Adcetris plus chemo effective in HIV-related Hodgkin lymphoma

Rubinstein and co-authors noted that CD4+ and CD8+ T-cell counts increased in most patients, in contrast with decreases seen in cohorts treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), suggesting that the study may also have implications for people living with HIV in general. Few interventions aside from antiretroviral therapy itself have ever shown improved CD4+ T-cell counts in people living with HIV, the team explained.

Outside Experts Suggests Caution

Writing in an editorial accompanying the study, however, Christian Hoffmann, MD, PhD, of the University Hospital of Schleswig-Holstein in Kiel, Germany, and Marcus Hentrich, MD, of the University of Munich, wrote that while the data suggest that outcomes with brentuximab vedotin-AVD might be as good as those with other regimens and in people without HIV, the results should be treated with caution.

“Given one treatment-related death, four patients with progressive disease, and a 10% rate of grade 3 or worse peripheral sensory neuropathy (with three additional patients having to discontinue therapy due to toxicity), we believe it is too early to recommend brentuximab vedotin-AVD as ‘practice changing,'” Hoffmann and Hentrich said.

They also suggested that any improvement seen in OS with brentuximab vedotin-AVD compared with the standard ABVD regimen in patients with HIV-negative advanced cHL “should be weighed against the increased neurotoxicity and myelosuppression with brentuximab vedotin-AVD compared with ABVD; these adverse events should be kept into consideration especially for people living with HIV.”

However, the trial does mark another step towards optimizing treatment for HIV-associated cHL, the commentators said, adding that the results “also reemphasize the long-standing demand that people living with HIV should no longer be excluded from clinical lymphoma (and other cancer) trials.”

In explaining the rationale behind the study, Rubinstein and co-authors noted that HIV-associated cHL “remains one of the most common non-AIDS defining malignancies,” and that although outcomes for these patients have improved with the addition of antiretroviral therapy to HIV-cHL therapy, advanced-stage disease continues to have high relapse rates, warranting the need for new therapies.

Updated findings from the phase III ECHELON-1 trial showed that the 2-year PFS improvement with brentuximab vedotin plus AVD over ABVD (82.1% vs 77.2%) translated to an OS benefit at 6 years as well (93.9% vs 89.4%).

But people living with HIV were excluded from that trial, thus leading to the current single-arm trial.

The phase I/II study was conducted from 2013 to 2019 in the U.S. and France, and included 41 patients with CD30+ HIV-related cHL: seven (17%) had stage II unfavorable disease and 34 (83%) had stage III-IV disease. Participants had a median age of 48 years and 93% were male.

Patients were treated intravenously with 1.2 mg/kg of brentuximab vedotin with standard doses of AVD for six cycles on days 1 and 15 of a 28-day cycle.