Gay Men's Health Crisis: Treatment Issues, Volume 7 no. 5 - May, 1993
Gabriel Torres, M.D. and David Straus, M.D.

Pluda and colleagues form the National Cancer Institute report an increased incidence of NHL among AIDS patients treated with zidovudine (AZT) for over two years. They speculate the increase is related to prolonged survival despite profound immunosuppression.[2] The expanded use of combination antiretroviral therapies and prophylaxis for multiple opportunistic infections are expected to increase survival and, therefore, may lead to an increase number of cases of lymphoma in people with AIDS in the next several years, making the search for new treatments more critical. HD has also been reported with increased incidence in HIV-infected people, yet is associated with a better outcome than NHL.[3, 4]

The prognosis for a PWA with NHL is poor; median survival is only six months in most cases.[5, 6] Death is directly related to the lymphoma in approximately 50 percent of patients and to infections, probably aggravated by side effects of chemotherapy, in the rest.[7] In some cases, however, prolonged, complete remissions with disease- free survival for more than one year have been attained with combination chemotherapy. One research team reports that a CD4 count greater than 100 predicts long term survival for patients with NHL.[8] Other predictors include no other concurrent AIDS-defining illnesses and absence of disease outside of the lymphatic system. In patients with good prognostic factors who are treated with AZT and prophylaxis, low-dose chemotherapy achieves a median survival of five to six months.[9] In those with poor prognostic factors, chemotherapy does not affect the rate of complete remission and survival is 3.5 months.[10]

Monoclonal Antibodies

A new experimental approach to treating HL and NHL is monoclonal antibody therapy. Antibodies are proteins produced by immune cells to respond to infection or cancer. Monoclonal antibodies are produced in laboratories using clones of a single immune cell. Monoclonal antibody technology can produce large quantities of one antibody. Monoclonal antibodies have two properties which lead scientists to believe they may be used therapeutically. In some cases, they are directly cytotoxic; monoclonal antibodies, on their own, may destroy unwanted cells. In other cases, the monoclonal antibodies have no destructive effects themselves but can carry toxins or radioactive particles directly to target cells or tissues.

Lymphoma patients considering monoclonal antibody therapy must have a biopsy of their tumor to ensure it reacts to the monoclonal antibody under investigation. A short initial hospitalization is usually required to observe the effects of the monoclonal antibody therapy. In addition, a catheter may be required to administer safely the experimental agents and to obtain frequent blood samples. Patients must be strong enough to live at home and take care of most of their personal needs.

Three monoclonal antibodies are being studied at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, two for the treatment of NHL and one for HD. For NHL patients, OK B7, a monoclonal antibody attached to radioactive iodine, is under investigation. A phase I trial of the OK B7 monoclonal antibody among eighteen patients with relapsed NHL showed that the therapy was nontoxic and well-tolerated at six dose levels ranging from 0.1 to 40mg.[11] The investigation was able to show that the tumor cells which expressed the OK B7 antigen had uptake of the radioactive monoclonal antibody compared with tumor cells which did not express the antigen. No lymphoma regression could be attributed to the OK B7 infusions; altogether three patients had complete remission for eleven to twelve months; these three had the highest percentage of uptake of OK B7 per dose in their mode. Little is known about the side effects of radioactive monoclonal antibodies; some potential side effects may include allergic reactions, fevers, chills, low blood pressure, and liver and kidney problems. Possible side effects of radiation include low blood counts, infections, bleeding, and the development of other cancers.

For NHL patients ineligible for the OK B7 protocol, monoclonal antibody anti-B4 is under investigation. Anti-B4 is linked to ricin, a potent immunotoxin derived from the castor bean. Anti-B4 blocked ricin will attach to most lymphoma cells but not normal tissue. Ricin is chemically altered so that it will only slightly affect normal tissues. Preclinical studies of anti-B4 blocked ricin in monkeys demonstrated that its main toxicity is elevation of liver enzymes. A Phase I trial of the drug in 25 non-HIV infected patients with NHL was performed at the Dana Farber Cancer Institute.[12] The drug was given as a single one-hour bolus infusion for five days at doses ranging from 1mg/1kg/d to 60mg/1kg/d. The study confirmed that the main toxicity is elevated liver function tests. Two patients had a drop in platelet counts. One patient had a complete response, two had partial responses, and eight had mixed or transient responses. Other side effects of the monoclonal antibody include allergic reactions and weight gain due to fluid retention. One advantage seems to be that it does not cause significant neutropenia.

A monoclonal antibody recognizing R24, an antigen found in HD, is also under investigation. The R24 antibody also recognizes T cell lymphoma cells, though these tumors are quite rare. For more information on the monoclonal antibody studies, call Dr. David Straus at Memorial Sloan Kettering Cancer Center at 212/639- 8365.

Chemotherapy for Hodgkin's Disease

An Italian research team reports the results of MOPP (a combination chemotherapy regimen including methotrexate, oncovin, prednisone, and procarbazine) with or without radiation therapy in a large group of HIV-infected persons with HD. Complete remissions occurred in 50 percent of patients and partial remissions in 45 percent.[13] Average survival was sixteen months; however, 61 percent of patients developed opportunistic infections during the follow-up period. None of the patients in this trial received AZT. In a related study, the researchers alternated MOPP with ABVD (a combination chemotherapy regimen including adriamycin, bleomycin, vinblastine, and dacarbazine): The alternating regimen was better tolerated than MOPP alone. In a smaller group of patients, chemotherapy was given with AZT. Only one opportunistic infection occurred, although the rates of complete and partial remissions were similar.

One concern regarding use of chemotherapy in HIV-positive persons with HD has been the occasional transformation of HD into high- grade NHL, which has been reported in one case.[14]

Conclusion

Although treatment options for AIDS-related lymphomas are limited, new strategies with combination chemotherapy or monoclonal antibodies are being developed which may improve survival and extend remissions. The primary prevention of lymphomas, probably through inhibition of Epstein Barr Virus replication or other oncogenic agents, still needs to be pursued since cases of lymphoma are expected to increase as people with AIDS live longer in an immunosuppressed state.

1. Hessol NA, Katz MH, et al. Annals of Internal Medicine. 1992; 117:309-11.

2. Pluda JM, Yarchoan R, et al. Annals of Internal Medicine. 1990; 113:276-282.

3. Hessol NA, Katz MH, et al. Annals of Internal Medicine. 1992; 117:309-11.

4. Rothmann S, Tourani JM, Andrieu JM. New England Journal of Medicine. 1990;323:275-6.

5. Ziegler JL, Beckstead JA, et al. New England Journal of Medicine. 1984; 311:565-570.

6. Lowenthal DA, Straus DJ, et al. Cancer. 1988; 61:2325-2337.

7. Gill PS, Levine AM, et al. Journal of Clinical Oncology. 1987; 5:1322-1328.

8. Kaplan LD, Abrams DI. JAMA. 1989; 261:719-24.

9. Levine AM,Wenz JC, et al. JAMA. 1991; 266:84-88.

10. Tirelli U, Errante D, Oksenhendler E. JAMA. 1992; 267:509.

11. Scheinberg DA, Straus DJ, Yeh SD. Journal of Clinical Oncology.1990; 8:792-803.

12. Grossband ML, Freed AS, Ritz J. Blood. 1992:576-585.

13. Vaccher E, Tirelli U, Chieppa F. Abstract Mo0059. Presented at VIII International Conference on AIDS, Amsterdam, 1992.

14. Montalban C., Rodriguez JL, Aguado M. Blood.1990; Suppl 1:76.

Copyright (c) 1993 - GMHC Treatment Issues. Distributed by AEGIS, your online gateway to a world of people, knowledge, and resources. http://www.aegis.com

930501
GM070503

Copyright © 1993 - Treatment Issues. Reproduced with permission. Treatment Issues is published twelve times yearly by GMHC, Inc. All rights reserved. Noncommercial reproduction is encouraged. Subscription lists are kept confidential. GMHC Treatment Issues, The Tisch Building, 119 West 24th Street, New York, NY 10011  fredg@gmhc.org  http://www.gmhc.org

AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2003. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2003. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .