A combination of Adcetris (brentuximab vedotin) and the chemotherapy gemcitabine completely eliminated the tumors in two out of three children and young adults with Hodgkin’s lymphoma in a Phase 1/2 clinical trial.
The trial, which also determined that the combination therapy was safe, included patients who had failed to respond to their first-line therapy or had an early relapse.
Trial results were published in the study, “Brentuximab vedotin with gemcitabine for pediatric and young adult patients with relapsed or refractory Hodgkin’s lymphoma (AHOD1221): a Children’s Oncology Group, multicentre single-arm, phase 1–2 trial,” in the journal The Lancet Oncology.
Hodgkin’s lymphoma patients who fail to respond to their first treatment, or who relapse less than one year after an initial response, typically have a poor prognosis. While there are other chemotherapy agents available to treat these patients, they can cause serious toxicity and may lead to secondary cancers.
Adcetris is a therapy that binds to lymphoma cells positive for the CD30 factor and delivers a toxic compound that causes cells to die. The treatment is currently approved for several lymphoma types, including those that have failed to respond to prior lines of therapy.
Studies show that Adcetris might increase lymphoma sensitivity to the chemotherapy agent gemcitabine, which has also shown promise in relapsed Hodgkin’s lymphoma alone and in combination with other agents. Gemcitabine is a chemotherapy that blocks DNA replication, resulting in cell death.
Based on this, researchers launched an open-label Phase 1/2 trial (NCT01780662) to determine the safety and effectiveness of a combination of both treatments in children and young adults with primary refractory Hodgkin’s lymphoma or early relapse.
The trial, which consisted of two parts, included patients from hospitals across the U.S. and Canada. To be eligible, a participant had to be younger than 30 and had no prior Adcetris treatment.
In Phase 1, researchers tested two Adcetris doses, given every three weeks, to determine the best and safest dose to use in combination with gemcitabine.
After deeming 1.8 mg/kg the recommended dose for additional studies, Phase 2 of the trial examined the safety and effectiveness of this dose.
Of the 42 patients treated with 1.8 mg/kg Adcetris, 31 (74%) responded to the combination therapy, including 67% who had complete responses, according to current criteria. Interestingly, most patients (88%) showing complete responses did so after the first two treatment cycles.
An additional 14% of patients achieved stable disease during the study, and one year after entering the trial, 95% of the patients remained alive.
The most common serious to life-threatening complications were low neutrophil levels, rash, elevated liver enzymes, and itchy skin. However, no patient died due to the treatment.
Investigators noted that the trial had two major limitations. First, it did not include patients previously exposed to Adcetris, who would likely show a minor response to the combination. Second, “this phase 1/2 study was not designed as a randomized trial, prohibiting any direct comparison of results after this combination with other recently published salvage regimens,” the researchers wrote.
Despite these limitations, the team concluded that “brentuximab vedotin with gemcitabine is a safe combination treatment with a tolerable toxicity profile for children and young adults with primary refractory Hodgkin’s lymphoma or early relapse.”
In an accompanying editorial, Umberto Vitolo, MD, and Annalisa Chiappella, MD, of Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino in Italy, said, “Brentuximab vedotin, in combination with chemotherapy (gemcitabine, bendamustine, or cisplatin) might represent a good alternative option that could challenge and replace more aggressive treatments.”
“However, these preliminary results should be confirmed in further randomized clinical trials,” they added.