by Janice P. Dutcher, MD
Professor of Medicine at New York Medical College, Associate Director for Clinical Affairs at Our lady of Mercy Comprehensive Cancer Center, Bronx New York
Several new drugs are entering the clinic in the treatment of leukemia and lymphoma.
Of particular interest are the new agents utilizing monoclonial antibody and molecular technology. These techniques produce drugs that go directly to cell targets, like a key in a lock. They are targeted to proteins on the surface of leukemia and lymphoma cells and cause them to die.
Rituxan (Rituximab) is directed to CD20, on the surface of lymphoma cells. Significant anti-lymphoma activity is seen with this antibody in patients with low-grade lymphoma and chronic lymphocytic leukemia, and this is its current clinical use. Rituxan is meeting and exceeding all expectations of activity in killing lymphoma cells and in providing a safe and relatively non-toxic therapy. New studies are evaluating Rituxan in combination with chemotherapy.
Mylotarg (Gemtuzumab Ozogamicin) is a monoclonal antibody directed against CD33 on more than 80% of acute myeloid leukemia cells. Mylotarg has been joined to a toxin, calicheamicin, which acts like chemotherapy. Once the antibody binds to the leukemia cell, the complex enters the cell and the calicheamicin is released and then is able to kill the cell. The agent is effective in killing leukemia cells that are no longer responsive to chemotherapy, because they still carry the CD33 marker.
Campath-1H is approved for treatment of chronic lymphocytic lymphoma. This antibody is directed against CD52, which is almost always present in CLL.
Two radioimmunoconjugates are being evaluated. These are both monoclonal antibodies directed against CD20 on B-cells that are joined to radioactivity to direct the radiation to the lymphoma. Studies with both agents in patients with relapsed lymphoma have demonstrated impressive results in terms of tumor shrinkage.
Bexxar (Tositumomab) is complexed to Iodine-131 which delivers a high dose of radiation to the lymphoma cells. Once the the antibody binds, the radioactivity continues to emit until the cell is killed. This agent requires hospitalization and special precautions, but this approach is highly effective.
Zevalin (IDEC-Y2B8) is complexed to Yttrium-90 as the source of radiation. This agent is administered in lower radiation doses, thus does not require extensive preliminary dosimetry studies prior to administration of the therapeutic dose.
An additional new therapeutic agent is ONTAK (Denileukin Fiftitox). This agent joins a parti of interleuk-2 with fragments of diphtheria toxin. The interleukin-2 segment binds to CD25 on T-cell lymphoma. This brings the toxin to the location of the lymphoma and allows the toxin to kill the lymphoma cells. This antibody is highly specific for cutaneus T-cell lymphoma which carries CD25 on its surface and is very effective in controlling this disease.
In summary, modern technology has led to a number of highly specific, effective, and relatively non-toxic agents which appear to offer a new approach to the treatment of leukemia and lymphoma.