This is a trial of autologous stem cell transplantation for relapsed or refractory HIV related lymphoma. First, I’d like to give you a sense of our colleagues and collaborators, including Dr Richard Little from the National Cancer Institute who is here with us this morning. This is a study that was based upon collaboration across the United States with centres from the CTN, the AMC with support from the NIH and the National Heart, Blood and Lung Association.
To date nearly 39 million people have died of AIDS or HIV related complications and given that we now have effective therapies we sometimes tend to trivialise the impact of HIV infection. Yet at this time the risk of non-Hodgkin lymphoma and Hodgkin lymphoma remains significantly elevated over that of non-HIV infected individuals. In fact, the risk of Hodgkin lymphoma hasn’t really declined with the availability of effective anti-HIV therapies. With combination anti-HIV therapies or cART that were introduced in 1996 what we did develop was an opportunity to approach this patient population differently. This combination of drugs could achieve a profound level of viral suppression, a significant improvement in T cell immunity and a decreased risk of opportunistic infections. And what that did was provide us with an opportunity to extend effective anti-lymphoma therapies to this patient population in a way that was not tenable.
Just to give you a dramatic sense, when I started in San Francisco at UCSF back in 1985 the median survival for someone diagnosed with one of these lymphomas was less than two months. So we’ve seen a dramatic evolution in what we’ve been able to offer patients.
In the late 1990s autologous transplant was extended to this patient population but still even today HIV infection remains an exclusion criterion for most autologous transplant therapeutic trials and it’s still largely limited to centres with HIV specific expertise. The purpose of this trial was to see whether or not more broadly in a nationally based trial we could extend this technology across to non-specialty centres. So this was designed as a phase II multi-centre trial using autologous transplant for patients with relapsed or refractory HIV related lymphoma. It was funded by the NHLBI, the NCI and the AIDS Malignancy Consortium and performed in collaboration between the BMTCTN and the AMC. It used one consistent preparative regimen, a combination of chemotherapy prior to transplant, the BEAM regimen, and we used a consistent management of anti-HIV therapies throughout the transplant course. The primary endpoint of this trial was overall survival and the secondary endpoints were progression free survival, lymphoma free survival, disease responses and treatment related mortality.
43 patients were enrolled on the trial; 40 underwent autologous transplant, 3 did not undergo transplant because of lymphoma progression prior to the transplant itself and they were not included in the study analysis. All patients received the modified BEAM regimen, all received blood stem cell grafts. None of the patients had any difficulty mobilising stem cells. cART therapy, anti-HIV therapy, was held during administration of the transplant preparative regimen and then resumed once nausea and vomiting related to the preparative regimen had resolved. All patients received their standard institutional supportive care throughout their course of therapy.
This is our projected twelve month survival of 86.6%, you can see the 95% confidence intervals there ranging from 70.8% to 94.2%. Progression free survival for this group of patients is projected at twelve months to be 82.3% with a 95% confidence interval from 66.3% to 91.1%. Progression at one year is estimated to be 12.5% and the mortality rate for this patient population at one year was 5%.
In order to see how this compared to non-HIV infected patients we performed a case matched control between 151 control patients identified from the CIBMTR database, that’s the Centres for International Bone Marrow Transplant Research. These patients were matched on age, performance status, disease and disease status and stage at the time of transplant. As you can see from this, the overall mortality, treatment failure, progression and treatment related mortality between groups, that’s HIV infected versus non-infected, were not statistically significantly different. When you look at overall survival in comparison between these two groups again there is no statistically significant difference between offering this form of transplant to our HIV infected patients and those matched controls.
Our conclusions are that patients with chemotherapy sensitive relapsed refractory HIV related lymphoma may be treated successfully with this modified beam regimen. The patients with treatment responsive HIV infection and HIV related lymphomas should be considered candidates for autologous transplant if they meet standard transplant criteria. Finally, we would argue that exclusion from clinical trials on the basis of HIV infection alone is no longer justified.