FDA Approves New Kind of Lymphoma Treatment
On November 26 the FDA approved rituximab (Rituxan™), a monoclonal antibody, for treating certain kinds of non-Hodgkin's lymphoma. While not a cure, it appears to be an important treatment advance; also, it is the first monoclonal antibody approved to treat cancer, at least in the U.S. It has not yet been tested in persons with HIV, but such trials are now being organized. The official approval is only "for the treatment of patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin's lymphoma"; however, the drug is likely to be useful for some other lymphomas as well. (HIV-related lymphoma is usually high grade.)Rituximab works by killing B-cells, both normal and cancerous; the body can replace the normal cells after several months. B-cells produce antibodies for fighting certain infections, but no increase in infections has been found so far. Side effects of this treatment are usually much less than with conventional chemotherapy.
In one trial in 166 patients with relapsed or refractory low-grade non-Hodgkin's lymphoma (those with large tumors were excluded from this study), 6% of the volunteers had a complete response, and 42% had a partial response.1 In another trial, 46% of patients responded to rituximab treatment after they had failed conventional therapy; of the 17 responders, 14 had partial remission and three had complete remission.2
Combination use with chemotherapy seemed to work especially well in another trial.3 Forty volunteers with low-grade lymphoma were entered, 80% of them with no prior therapy. Of the 35 who completed the treatment, the response rate was 100% (60% complete response and 40% partial response). Of the other five, two did not receive treatment, and the three others had a partial response.
In addition, there is laboratory evidence that the antibody may re-sensitize tumor cells that had become resistant to the chemotherapy.4
There is concern that rituximab might be dangerous if used as initial therapy if there is a high tumor burden, because of possible toxicity from killing too many B-cells at once. To avoid this, other treatment may be used first to reduce the tumor burden. There is interest in not waiting for the chemotherapy to fail (as the officially approved indication suggests), but instead using the antibody sooner.
The approved rituximab treatment is four doses over a 22-day period--because this is what was used most in the important clinical trials. Unfortunately, the drug price to physicians for the four-course treatment is about $11,000; it is expected that insurance will pay in some cases, but be a problem in others. Rituximab was discovered by IDEC Pharmaceuticals Corp., and developed by IDEC and Genentech Inc. It is being marketed in the U.S. by Genentech.
Genentech has established a toll-free number to help with reimbursement problems, and has an Uninsured Patients Assistance Program to "provide assistance to patients whose physicians recommended treatment with Rituxan, regardless of the patients' economic or insurance status." We do not have the phone numbers or additional information at press time.
A newly formed Lymphoma Action Group began shortly before the approval. It will be working especially on increasing access to the drug, particularly for persons with HIV or others with high-grade lymphoma (who may need the most help with access, since the official indication is for low grade). To contact the group, leave a message at 415-790-5716.
References
1. Rituxan package insert, November 1997.
2. Maloney DG, Grillo-López AJ, White CA and others. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. September 15, 1997, volume 90, number 6, pages 2188-2195.
3. Czuczman M, Grillo-López AJ, White CA and others. IDEC-C2B8/CHOP chemoimmunotherapy in patients with low-grade lymphoma: clinical and BCL-2 (PCR) final results. Blood. November 15, 1996; volume 88, number 10 (supplement 1), abstract #1799.
4. Demidem A, Lam T, Alas S, Hariharan K, Hanna N, and Bonavida B. Chimeric Anti-CD20 (IDEC-C2B8) Monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biotherapy & Radiopharmaceuticals. 1997; volume 12, number 3, pages 177-186.
