The AIDS Malignancy Consortium (AMC) is a group of a dozen major medical centers, funded by the National Cancer Institute (NCI), that conduct research in the field of HIV-related cancers. The research focuses on the three most common cancers seen in people with HIV; Kaposi’s sarcoma (KS), lymphoma, and human papilloma virus (HPV)-associated anal cancer.

KS is an abnormal growth of blood vessels associated with a herpes-type virus, KS-HV or HHV-8, which most commonly appears as purple nodules on the skin. With current antiretroviral therapy (ART) the incidence of KS has declined dramatically in the past decade, but still remains a problem for many people. The AMC has several KS trials ongoing.

Lymphoma is a cancer of the lymph nodes. The most common type seen in people with HIV is non-Hodgkin’s lymphoma (NHL), but increasingly Hodgkin’s lymphoma (HL), which historically has had a higher cure rate with chemotherapy, is also occurring in people with HIV infection. With current ART, the overall incidence of lymphoma is declining, but not as much as the decline seen in KS. Fortunately, one of the most aggressive lymphomas, that of the brain, or CNS lymphoma, has had a more dramatic decline with ART. However, there still remains an ongoing need for clinical research into the treatment of HIV-associated lymphoma.

The AMC has conducted several large trials to study the best treatment for HIV-associated lymphoma. Trial 010 enrolled about 200 people and compared the standard chemotherapy regimen, CHOP, with CHOP plus rituximab, a monoclonal antibody that attacks lymphoma cells. Rituximab attacks a site on the surface of lymphocytes known as CD20. Most HIV-associated lymphomas have CD20 present on the lymphoma cell surfaces. Rituximab plus CHOP had already been shown to be better than CHOP alone in people with lymphoma who were HIV-negative. In the 010 study, better tumor control was evident in the rituximab treated group in terms of progression-free survival, and rate of death due to lymphoma, but the overall complete response (CR) rate was not significantly different in the two arms of the study. The results of this trial showed that the addition of rituximab improved the response to the chemotherapy. However, in people with very low CD4+ T-cell counts, fatal infections occurred more frequently with the addition of the rituximab, suggesting that people with less than 100 CD4 cells should also receive prophylactic antibiotics in addition to the rituximab with chemotherapy.

Following the 010 trial, the AMC conducted trial 034. This trial studied a chemotherapy regimen that is probably more potent than CHOP, but needs to be given as a four-day continuous infusion every three weeks, for two to six cycles, depending on response. The regimen is known as EPOCH. The study also asked the question if it is better to give the rituximab at the same time as the EPOCH chemotherapy, or afterwards. About 150 people enrolled in this trial. The results of the 034 trial were reported this past October at the International AIDS Malignancy Conference in Washington, DC. This trial showed very good response rates to the infusional regimen, and rituximab worked better when given at the same time as the chemotherapy rather than following the completion of the chemotherapy. In the group that received EPOCH and rituximab at the same time, there was a 65% CR rate and an estimated 80% one-year progression-free survival. In contrast, the group which received the rituximab after the EPCOH chemotherapy had 38% CR rate and an estimated 72% one-year progression-free survival. Also, in this trial, concurrent administration of rituximab was not associated with an increased risk of infectious death with the supportive care given and infection prophylaxis. These results show the dramatic improvements realized over the past decade in the treatment of HIV-associated lymphoma, when the average survival was initially measured in months, not years.

Building on the above results, the AMC has just opened its newest HIV-associated lymphoma trial 047. The title of this new study is “A Phase II Trial of Doxil, Rituximab, Cyclophosphamide, Vincristine, and Prednisone (DR-COP) in Patients with Newly-Diagnosed AIDS-Associated B-cell Non-Hodgkin’s Lymphoma (NHL).” The purpose of this trial is to determine if a chemotherapy regimen that does not require prolonged infusion of chemotherapy drugs can result in the same high response rates seen in the 034 trial. Doxil is doxorubicin (one of the most potent drugs to treat lymphoma) encapsulated in STEALTH® liposomes. Liposomes are microscopic vesicles that encapsulate active drugs, allowing them to circulate in the body longer and be more potent. Participants will receive up to six cycles of the chemotherapy, administered every 21-26 days. A total of 40 people will be enrolled in this trial.

This trial, like the earlier AMC trials, will potentially have a significant impact on the treatment of HIV-associated lymphoma. If the results of the 047 trial are found to be similar to those reported for the 034 trial, the AMC plans to continue forward with a larger randomized trial of DR-COP versus R-EPOCH in patients with newly-diagnosed AIDS-related lymphoma. In the last 10 years, the treatment and survival of people with HIV-associated lymphoma has improved dramatically and the AMC strives to continually advance this field of research.

Jeffrey T. Schouten, MD, AAHIVS is a staff physician at the University of Washington AIDS Clinical Trials Unit and community representative to the AIDS Malignancy Consortium. Contact Schouten@u.washington.edu. Contact for Alexandra Levine, MD, 047 Protocol chair: alevine@coh.org.

For more details on study 047 see http://www.cancer.gov/clinicaltrials/AMC-047. Information about AMC research sites and all ongoing AMC trials is available at the AMC website: http://pub.emmes.com/study/amc/public/about/about.htm.