Autologous Stem Cell Transplantation Offers Safe, Effective Option for Patients With HIV-Associated Lymphoma
A phase II, multicenter trial published by Alvarnas et al in Blood challenges the generally held belief that individuals with human immunodeficiency virus (HIV) and aggressive lymphoma are not candidates for standard treatment.
According to the researchers, people with HIV-associated lymphoma who receive autologous stem cell transplant (ASCT) have similar survival rates and are no more at risk of serious complications compared to those without HIV receiving this therapy. People living with HIV—even those whose infection is well controlled with modern combination antiretroviral therapy—remain at significant risk of cancer. The risk of non-Hodgkin lymphoma alone is up to 25-fold greater for people with HIV than for those without the infection, and malignancies have quickly become a leading cause of death as people with HIV live longer.
ASCT has become the standard of care for treating relapsed and treatment-resistant Hodgkin and non-Hodgkin lymphoma. However, its use in HIV-infected patients is largely limited to centers with HIV-specific expertise.
Clinicians have historically been hesitant to treat HIV patients with stem cell transplant due to concerns that their immune systems would not effectively recover after intensive chemotherapy or that the procedure would cause excessive toxicities or infections post-transplant. However, in this phase II clinical trial, designed to prospectively evaluate the safety and effectiveness of ASCT for patients with HIV-related lymphoma, researchers discovered that this population had no greater likelihood of developing these complications compared to those without the virus.
“Overall survival for patients with HIV infection after transplant is comparable to that seen in people who were not HIV-infected,” said lead author Joseph Alvarnas, MD, Associate Clinical Professor in the Department of Hematology and Director of Value-Based Analytics at the City of Hope National Medical Center.
The data also showed that transplant-related toxicities in these patients are comparable to those observed in patients without HIV.
“These findings are remarkably important for a group of patients who, up until now, have been inconsistently treated,” Dr. Alvarnas said. “Transplantation allows clinicians to treat the cancer most effectively by using more intense doses of chemotherapy than can typically be given, while avoiding fears of wiping out the bone marrow. Based on our data, autologous stem cell transplant should be considered the standard of care for patients with HIV-related lymphomas for the same indications and under the same circumstances that we would use it in patients without HIV infection.”
Study Findings
In this study, prior to giving intensive BEAM chemotherapy (carmustine [BiCNU], etoposide, cytarabine, and melphalan), researchers collected stem cells from each patient’s blood. These stem cells were frozen and then later administered to the patient intravenously to rescue the patient after therapy.
A total of 43 patients with treatable HIV infection who had chemotherapy-sensitive relapsed/treatment-resistant non-Hodgkin or Hodgkin lymphoma were enrolled in this trial between April 2010 and March 2013; 40 received ASCT at 16 centers. Three patients did not receive a transplant due to disease progression.
Patients underwent frequent lab testing and received supportive care post-ASCT based on institutional standards. Disease status was assessed before ASCT, at day 100, and at 1 year post-transplantation. Researchers then compared patients in the trial to 151 similar patients who did not have HIV but received the same treatment for lymphoma using data reported to the Center for International Blood & Marrow Transplant Research (CIBMTR).
After a median follow-up of 25 months, overall survival at 1 and 2 years post-transplant was 87.3% and 82%, respectively. This was comparable to those without HIV, whose overall survival at 1 year was 87.7%. The probability of 2-year progression-free survival among those with HIV was 79.8%.
The rate of 1-year transplant-related death was 5.2%, resulting from recurrence/persistence of the lymphoma, fungal infection, and cardiac arrest, which was comparable to the non-HIV patients. Median time to white blood cell and platelet recovery was 11 and 18 days, respectively. Within 1 year of ASCT, 15 patients developed severe toxicities and 17 had at least one infection.
Patients with HIV infection remained in good control over their disease post-transplant. Most patients (82%) still had undetectable levels of the virus after 1 year.
“When you look at people’s recovery—recovery of their T cells and CD4-positive cells and suppression of viral load—we don’t see people losing control of HIV infection, nor do they have evidence of additional immunologic deficits following transplant. I think that’s very reassuring,” said Dr. Alvarnas.
Algorithm for HIV Treatment
Historically, it has also been a challenge to manage antiretroviral therapy in patients undergoing chemotherapy due to potential drug-drug interactions. According to the author, this study is unique in that researchers used a consistent algorithm for treating HIV infection, which involved avoiding certain drugs and having a planned interruption in antiretroviral therapy that took place from initiation of chemotherapy until completion of the preparative regimen or following recovery from transplant-related gastrointestinal toxicities (roughly 1 week).
“This is an important study because we need to better understand the long-term effects of HIV infection to ensure that patients are equitably treated in a way that respects their medical regimens and the biology of their HIV infection,” he said.
Clinical trial research is also ongoing to evaluate the safety of allogeneic hematopoietic cell transplantation for HIV-infected patients with blood cancers.
The trial (BMT CTN 0803/AMC 071) was funded by the Blood and Marrow Transplant Clinical Trials Network and the AIDS Malignancy Consortium working in collaboration with the National Heart, Lung, and Blood Institute and the National Cancer Institute.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
