HIV-Associated Lymphoma: Examining Treatment Patterns and Survival in the Antiretroviral Era

As use of antiretroviral therapy has increased, the incidence of Hodgkin lymphoma (HL) among HIV-positive patients has fallen, though it has not disappeared. For HIV-positive patients with HL, treatment with chemotherapy leads to similar rates of overall survival as with HIV-negative patients. However, without appropriate chemotherapy, odds of survival drop significantly – stressing the importance of optimizing clinical management of HIV-associated HL.

“As clinicians, we should make all efforts to deliver life-extending therapy to our patients,” said Adam Olszewski, MD, assistant professor of medicine from Alpert Medical School of Brown University in Providence, Rhode Island. Dr. Olszewski presented results from an analysis of patients with HIV-associated lymphoma at the 2015 ASH Meeting on Hematologic Malignancies in Chicago. Treating HIV-associated HL requires a balance between effective cytotoxic treatment and the potential for infectious complications, he said.

Dr. Olszewski and co-investigators analyzed cases of classical HL reported to the National Cancer Data Base (NCDB) between 2004 and 2012 to examine patterns of treatment and survival in this population. They identified 2,090 HIV-positive and 41,845 HIV-negative patients in the NCDB (those with unrecorded status were assumed to be HIV-negative).

On average, HIV-positive patients were older than HIV-negative patients (median age = 43 vs. 40 years), more often male (80% vs. 53%), and black (37% vs. 11%) or Hispanic (17% vs. 8%%; p<0.00001 for all). During the study time period, the proportion of HIV-positive patients who were black increased substantially, from 31 percent to 49 percent. “As of 2012, half of HIV-positive Hodgkin lymphoma patients in the United States are black, and they are at high risk of not receiving curative chemotherapy, although it is unclear whether this is because of health-care–related factors or worse immune deficiency status,” the authors noted.

Clinically, patients with HIV were also more likely to have advanced-stage disease (stage III or IV; 66% vs. 40%) and B symptoms (64% vs. 39%).

Certain subtypes of HL were also more common among HIV-positive patients compared with HIV-negative patients (p<0.00001 for all comparisons):

  • extranodal HL (5% vs. 3%)
  • mixed cellularity subtype (22% vs. 11%)
  • lymphocyte-depleted subtype (3% vs. 1%)
  • undetermined histology (40% vs. 26%)
  • less nodular sclerosis subtype (32% vs. 57%)

The majority of HIV-positive patients received chemotherapy (81%). This proportion remained unchanged between 2004 and 2012 (p=0.29), although the authors did observe a decreasing trend of radiation therapy over time. Notably, the odds of receiving no treatment for HL was nearly twice as high for early-stage HIV-positive than HIV-negative patients (18% vs. 10%), Dr. Olszewski pointed out.

When the researchers compared receipt of chemotherapy between stage 1 or stage 2 HL patients, they found that HIV-positive patients were more often treated with chemotherapy alone (51% vs. 45%), while HIV-negative patients were more likely to be treated with a combined modality (28% vs. 41%; p<0.0001 for all). For those with advanced-stage disease, however, HIV-positive patients were less likely than HIV-negative patients to receive chemotherapy (16% vs. 9%; p<0.0001).

After adjusting for age, sex, race, stage, B symptoms, and socioeconomic status (including income and insurance status) among patients, Dr. Olszewski noted that the odds of receiving chemotherapy decreased with age, as it did with several other factors:

  • black race compared with white, OR=1.63; 95% CI 1.20-2.22)
  • uninsured status (OR=1.63; 95% CI 1.06-2.51)
  • unknown histology (compared with nodular sclerosis, OR=1.76; 95% CI 1.29-2.41)

Use of chemotherapy varied widely by hospital, but there was no difference in chemotherapy use between community and academic centers (p=0.47).

Prognosis among HIV-positive patients varied according to HL subtype, but the rates of five-year overall survival increased with receipt of standard chemotherapy across all subtypes (TABLE). For instance, overall survival at five years was not significantly different between HIV-positive and HIV-negative patients with classic nodular sclerosis or mixed cellularity subtypes – as long as patients received standard chemotherapy. “In contrast, HIV-positive patients [with unknown histology disease] had significantly worse overall survival, even with chemotherapy,” Dr. Olszewski said, “similar to overall survival of HIV-negative patients with the unfavorable lymphocyte-depleted subtype.”

Estimates of survival for all HIV-positive patients was 66.1 percent (95% CI 63.7%-68.4%) – 78.7 percent in stage I/II disease, and 59.9 percent in stage III/IV disease. Receipt of chemotherapy increased all of these rates: 73.0 percent, 83.5 percent, and 68.0 percent, respectively.

“This large contemporary analysis confirms similar survival of HIV-negative and HIV-positive Hodgkin lymphoma patients with the classical nodular sclerosis or mixed cellularity histologies, as long as they receive chemotherapy,” Dr. Olszewski and colleagues concluded.


Reference

Olszewski AJ, Castillo JJ. Management of HIV-associated Hodgkin lymphoma in the antiretroviral therapy era: analysis of the National Cancer Data Base (NCDB). Abstract #1. Presented at the ASH Meeting on Hematologic Malignancies; September 18, 2015; Chicago, IL.

TABLE. Rates of Overall Survival According to Lymphoma Histology
Histology   All patients Patients receiving chemotherapy
5-year overall survival (%) Cox model 5-year overall survival (%) Cox model
  HIV+ HIV- Hazard ratio p Value HIV+ HIV- Hazard ratio p Value
Nodular sclerosis 74.5 85.3 1.37 0.0003 80.2 87.2 1.08 0.46
Mixed cellularity 73.0 73.6 1.30 0.022 77.6 77.3 1.06 0.68
Lymphocyte-rich 74.1 81.7 1.28 0.50 71.1 84.0 1.27 0.58
Lymphocyte-depleted 57.5 57.7 1.25 0.38 69.0 64.9 1.05 0.89
Undetermined histology 55.1 71.5 1.91 <0.0001 63.5 77.0 1.56 <0.0001

 

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