Novel Dose-Dense Multidrug Regimen Shows Promise in Relapsed/Refractory Hodgkin Lymphoma

By Megan Brooks

August 09, 2021

NEW YORK (Reuters Health) - Brentuximab vedotin can be safely combined with the second-line triple-agent chemotherapy regimen most commonly used in the U.S. for relapsed or refractory classic Hodgkin lymphoma, according to results of a single-arm phase-1/2 study.

The study showed that weekly dose-dense brentuximab vedotin combined with ifosfamide, carboplatin and etoposide (BV-ICE) is a "rapidly administered and active salvage regimen" for these patients, the study team said in The Lancet Haematology.

Although the prespecified complete-response target was not met, virtually all eligible patients ultimately proceeded with autologous hematopoietic stem-cell transplantation (HSCT).

"This study demonstrates that combining brentuximab vedotin with an intense combination chemotherapy regimen in relapsed Hodgkin lymphoma patients can produce high rates of remission, which can improve that chances of transplant success and likely cure," Dr. Ryan Lynch of the University of Washington, Seattle, told Reuters Health by email.

"Despite enrolling high-risk patients that were refractory to primary therapy, virtually all patients who were willing to proceed with a transplant after study treatment were eligible to do so. While we did not randomize patients on this study to a brentuximab vedotin-free regimen, our results appear better than the historical results which did not use brentuximab vedotin," Dr. Lynch noted.

The study included 45 patients with refractory or relapsed classic Hodgkin lymphoma. Patients received intravenous BV (1.5 mg/kg) on days one and eight with standard-dose ICE on days one, two and three for two 21-day cycles.

"Our study is unique in using a dose-dense approach to rapidly reduce the patient's tumor burden, which has hopefully improved the chance of cure," Dr. Lynch said.

After a median follow-up of 3.1 years, 32 (74%) of 43 evaluable patients had complete responses after two cycles of treatment, just shy of the 78% prespecified complete-response rate after two cycles.

"Our study is consistent with several others that have been published in recent years have consistently demonstrated the safety and efficacy of brentuximab combinations in second-line treatment of Hodgkin lymphoma prior to an autologous transplant. Our results were just under the pre-specified target, but were still very impressive, and support the use of brentuximab vedotin-based combinations in patients prior to auto transplant," Dr. Lynch told Reuters Health.

Grade-3-to-4 hematological toxicity was common, including neutropenia (73%), anemia (13%) and thrombocytopenia (80%). The most common grade-3-to-4 non-hematological toxic effects were febrile neutropenia (9%), sepsis (13%), increased alanine aminotransferase (11%), hyperglycemia (7%), pulmonary embolism (4%), and increased aspartate aminotransferase (4%).

One patient died (2%) due to multisystem organ failure that was considered treatment related. Serious adverse events occurred in 29% patients.

"Dose-dense BV-ICE might serve as an attractive salvage chemotherapy option, particularly for young, fit patients, and should be investigated in randomized trials," the researchers write.

Funding for the study was provided by Seagen, the Washington-based maker of brentuximab vedotin, and others. Dr. Lynch and some of his coauthors have financial ties to the company.

SOURCE: Lancet Hematology, online July 28, 2021.