Adcetris Plus Chemo Effective in HIV-Related Hodgkin Lymphoma

Brentuximab vedotin (Adcetris) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) was effective for patients with HIV-related stages II-IV classical Hodgkin lymphoma (cHL), according to results from the phase I/II AMC-085 study.

All 37 patients who completed therapy in the 41-patient trial achieved a complete response; at 2 years, the progression-free survival (PFS) rate reached 87% (95% CI 71-94) and the overall survival (OS) rate was 92% (95% CI 79-97).

For stage III/IV HIV-cHL specifically, 2-year rates of PFS and OS were 87% and 90%, reported Paul G. Rubinstein, MD, of the University of Illinois in Chicago, and colleagues. Median follow-up for the analysis was 29 months.

“The data suggest that the outcomes are as good or better than other regimens in HIV-cHL and at least comparable with those without HIV,” the researchers wrote in The Lancet Haematology, adding that they believe the study is “practice changing.”

Four patients had progression of disease by the last data cut-off. One treatment-related death occurred due to febrile neutropenia in cycle one, while another patient who declined treatment after cycle one and withdrew from the study died of infectious complications 1 month after withdrawal.

The most common grade ≥3 adverse events with the combination of AVD plus brentuximab vedotin, an anti-CD30 antibody-drug conjugate, were peripheral sensory neuropathy in four patients (10%), neutropenia in 18 (44%), and febrile neutropenia in five (12%).

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.

Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The study was funded by NIH and NCI and coordinated by the AIDS Malignancy Consortium, the AIDS Malignancy Consortium Lymphoma Working Group, and the Lymphoma Study Association.

Rubinstein, as well as several co-authors, reported receiving support through AIDS Malignancy Consortium grants; two co-authors reported relationships with industry.

Hoffmann and Hentrich had no disclosures.

Primary Source

The Lancet Haematology

Source Reference: Rubinstein P, et al “Brentuximab vedotin with AVD for stage II–IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial” Lancet Haematol 2023; DOI:10.1016/S2352-3026(23)00157-6.

Secondary Source

The Lancet Haematology

Source Reference: Hoffmann C, Hentrich M “Optimising treatment of HIV-associated Hodgkin lymphoma” Lancet Haematol 2023; DOI:10.1016/S2352-3206(23)00177-1.

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