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Patients with lymphoma can achieve long-term survival regardless of HIV status
Patients with the most common aggressive forms of AIDS-related non-Hodgkin’s lymphomas who receive appropriate therapy can achieve outcomes comparable to those experienced by patients who are not immunocompromised, according to results of a pooled analysis.
The improvements observed among patients with AIDS-related non-Hodgkin’s lymphoma in the contemporary era apply to all patient subgroups, researchers wrote.
Stefan K. Barta
“In our retrospective database analysis, we were able to demonstrate that outcomes for patients with AIDS-related lymphomas have significantly improved over the last 2 decades,” Stefan K. Barta, MD, of the department of medical oncology at Fox Chase Cancer Center in Philadelphia, told HemOnc Today. “This observation does not only apply to patients with low-risk disease and high CD4 counts, but also to patients with high-risk disease and low CD4 counts. With current lymphoma-directed therapy, long-term survival can be achieved for the majority of patients with newly diagnosed lymphoma irrespective of their HIV status, as long as they are being treated at specialized centers familiar with managing the complex medical issues of patients living with HIV.”
Barta and colleagues performed a pooled analysis from an existing database of patients with AIDS-related lymphomas, including diffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma or Burkitt’s-like lymphoma. The data set encompassed 19 prospective phase 2 or phase 3 clinical trials performed between 1990 and 2010 in either North America or Europe.
Researchers analyzed data from 1,546 patients to identify the association of multiple variables with complete response, PFS and OS in four different eras.
The eras were based around the introduction of antiretroviral therapy (ART) in 1996, a combination therapy that was a breakthrough in the treatment of HIV infection. Researchers labeled each era as pre-ART (1989-1995), early ART (1996-2000), recent ART (2001-2004) and contemporary ART (2005-2010).
Multivariate analysis accounted for the following variables: date of enrollment, age at enrollment, sex, histological NHL subtype, stage, lactic acid dehydrogenase levels, number of involved extranodal sites, baseline ECOG performance status, baseline CD4 count, AIDS history, type of chemotherapy, use of rituximab (Rituxan; Genentech, Biogen Idec), and concurrent use of ART with chemotherapy.
The investigators found significant shifts in patient characteristics during the course of the 2 decades; most notably in histology.
The most common lymphoma diagnosed in the pre-ART era was DLCBL (73%). In the contemporary era, the most common diagnoses were Burkitt’s or Burkitt’s-like lymphoma (55%).
The study showed improved outcomes for patients with DLCBL from one era to the next. It also showed improved outcomes for patients with Burkitt’s or Burkitt’s-like lymphoma, but only in the contemporary era.
In both univariate and multivariate analysis, Burkitt’s or Burkitt’s-like lymphoma was associated with a reduced complete response rate (OR = 0.71; 95% CI, 0.48-1.07), shortened PFS (HR = 1.36; 95% CI, 1.06-1.75) and shortened OS (HR = 1.18, 95% CI, 0.94-1.47) compared with DLBCL.
However, when comparing treatment outcomes over time, the researchers observed significant improvement for patients with DLBCL, Burkitt’s lymphoma or Burkitt’s-like lymphoma.
Among those with DLBCL, those treated in the three most recent eras demonstrated higher rates of complete response (61% vs. 47%), 2-year PFS (65% vs. 43%) and 2-year OS (57% vs. 24%) than those in the pre-ART cohort.
Among those with Burkitt’s lymphoma or Burkitt’s-like lymphoma, the rate of complete response was 56% in the pre-ART era and 59% in the three more recent eras combined; however, when researchers evaluated the contemporary ART cohort alone, the complete response rate reached 78%.
Rates of 2-year PFS (56% vs. 46%) and 2-year OS (55% vs. 37%) also were higher among patients in the three most recent cohorts compared with the pre-ART cohort.
HIV-specific factors such as an AIDS-defining illness prior to lymphoma or CD4 count less than 50 cells/mm³ were associated with lack of complete response, shorter OS and inferior PFS in certain circumstances.
In multivariate analysis, researchers determined AIDS-defining illness had an OR for complete response of 0.66 (95% CI, 0.45-0.96) and an HR for OS of 1.25 (95% CI, 1.01-1.53).
Patients with baseline CD4 counts less than 50 cells/mm³ were less likely to achieve complete response (OR = 0.42; 95% CI, 0.26-0.67) and also demonstrated shorter OS (HR = 1.78; 95% CI, 1.38-2.27). However, the 2-year OS rate for this patient population improved with time, increasing from 16% in the pre-ART era to 65% in the contemporary ART era.
Researchers observed a 2-year OS rate of 100% in the contemporary era among patients with an age-adjusted international prognostic index score of 0 (low risk). Among patients with an age-adjusted international prognostic index of 3 (high risk), complete response rates improved from 25% in the pre-ART era to 51% in the contemporary ART era. However, survival outcomes in the contemporary era remained poor, with median OS of 1.01 years and a 2-year OS rate of 49%.
“Going forward, trials need to take into consideration the unique issues of HIV-infected lymphoma patients in the modern era of targeted therapies,” Barta said. “These include, among many others, researching the complex interactions of the immune system and the tumor microenvironment, the role of oncogenic viruses in lymphomagenesis, and pharmacokinetic interactions of oral anticancer agents with antiretroviral therapy.” – by Anthony SanFilippo
For more information:
Stefan K. Barta, MD can be reached at Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111; email: stefan.barta@fccc.edu
Disclosure: The researchers report no relevant financial disclosures.