HIV-Positivity in Classic Hodgkin Lymphoma Shows Comparable Outcomes to Patients Without HIV

Patients with classic Hodgkin lymphoma (cHL) and human immunodeficiency virus (HIV-cHL) were found to have similar clinical outcomes compared with patients with cHL and no HIV (non–HIV-cHL). The similarities between the groups demonstrated similar overall survival (OS) prognoses, but relapse-free survival (RFS) was statically shorter in patients with HIV, according to an analysis presented during the eighth annual virtual meeting of the Society of Hematologic Oncology (SOHO).

“With this information, at the moment, it appears that prognosis of advanced-stage HIV-cHL is similar to non-HIV-cHL,” the study authors wrote in a poster presented during the meeting.

The study also revealed that having an International Prognostic Score (IPS) >3 and achieving a complete response (CR) during frontline treatment were independent prognostic factors. IPS >3 was associated with negative outcomes, whereas CRs were associated with favorable outcomes.

The analytic, observational, case-control study aimed to define outcomes for patients with HIV-cHL in response to new recommendations stating that these patients should be treated with the chemotherapy regimen of doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) along with continued combined antiretroviral therapy (CART), in the frontline setting.

In patients with HIV, the use of CART along with the presence of CD4 count >200 cells/ μL has been shown to increase the risk of developing cHL. Even without the use of antivirals, patients with HIV generally have a high risk of developing cHL. The patient population generally consists of individuals between the ages of 40 and 49 years old, which is notably higher than the median age of the general HL population. In terms of susceptibility based on patient characteristics, HIV-cHL is more common for men than women, occurring in about 6.0% versus 1.2% of these gender groups, respectively. When the disease presents, it is common for it to develop in those with extranodal disease (67% vs 32% of those without extranodal disease), B-symptoms (77% vs 43% without), and in those with stage III or IV disease (82% vs 42% with earlier-stage disease).

The study was designed to compare outcomes in patients with HIV-cHL compared to those with non–HIV-cHL in terms of OS, CR, and RFS as the primary end points. Presence of HIV in cHL was determined according to the 2016 World Health Organization criteria.

To carry out the study, 21 male patients with HIV-cHL and advanced-stage stage as well as 58 patients with non–HIV-cHL with matching disease characteristics were enrolled and assessed from August 2004 to December 2018. The average age of patients in the study was greater than 45 years for 51.7% of the patients with non–HIV-cHL versus 47.6% of the patients with HIV-cHL (P = .80). A similar proportion of patients had stage IV disease at 61.9% in the HIV-cHL group versus 69% in the non–HIV-cHL group. Notably, 66.7% of patients with HIV-cHL had a high IPS, as compared with 67.2% of those with non–HIV-cHL (P = 1.00).

The leukocyte count in the non–HIV-cHL population was 6.7 x 103 cell/μL (range, 1.1-25.4) compared with 4.6 x 103 cell/μL (range, 1.6-10.2) for a difference of P = .02. In particular, leukocytes were ≥15.0 x 103 cells/uL in 13.8% of the non–HIV-cHL population but in none of the HIV-cHL population. Results showed B-symptoms in 85.7% of patients with HIV-cHL compared with 91.4% in non–HIV-cHL (P = .43). The study authors found that patients with HIV-cHL had a lower absolute count of 340 cells/μL compared with 708 cells/μ in patients with non–HIV-cHL (P = .01). Hemoglobin levels were lower in the HIV-positive population with 52.4% having levels below 10.5 g/dL versus 36.2% in the non–HIV-cHL group.

“In our HIV-infected population, the median CD4 cell count at cHL diagnosis was 109 cells/μL, which is relatively lower than what is reported in global literature,” Juan José del Moral Díez, MD, an internal medicine fellow at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, Mexico, stated during his presentation. “A 40-month period was the median time between HIV and cHL diagnosis, and almost all of our patients were treated with antiviral therapy at the time of diagnosis.”

When outcomes were assessed based on the histopathological characteristics of patients in both groups, mixed cellularity was identified as the most common histologic subtype in 38.1% of the HIV-cHL group versus 38.9% of the non–HIV-cHL group (P = .25). In 18 patients from the HIV-cHL cohort, investigators tested for Epstein-Barr virus and all of the patients were positive. At cHL diagnosis, 90.5% of patients were receiving CART.

HIV Status and Treatment Outcomes

To evaluate outcomes, investigators used Kaplan-Meir methodology. In addition, mortality predictors were analyzed using a univariate Cox regression model. Del Moral Díez et al. assessed outcomes based on HIV positivity status in all patients in the study and then calculated responses and survival OS.

The median follow-up for response to treatment was 31 months (range, 0-215). Notably, follow-up was shorter for patients with HIV-cHL (10 months) compared with 45 months in patients with non–HIV-cHL (P = .01). Of the 56 patients in the non–HIV-cHL arm, 10.7% were not evaluable for response, and of the 18 patients in the HIV-cHL group, 11.1% were not evaluable.

Overall, the non–HIV-cHL population had a 66.1% CR rate compared with 61.1% in the HIV-cHL cohort (P = .77). Partial responses were reported in 5.4% of the non–HIV-cHL cohort and 5.6% of the HIV-cHL cohort. Stable disease or progression was observed in 17.9% of patients in the non–HIV-cHL group and in 22.2% of the HIV-cHL group. In terms of disease relapse, 30.3% of patients in the non–HIV-cHL cohort were impacted compared with 12.5% of the HIV-cHL group (P = .705).

“So far, there is no difference in the likelihood of achieving a CR in both groups,” noted del Moral Díez.

For all patients included in the analysis, the median RFS was 36.5 months. Patients with non–HIV-cHL had a median RFS of 51 months (range, 0-155) compared with 24 months (range, 0-76) among patients with HIV-cHL (P = .03).

As of the data cutoff date, the median OS was not yet reached in all study patients; however, a Cox regression model displayed during del Moral Díez’ presentation showed that patients with non–HIV-cHL had longer OS compared with those with HIV-cHL (P = .48). Another model showed that patients with IPS ≤3 had longer OS than those with an IPS >3 (P = .0056).

“RFS is statistically different in both groups and is shorter in cHL with HIV infection, but as the OS in both groups remains similar, it is possible that rescue chemotherapy is effective in such relapsed patients,” del Moral Díez said.

Prognostic Factors and Treatment Outcomes

Del Moral Díez stated during his presentation that “older age and advance clinical stage were adverse prognostic factors and an IPS of >3 was important to predict mortality. Importantly, the IPS includes both age and clinical stage as variables. We found it intriguing that mortality rates tend to be alike between cHL and HIV and cHL without HIV.”

In patients the HIV-cHL compared with non–HIV-cHL, being over the age of 45 years, and having stage IV disease adversely impacted patients (P = .02 and P = .03, respectively). The difference in how having an IPS score >3 impacted mortality was statistically significant (P = .01). Also, in terms of mortality, 28.6% of patients from the HIV-cHL cohort and 27.6% from the non–HIV-cHL cohort had died by the time of the last follow-up (P = 1.00). Overall, mortality was seen in 27.8% of the study population.

The analysis of prognostic outcome in patients with HIV-cHL versus non–HIV-cHL was conducted at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. This is the first study performed in Mexico to demonstrate seminaries in patients with advanced-stage HIV-cHL and non–HIV-cHL treated with the ABVD regimen.

_Reference:

_{Del Moral Díez JJ, Tuna-Aguila EJ, Olivas-Martinez A, et al. Outcomes of first-line treatment in patients with advanced clinical stage classic hodgkin lymphoma and human immunodeficiency virus infection. Presented at: 202 Society of Hematologic Oncology annual meeting; September 9-12, 2020. Abstract HL-323.}