Radioimmunotherapy: An update

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Despite study after study showing the positive, long-term effects achieved through radioimmunotherapy, the treatment has failed to take off in the hematology/oncology field. There are three potential reasons for this. The first two are understandable; that it is very expensive, and that it is only offered in facilities with a nuclear medicine department. The third is inexcusable; that doctors do not suggest radioimmunotherapy to their patients because in many cases it means referring a patient out of their care. For doctors in private practice this negatively affects their bottom line.

What is radioimmunotherapy?

Radioimmunotherapy (RIT) is an anti-cancer treatment in which monoclonal antibodies enter the body, seek out certain cancer cells, and deliver into the cell their payload—a radioactive isotope. It works with the same cell-killing concept as is used in radiation therapy, but with the precision of targeted treatments.

Examples of RIT:

Zevalin
Zevalin uses the monoclonal antibody ibritumomab to track down CD20-expressing B-cells (lymphocytes). The ibritumomab uses the chelator tiuxetan to carry yttrium-90 (Y-90) and indium-111 (In-111) radioactive isotopes to the B-cells (in separate doses), killing them. Zevalin can't distinguish between healthy B-cells and cancerous ones, and it can sometimes damage some nearby cells, but the body can restore B-cells and the surrounding damage is very minimal. Zevalin is FDA approved as a second-line treatment for patients with B-cell follicular lymphoma whose disease is refractory or has relapsed following induction chemotherapy.

Bexxar
Bexxar combines tositumomab and iodine I-131 tositumomab to create a radioactive immunotoxin. The tositumomab tracks down B-cells expressing CD20 in the lymphatic system and kills them by delivering iodine to the cell. Like Zevalin, Bexxar can't distinguish between healthy B-cells and cancerous ones, and it can sometimes damage some nearby cells, but the body can restore B-cells and the surrounding damage is very minimal. Bexxar is FDA approved for patients with follicular lymphoma whose disease has proven refractory to Rituxan and who have relapsed following chemotherapy.

Recent research

Among the emerging research in radioimmunotherapy are two notable studies. The first was presented at the 2010 meeting of the American Society of Clinical Oncology. In it, researchers looked at the efficacy of radioimmunotherapy in the treatment of advanced-stage mantle cell lymphoma. The study looked at 115 patients, most of whom were elderly men. Mantle cell lymphoma was identified only recently and remains poorly understood and therefore the prognosis is typically not good. What this study found was that for this patient population, radioimmunotherapy (specifically Zevalin) was safe, had a low side effect profile, and prolonged survival in a majority of patients treated.

Then in May of 2011 the Journal of Nuclear Medicine published the findings from an extremely small but very compelling study in which 12 patients with indolent, relapsed or refractory non-Hodgkin's lymphoma, and 4 patients with transformed non-Hodgkin lymphoma, were treated with one administration of Zevalin. The patients averaged more than a couple previous chemotherapy or antibody treatments.

The treatment proved largely ineffective for patients with transformed disease. But of the 12 patients with indolent disease, 6 were disease-free almost ten years later, lending plenty of weight to the idea that radioimmunotherapy ought to be considered as a first-line therapy for patients with indolent B-cell lymphomas.

Radioimmunotherapy in current clinical trials

Clinical trials are exploring radioimmunotherapy in a broad array of lymphoma-related applications, including aggressive non-Hodgkin's lymphomas and as a component of stem cell transplantations

One of the hurdles in front of RIT is the fact that it is not approved as a first-line therapy against lymphoma. A European trial recruiting patients right now is testing Zevalin as a first-line therapy. Another clinical trial currently recruiting, this one sponsored by MD Anderson Cancer Center, is examining whether adding Zevalin to standard treatment in autologous stem cell transplantation will be more effective for lymphoma patients.

Meanwhile, researchers at Fred Hutchinson in Washington state are recruiting patients with chronic lymphocytic leukemia (small lymphocytic lymphoma) for a clinical trial using Bexxar as consolidation therapy following chemotherapy—meaning they want to know if Bexxar can wipe out any cancer cells remaining following standard induction therapy. In another trial, this one sponsored by Sidney Kimmel Cancer Center, researchers are exploring the efficacy of Bexxar in certain cases of Hodgkin's lymphoma.

To see clinical trials for Zevalin, click here.
To see clinical trials for Bexxar, click here.

Sources

National Cancer Institute, Radioimmunotherapy

Zevalin.com

Bexxar prescribing information (link to PDF)

Jurczak W et al. Use of radioimmunotherapy for consolidation for chemosensitive mantle cell lymphoma J Clin Oncol 28, 2010 (suppl; abstr e18519).

Buchegger F et al. Six of 12 Relapsed or Refractory Indolent Lymphoma Patients Treated 10 Years Ago with 131 I-Tositumomab Remain in Complete Remission. J Nucl Med June 1, 2011vol. 52 no. 6 896-900.

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