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ASCO: HCV Reactivation, Brain Involvement Do Not Worsen Lymphoma Survival for People with HIV

Reactivation of hepatitis C was common among HIV positive people with lymphoma, but did not appear to lead to worse outcomes or decreased survival, according to a study presented at the 50th American Society of Clinical Oncology (ASCO) meeting this week in Chicago. A related study found that having central nervous system involvement at the time of diagnosis did not decrease survival of people with AIDS-related lymphoma.

Non-Hodgkin lymphoma (NHL) is considered an AIDS-defining cancer, along with Kaposi sarcoma and cervical cancer. But lymphoma remains a concern even among HIV positive people with high CD4 T-cell counts in the era of effective combination antiviral therapy (ART). Chemotherapy to treat lymphoma can suppresses immune function, which can lead to reactivation of latent infections including hepatitis B virus (HBV); its impact on hepatitis C virus (HCV) is not well understood.

HIV/HCV Coinfection

Stefan Barta from Fox Chase Cancer Center in Philadelphia and colleagues assessed outcomes among HIV/HCV coinfected patients diagnosed with lymphoma at the Albert Einstein Cancer Center between 1997 and 2013. Out of 190 total HIV positive lymphoma patients, 28% also had hepatitis C and 9% also had hepatitis B. People with primary central nervous system (CNS) lymphoma were excluded. This analysis included 107 people with HIV alone, 50 people with HIV/HCV coinfection, and 1 person with HIV/HCV/HBV triple infection.

HIV/HCV coinfected patients were older (52 vs 44 years), were significantly more likely to have liver cirrhosis (24% vs 0%), and had a higher average Charlson comorbidity score than people with HIV alone. One-third of coinfected patients experienced hepatitis C reactivation, defined as a 3-fold or greater increase in alanine aminotransferase (ALT) -- indicating liver inflammation -- or at least a 1-log increase in HCV RNA viral load within 1 year of diagnosis. In 7% of patients reactivation persisted until 1 year after lymphoma diagnosis. No one died of liver failure.

Median overall survival was 59.7 months for HIV/HCV coinfected patients compared with 88.6 months for those with HIV alone, but the difference did not reach statistical significance (p=0.76). In a multivariate analysis adjusting for factors including demographics, CD4 count, cirrhosis, and type and stage of lymphoma, HCV coinfection was not associated with worse survival (hazard ratio [HR] 0.98). However, low CD4 count (<100 cell/mm³), advanced lymphoma stage, elevated lactate dehydrogenase level (>190 U/L), and cirrhosis were independently associated with worse overall survival. 

"While HCV reactivation is common in coinfected HIV+ patients treated for lymphoma, HCV coinfection did not portend worse overall survival in our cohort," the researchers concluded.

"Many patients do experience some reactivation of the hepatitis C virus, but in most patients it seems to be self-limited and does not affect outcomes for cancer treatment," Barta stated in a Fox Chase Cancer Center press release.

While coinfected people often take multiple medications, which increases the possibility of drug-drug interactions, and may be more susceptible to toxicities, this study suggests that the potential risks should not deter oncologists from treating them with chemotherapy, nor should they be excluded from treatment studies.  

"People should not be scared of treating patients with HIV and HCV aggressively," Barta said. "We want to assure researchers that these patients, as long as they have adequate liver function, should also be enrolled in clinical trials."

CNS Involvement

A second study by Barta and colleagues looked at outcomes among people with AIDS-related lymphoma who had CNS (brain or spinal cord) involvement at baseline or experienced CNS relapse. This analysis included 880 patients in the U.S. and Europe with newly diagnosed AIDS-related lymphoma who had available data on CNS involvement at baseline and later.

Two-thirds of patients were treated during the combination ART era. 31% received chemotherapy including rituximab. All received intrathecal administration (delivered into the space around the spinal cord) of 1 to 3 drugs to either treat or prevent CNS involvement.

At the time of diagnosis, 13% of patients had CNS involvement, which was more common among those with Burkitt's/Burkitt-like lymphoma (26%) compared to those with diffuse large B-cell lymphoma (6%).

About 5% of patients overall -- but 12% of those with initial CNS involvement -- experienced CNS relapse, at a median of 4.2 months after diagnosis. Having CNS involvement at baseline was the only factor significantly associated with CNS recurrence (hazard ratio 2.9). There was no difference in the prevalence of baseline CNS involvementor frequency of relapse between the pre- and post-ART eras.

The median survival after CNS relapse was only 1.6 months (range 0 to 86 months). However, people with initial CNS involvement did not have significantly shorter overall survival than those without (hazard ratio 0.85).

"5% of patients with AIDS-related lymphoma treated with intrathecal CNS-directed therapy experience CNS relapse; it occurs early and has a poor outcome," the researchers concluded. "We did not find a reduced frequency of CNS relapse with the use of combination ART, rituximab, or 1- vs 3-agent intrathecal CNS prophylaxis."

"Although CNS involvement at diagnosis confers a 2.9-fold higher risk for CNS relapse, it does not appear to impact overall survival, likely because of the low overall frequency of CNS relapse," they added.

"Over the last few years, people have realized that intrathecal CNS prophylaxis is probably inadequate, at least for diffuse large B-cell lymphomas, and many physicians have abandoned it," Barta said in another Fox Chase press release. "A lot of patients who relapsed probably had undetected CNS involvement at diagnosis...We want to figure out if there are better strategies to identify patients at risk."

6/4/14

References

A Sridharan, SA Curtis, JD Kaner, S Aparo, and SK Barta.Hepatitis C co-infection in HIV-positive patients treated for lymphoma. Abstract 8578.

J Joshi, N Mounier, X Xue, SK Barta, et al. CNS involvement in patients with AIDS-related lymphomas. 50th Annual Meeting of the American Society of Clinical Oncology. Chicago, May 30-June 3, 2014. Abstract 8570.

Other Sources

Fox Chase Cancer Center. Hepatitis C Reactivation Does Not Worsen Survival Outcomes for HIV+ Patients Diagnosed with Lymphoma. Press release. May 30, 2014.

Fox Chase Cancer Center. Identification of Central Nervous System Involvement at Diagnosis Does Not Affect Overall Survival for Patients with AIDS-Related Lymphomas. Press release. May 30, 2014.