Prognosis of HIV-Associated Hodgkin Lymphoma in the Antiretroviral Therapy Era: Analysis of the National Cancer Data Base (NCDB)

Background: The incidence of Hodgkin lymphoma (HL) among HIV-positive (HIV+) patients remains high despite the use of antiretroviral therapy. HIV+HL is characterized by a higher prevalence of the mixed cellularity (MC) subtype and by expression of Epstein-Barr virus-encoded genes. Despite poor historical outcomes, recent studies show similar overall survival (OS) among HIV+ and HIV-negative HL patients who receive standard therapy. We examined the actual proportions of HIV+HL patients receiving chemotherapy in the United States (US), and their OS, using the NCDB—a clinical oncology database capturing >70% of incident cancer cases in the US .

Methods: We analyzed classical HL cases reported to the NCDB between 2004 and 2012, with recorded HIV status. Factors associated with non-receipt of chemotherapy were studied in a mixed-effects logistic model clustered on hospital. OS was compared in Cox models adjusting for age, sex, race, stage, B symptoms and socioeconomic status, reporting adjusted hazard ratio (HR) and 95% confidence intervals (CI). CD4 counts, chemotherapy details or HL recurrences were not available in the NCDB.

Results: We identified 2,090 HIV+HL and 24,889 HIV-negative patients. HIV+ patients were on average older (median age 43 vs. 39 years in HIV-negative), more often male (80% vs. 53%), black (37% vs. 12%) or Hispanic (17% vs. 8%%, all P<.00001). The proportion of black patients increased from 31% in 2004 to 49% in 2012. HIV+HL patients had also more often advanced-stage (III/IV) disease (66% vs. 40%), B symptoms (64% vs. 41%), extranodal HL (5% vs. 3%), MC (22% vs. 12%), lymphocyte-depleted (LD, 3% vs. 1%) or undetermined histology (HL-NOS, 40% vs. 26%), and less nodular sclerosis (NS) subtype (32% vs. 57%, all P<.00001).

Early (I/II) stage HIV+HL patients were more often treated with chemotherapy alone (51% vs. 46% of HIV-negative), less frequently with combined modality (28% vs. 42%), and 18% received no treatment (vs. 9%, P<.0001). Similarly, in advanced stage they were less likely to receive chemotherapy than HIV-negative patients (84% vs. 91%, P<.0001). The proportion of all HIV+HL cases receiving any chemotherapy was 81%, unchanged between 2004 and 2012 (P=.29). Their risk of not receiving chemotherapy increased with age, and was significantly higher for patients who were black (odds ratio, OR, vs. white, 1.55, CI, 1.14-2.09), uninsured (OR, 1.65, CI, 1.08-2.51), or with HL-NOS (OR vs. NS, 1.73, CI, 1.27-2.35). It varied significantly by hospital (intraclass correlation, 9%, CI, 4-20%), but without difference between community and academic centers (P=.47).

OS at 5 years for HIV+HL patients was 66.1% overall (95% CI, 63.7-68.4%), 78.7% in stage I/II, and 59.9% in stage III/IV. Among patients who received chemotherapy, these estimates were 73.0%, 83.5% and 68.0%, respectively. OS did not improve between 2004 and 2011 (P=.18). When HIV+ and HIV-negative HL patients were compared in models adjusting for confounders (Table), OS was not significantly different in the classic NS or MC subtypes as long as patients received chemotherapy. In contrast, HIV+ HL-NOS had significantly worse OS even with chemotherapy, similar to OS of HIV-negative patients with the unfavorable LD subtype.

Conclusions: This large contemporary analysis confirms similar survival of HIV- and HIV+HL patients with the classical NS/MC histologies as long as they receive chemotherapy. HL of undetermined histologic subtype (possibly because of atypical, aggressive morphology or difficulty in obtaining an excisional nodal specimen) identifies HIV+ patients with poor prognosis despite standard therapy, who might benefit from novel, alternative approaches. As of 2012, half of HIV+HL patients in the US 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.

 

Histology		All patients					Patients receiving chemotherapy
		5-year OS (%)		Cox model			5-year OS (%)		Cox model
		HIV+	HIV-	HR	P		HIV+	HIV-	HR	P
NS		74.5	85.3	1.42	.0001		80.2	87.1	1.14	.23
MC		73.0	73.1	1.31	.026		77.6	76.8	1.14	.37
Lymphocyte-rich		74.1	81.8	1.25	.59		71.1	83.7	1.49	.38
LD		57.5	55.4	1.09	.76		69.0	62.9	0.95	.89
HL-NOS		55.1	72.0	1.85	<.0001		63.5	77.3	1.57	<.0001