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Zevalin Safe, Effective in NHL Patients After Previous Radiotherapy

Zevalin Safe, Effective in NHL Patients After Previous Radiotherapy

NEW ORLEANS—Treatment
with the radioimmunotherapy drug ibritumo-mab tiuxetan (Zevalin) appears to be
safe and effective for patients with some of the most common types of non-Hodg-kin’s
lymphoma (NHL) who have received prior external beam radiotherapy, Roger M.
Macklis, MD, said at the 44th Annual Meeting of the American Society for
Therapeutic Radiology and Oncology (ASTRO abstract 240).

The results of the retrospective study are encouraging for
investigators who hope that the combination is radiosyn-ergistic and might
allow expansion of the patient population who can benefit from Zev-alin therapy
by permitting lower effective doses, said Dr. Macklis, chair of the Department
of Radiation Oncology, Cleveland Clinic Foundation, and lead investigator of
the study.

Zevalin consists of a murine monoclonal antibody (ibritumomab)
bound to a radioactive isotope (yttrium-90) by a strong linking agent (tiuxetan).
The antibody targets the CD20 antigen on the surface of mature B cells and
B-cell tumors.

The researchers analyzed database information on 211
patients registered in Zevalin clinical trials: 60 patients who had received
prior external beam radiotherapy and 151 patients who had not. "There is no
evidence at this point of an increased response or increased adverse events in
patients who received Zevalin after prior radiation," Dr. Macklis said.

There was no significant difference in the incidence of
grade 3-4 adverse events for patients with or without prior radiotherapy. There
was a suggestion of an increased risk of grade 3-4 adverse events in the
central nervous and respiratory systems (P = .07) with previous
radiotherapy. However, the investigators dismissed even this nonsignificant
increase because some of the patients with these adverse events had not
received prior radiotherapy to the areas in question.

The study was inspired by observations in Dr. Macklis’ lab
that relatively low doses of ionizing radiation increased CD20+ surface
expression by 35% to 45% in a panel of human B-cell lines. The next question is
whether this in vitro finding of CD20+ surface antigen radio-induction can be
used clinically.

Zevalin’s dose-limiting toxicity, involving hematopoietic
suppression and thrombocytopenia, make depressed bone marrow reserves an
important factor for appropriate patient selection. Mechanisms to amplify
antibody targeting and CD20+ surface antigen expression could potentially allow
groups of currently ineligible patients to receive this treatment at lower but
still effective doses.

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