For patients with Hodgkin lymphoma and HIV infection, the response to chemotherapy can be expected to be about the same as for those without HIV infection. That was the conclusion of two studies published simultaneously, available online ahead of print in the Journal of Clinical Oncology. One was the largest prospective study to address the question (doi: 10.1200/JCO.2012.41.8137); and the other, although retrospective, had a median follow-up of 60 months (doi: 10.1200/JCO.2011.41.4193).
“I feel that the preponderance of data strongly suggests that patients with HIV-associated Hodgkin lymphoma should be treated in an identical manner as for HIV-negative patients,” the lead author of the prospective study, Marcus Hentrich, MD, Associate Professor in the Department of Hematology, Oncology, and Palliative Care at the University of Munich, said in an interview.
He said that although the results of these and previously published studies show that HIV patients tend to have worse prognostic markers and more extensive disease at the time of diagnosis compared with those without HIV, the benefit of established regimens is similar. Neither study found a significant negative impact of HIV on any key endpoint, including overall survival.
The Retrospective Study
The retrospective study evaluated 93 HIV patients within a series of 224 consecutively treated newly diagnosed Hodgkin patients, and neither the difference in five-year event-free survival rates (59% in those with HIV vs. 66% in those without HIV) nor the difference in five-year overall survival rates (81% vs. 88%, respectively) was statistically significant.
The regimens evaluated are the ones most widely used in current practice: In the retrospective study, all received ABVD (doxorubicin, bleomycin, vincristine, and dacarbazine). In the prospective study, 23 of the 108 patients had early favorable disease and received ABVD followed by radiation.
Of the remaining patients, 14 had early unfavorable Hodgkin and received either four cycles of ABVD plus radiation or four cycles of BEACOPP baseline (bleomycin, etoposide, cyclophosphamide, vincristine, procarbazine, and prednisone). The 71 patients with advanced-stage Hodgkin lymphoma received six to eight cycles of BEACOPP baseline.
The Prospective Study
In the prospective study, the overall survival rate at two years for the entire study population was 90.7 percent. The progression-free survival rate at two years was 91.7 percent. The complete remission rates were in line with what has reported in the past for Hodgkin patients without lymphoma, approaching 100 percent in the early groups and 86 percent in patients with advanced disease, he said.
The ability of HIV patients with Hodgkin lymphoma to derive the same benefits from chemotherapy and radiation as those without HIV is credited to restoration of immune function by highly active antiretroviral therapy (HAART) regimens. However, in the prospective study it was recommended that BEACOPP be replaced by ABVD in patients with advanced HIV-infection (defined as having two or three of the following risk factors: CD4 lymphocyte counts less than 50/μl; prior AIDS-defining opportunistic infection; and a performance status greater than 2).
Importance of Immune Function
Asked about importance of immune function, the lead author of the retrospective study, Silvia Montoto, MD, of the Centre for Haemato-Oncology at Barts Cancer Institute of Queen Mary University in London, said that it is unusual for patients with HIV to have very low CD4 counts at diagnosis of Hodgkin lymphoma, but if that is the case it should not change the management in terms of the chemotherapy regimen. However, the very low CD4 counts may change management “in terms of prophylaxis of opportunistic infections,” he said.
Asked for his opinion for this article, Lawrence D. Kaplan, MD, Director of the Adult Lymphoma Program at the University of California, San Francisco, said that relative to the dismal prognosis for HIV-infected patients with Hodgkin lymphoma before the era of HAART (typically overall survival rates of less than 20 percent), the new data are “remarkable.” Kaplan, who wrote an editorial that accompanied publication of the two studies (doi/10.1200/JCO.2012.44.8373), concurred with both investigators that HIV infection should not change the treatment approach.
In the study by Montoto et al, the rates of toxicity were somewhat higher in those with HIV than in those without, but did not appear to adversely affect outcomes. The toxicities overall in HIV patients are manageable, she said, and both Hentrich and Kaplan agreed. Moreover, all three agreed that HIV patients with Hodgkin lymphoma should now be considered eligible for enrollment in trials with investigational agents.
The possible exception is escalated BEACOPP, a dose-intensive regimen that was not investigated in the prospective study. However, Hentrich noted, “the role of the escalated BEACOPP regimen for advanced Hodgkin is controversial even in the HIV-negative population.”
Overall, the message from these two most recent studies is that HIV infection should not be an obstacle for selecting the therapy for Hodgkin lymphoma with the greatest likelihood of efficacy. Although both Hentrich and Montoto cautioned that clinicians should consider any risk of drug interactions between antiretroviral and chemotherapy agents, the important news is that HIV patients with Hodgkin lymphoma have a prognosis that rivals an HIV-negative population.