBMITTER: Lehnert M

PROVIDER: S-EPMC2886339 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Update on the rational use of Y-ibritumomab tiuxetan in the treatment of follicular lymphoma.

Lehnert Martina M Ludwig Heinz H Zojer Niklas N

OncoTargets and therapy 20090218

The development of radiolabeled antibodies against CD20 has facilitated targeted treatment of follicular lymphoma (FL). By using (90)Y-ibritumomab tiuxetan (Zevalin((R))), a radionuclide (yttrium-90, linked by the chelator tiuxetan to the antibody ibritumomab) is brought into the vicinity of lymphoma cells. By the so-called cross-fire effect, this beta emitter has the capacity to destroy not only the lymphoma cells having bound the antibody, but also neighboring lymphoma cells. Currently this an ...[more]

PMID: 20616907

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Project description:PurposeThe main drawbacks of radioimmunotherapy have been severe hematological toxicity and potential development of myelodysplastic syndrome and secondary leukemia. Activation of p53 follows a major pathway by which normal tissues respond to DNA-damaging agents, such as chemotherapy and radiation therapy, that result in injuries and pathological consequences. This pathway is separate from the tumor suppressor pathway of p53. We have previously reported that use of low-dose arsenic (LDA) temporarily and reversibly suppresses p53 activation, thereby ameliorating normal tissue toxicity from exposure to 5-fluorouracil and X rays. We have also demonstrated that LDA-mediated protection requires functional p53 and thus is selective to normal tissues, as essentially every cancer cell has dysfunctional p53. Here we tested the protective efficacy of LDA for bone marrow tissue against radioimmunotherapy through animal experiments.Methods and materialsMice were subjected to LDA pretreatment for 3 days, followed by treatment with Y-90 ibritumomab tiuxetan. Both dose course (10, 25, 50, 100, and 200 μCi) and time course (6, 24, and 72 hours and 1 and 2 weeks) experiments were performed. The response of bone marrow cells to LDA was determined by examining the expression of NFκB, Glut1, and Glut3. Staining with hematoxylin and eosin, γ-H2AX, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to examine morphology, DNA damage response, and apoptotic cell populations.ResultsElevated levels of NFκB, Glut1, and Glut3 were observed in bone marrow cells after LDA treatment. Bone marrow damage levels induced by Y-90 ibritumomab tiuxetan were greatly reduced by LDA pretreatment. Consistent with this observation, significantly less DNA damage and fewer apoptotic cells were accumulated after Y-90 ibritumomab tiuxetan treatment in LDA-pretreated mice. Furthermore, in the mouse xenograft model implanted with human Karpas-422 lymphoma cells, LDA pretreatment did not have any detectable effect on either tumor growth or Y-90 ibritumomab tiuxetan (200 μCi)-induced tumor suppression.ConclusionsLDA pretreatment protected bone marrow without compromising tumor control caused by Y-90 ibritumomab tiuxetan.

Dataset Information

Update on the rational use of Y-ibritumomab tiuxetan in the treatment of follicular lymphoma.

Publications

Update on the rational use of Y-ibritumomab tiuxetan in the treatment of follicular lymphoma.

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