The Food and Drug Administration (FDA) has approved Adcetris (brentuximab vedotin) in combination with Revlimid (lenalidomide) and Rituxan (rituximab) for the treatment of adults with relapsed or refractory large B-cell lymphoma (LBCL). This includes patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma (HGBL), following two or more lines of systemic therapy and those who are ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or CAR-T-cell therapy, according to the agency.
This FDA approval was based on data from the phase 3 ECHELON-3 clinical trial which evaluated 230 patients with relapsed or refractory LBCL who were ineligible for auto-HSCT or CAR-T cell therapy. In the trial, Adcetris plus Revlimid and Rituxan (BV+R2) was compared with placebo plus Revlimid and Rituxan (Pbo+R2), resulting in a statistically significant improvement in overall survival (OS) with the investigative combination.
The median OS was 13.8 months in the BV+R2 arm and 8.5 months in the Pbo+R2 arm. Additionally, the median progression-free survival times were 4.2 months and 2.6 months, respectively, and the objective response rates were 64.3% and 41.5%.
“ECHELON-3 is one of the first randomized, placebo-controlled phase 3 studies to demonstrate an OS benefit in patients with relapsed/refractory DLBCL after two or more prior lines of systemic therapy,” said principal investigator Dr. Jeung-A Kim, College of Medicine, The Catholic University of Korea, in a news release issued in June 2024 by the drug’s manufacturer, Pfizer. “The clinically meaningful improvement in survival demonstrates the potential benefit of this Adcetris regimen in relapsed/refractory DLBCL, particularly for patients whose disease has progressed after CAR-T therapy or bispecific antibody treatment or individuals who are not able to receive these treatments.”
The most common side effects experienced by at least 20% of patients, excluding laboratory abnormalities, in the BV+R2 arm were fatigue, diarrhea, peripheral neuropathy, rash, pneumonia and COVID-19 infection, while grade 3 (severe) to 4 (life-threatening) laboratory abnormalities experienced by more than 10% of patients included decreased neutrophils, decreased lymphocytes, decreased platelets and decreased hemoglobin. The agency reported that peripheral neuropathy developed or worsened in 27% of patients, was predominantly sensory and led to Adcetris dose reduction in 6% of patients and discontinuation in 4.5%.
Data from the ECHELON-3 study were presented during the 2024 SOHO Annual Meeting.
“This triplet combination, with its promising OS benefit, has the potential to address the high unmet need of patients with relapsed/refractory DLBCL, particularly those who are not able to receive CAR-T cell therapy or bispecific antibodies or who have relapsed/refractory disease following these treatments,” Dr. Christopher A. Yasenchak, said in an oral presentation of the data.
Yasenchak is a medical oncologist and hematologist with the Willamette Valley Cancer Institute and Research Center in Oregon.
Regarding side effects, at the meeting, Yasenchak said that they “were manageable with dose modifications and consistent with the known safety profile of each individual drug.”
A type of drug known as an antibody-drug conjugate, Adcetris contains a monoclonal antibody that binds to the protein CD30 found on some lymphoma cells, and an anticancer drug, according to the National Cancer Institute.
Revlimid may help the immune system kill abnormal blood cells or cancer cells, and Rituxan binds to the protein CD20 found on B cells and some types of cancer cells, which may help the immune system kill cancer cells, The National Cancer Institute explained.
The recommended dose of Adcetris is 1.2 milligrams per kilogram to a maximum of 120 milligrams in combination with Revlimid and Rituxan administered every three weeks until disease progression or unacceptable toxicity.
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