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Autologous HSCT evolves as standard of care for HIV-associated lymphoma
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SAN FRANCISCO — Autologous hematopoietic stem cell transplantation conferred favorable outcomes in patients with HIV-associated non-Hodgkin’s or Hodgkin’s lymphoma, according to study results presented here.
“Autologous stem cell transplant should be considered the standard of care for HIV-infected patients with HIV-related lymphoma if they meet standard transplant criteria,” Joseph Alvarnas, MD, associate clinical professor at the City of Hope National Medical Center in Duarte, Calif., told HemOnc Today. “Patients with treatment-responsive HIV infection and lymphoma should not excluded from autologous transplant or from participation in transplant-related clinical trials based upon HIV infection alone.”
Alvarnas and colleagues evaluated data from 40 patients with treatable HIV-1 infection and chemotherapy-sensitive lymphoma who had received fewer than two salvage therapies (median age, 46.9 years). Forty percent of patients had diffuse large B-cell lymphoma, 5% had plasmablastic lymphoma, 17.5% had Burkitt’s or Burkitt’s-like lymphoma and 37.5% had Hodgkin’s lymphoma.
Most patients were in complete remission before transplant (75%), whereas 20% were in partial remission and 5% had relapsed or progressive disease.
Nine patients (22.5%) had a detectable HIV viral load and expressed a median viral load of 84 copies/mL (interquartile range [IQR], 58-234).
The median CD4 count for all patients was 250.5/mcL (IQR, 175-307).
All patients underwent a pre-transplant regimen of carmustine, etoposide, cytarabine and melphalan — or a modified BEAM regimen — followed by autologous HSCT.
The median time to neutrophil engraftment ˃500/mcL was 11 days (range, 9-32), and the median time to platelet transfusion-independent engraftment ˃20,000/mcL was 18 days (range, 9-176).
One patient died after undergoing HSCT. By 100 days post-HSCT, 36 (92.3%) of the surviving patients achieved complete remission and one patient (2.6%) achieved partial remission. The other two patients (5.1%) experienced relapsed or progressive disease.
Five patients had died 1 year after HSCT, three of whom died of recurrent or persistent disease, one of cardiac arrest and one of an invasive fungal infection. The overall rate for transplant-related mortality was 5.2% (95% CI, 0.9-15.7).
Five patients relapsed within 1 year after transplant, which equated to a 12.5% (95% CI, 4.5-24.8) 1-year cumulative incidence of relapse and progression.
After a median follow-up of 24 months post-transplant, the estimated probability of 1-year OS was 86.6% (95% CI, 70.8-94.2) and the estimated probability of 1-year PFS was 82.3% (95% CI, 66.3-91.1).
Recovery of hematological function occurred in 11 of 38 evaluable patients (28.9%) 100 days post-HSCT and in 24 of 32 evaluable patients (75%) 1 year post-HSCT.
Grade 3 toxicities occurred in 13 patients; two patients experienced grade 4 toxicities within 1 year after transplant.
Forty-two cases of infection occurred within 17 patients (42.5%). Nine of these infections were considered severe.
Alvarnas and colleagues then compared these data with 151 case-match controlled, non-HIV-infected patients with lymphoma from the Center for International Blood and Marrow Transplant Research database. Overall mortality, treatment failure, progression and transplant-related mortality were not statistically significantly different between the two cohorts. OS also was comparable between the two groups, Alvarnas said in a press briefing.
“To date, nearly 39 million people have died of AIDS- or HIV-related complications,” Alvarnas said. “Given the amount of effective therapies, we sometimes tend to trivialize the impact of HIV infection. Yet at this time, the risk of non-Hodgkin’s lymphoma and Hodgkin’s lymphoma remains significantly elevated over that of non-HIV infected individuals. In fact, the risk of Hodgkin’s lymphoma hasn’t really declined with the availability of effective anti-HIV therapies. [Results of this study show] patients with chemotherapy-sensitive relapsed/refractory HIV-related lymphoma may be treated successfully with this modified BEAM regimen.”
For more information:
Alvarnas J. Abstract #674. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2014; San Francisco.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Jeremy Slade Abramson, MD
This was a prospective clinical trial looking at the role of high-dose chemotherapy and autologous stem cell transplant in patients with HIV-associated lymphomas. HIV infection is a risk factor for developing aggressive B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma, plasmablastic lymphoma and Hodgkin’s lymphoma. One thing we know about HIV-associated lymphomas is that, in general, they present with higher risk features that, thus, produce a poorer outcome compared with their HIV-negative counterparts. A challenge in treating patients with HIV infection is that their underlying immunodeficiency related to HIV creates a higher risk for infections and other toxicities in the course of treatment.If we look at the most common HIV-associated lymphomas, DLBCL, as well as Hodgkin’s lymphoma, when these patients relapse, the standard therapy in the non-HIV population is high-dose chemotherapy with autologous stem cell support. However, high-dose chemotherapy has significant potential toxicities, including suppression of blood counts and increased risk of infections. One question that continues to be of import is whether high-dose chemotherapy can in fact be used in patients with HIV-associated lymphoma at relapse. Will it produce acceptable rates of toxicity, and will it offer similar opportunities for cure, as it does in HIV-negative patients?
In a study of 40 patients with relapsed lymphoma, patients were given second-line chemotherapy, and once they achieved remission, demonstrating chemotherapy-sensitive disease, they were then taken to high-dose chemotherapy with autologous transplant. What this study shows with a relative brief period of follow-up, is that at 1 year, 82% of patients remain progression-free from their disease, and 87% remain alive and well. The study also showed a 5% rate of treatment related mortality, which is in the range of what we expect in non-HIV affected patients treated with high-dose chemotherapy.
Thus, patients with HIV-associated lymphomas should be treated with the optimal treatment for those lymphomas, independent of the HIV infection, with good outcomes. However, additional supportive care for those patients is needed in recognition of their higher risk of infection and other toxicities.
Perspective
Back to TopBrad S. Kahl, MD
Having HIV that’s even well controlled doesn’t reduce one’s risk of developing Hodgkin’s and non-Hodgkin’s lymphoma. In many centers, HIV positivity is exclusionary from receiving stem cell transplant, which is the only potentially curative strategy for the patient population that was studied here. These data will change standard practice at centers that currently exclude HIV-positive patients, and I think the impact of that is large.
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