Brentuximab vedotin with nivolumab and standard chemotherapy agents produced a nearly 100% overall response rate in patents with early-stage classical Hodgkin lymphoma.
Patients with early-stage classical Hodgkin lymphoma (cHL) who were administered a frontline treatment regimen of brentuximab vedotin (Adcetris; Seagen Inc), an antibody-drug conjugate (ADC), plus a combination of the programmed cell death protein 1 (PD-1) inhibitor nivolumab (Opdivo; Bristol-Myers Squibb) and standard chemotherapy agents doxorubicin and dacarbazine (AN+AD) achieved a 98% overall response rate (ORR) at the end of treatment (EOT) during part C of a phase 2 single-arm trial (SGN35-027).
The study authors will present these data—alongside a June 17 late-breaking session to discuss a 3-year update of a 1500-patient phase 3 trial from the German Hodgkin Study Group (HD21)—at the 17th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland, from June 13 to 17.
“With teens and young adults primarily impacted by Hodgkin lymphoma, our goal is to develop curative treatments that improve survival while also reducing toxicity,” said lead study investigator Jeremy Abramson, MD, director of the Jon and Jo Ann Hagler Center for Lymphoma at Massachusetts General Hospital, in a press release.
Part C data showed that those who received the combination of brentuximab vedotin, nivolumab, and AN+AD also achieved 93% complete response (CR) rate at EOT, meeting the primary endpoint of CR at EOT as defined by the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).
The secondary endpoint was occurrence of any-grade adverse events (AEs). Among 30% of patients who experienced AEs, 65% had nausea, 47% experienced peripheral sensory neuropathy, and 44% experienced fatigue. There were no grade 5 AEs reported in the trial.
“The targeted agents of brentuximab vedotin and nivolumab have distinct mechanisms of action and demonstrated promising activity and safety in this early study,” Abramson said in the press release.”
Prior to ICML, Seagen investigators also presented data from part B of SGN35-027 at the European Hematology Association 2023 Congress in Frankfurt, Germany, which evaluated the brentuximab vedotin combination for stage 2-4 cHL. Part B data showed that 95% of patients experienced a 12-month progression free survival (PFS) rate, 93% experienced PFS at 18 months, 95% achieved ORR, and 89% experienced CR at EOT.
The 2 main types of lymphoma—a group of cancers of the lymphatic system—are Hodgkin and non-Hodgkin. In 2023, experts estimate that 8830 people in the United States will be diagnosed with Hodgkin lymphoma, characterized by CD30 (TNFRSF8) proteins on the surface of Reed-Sternberg cells.
The current standard of care for advanced stage cHL is brentuximab vedotin with adriamycin, vinblastine, and dacarbazine (AVD) chemotherapy, having demonstrated a reduced risk of death by 41% at 6-year follow-up.
But, as Abramson noted in part C, “the omission of bleomycin and vinblastine chemotherapy likely contributed to the absence of certain [AEs].”
Brentuximab vedotin with doxorubicin and different forms of chemotherapy are already indicated for various types of adult patients, which include those who have been previously treated or untreated for advanced or recurrent disease, and pediatric patients aged 2 years and older with previously untreated and high risk cHL.
“We are encouraged by the promising clinical outcomes of a [brentuximab vedotin] plus nivolumab combination with reduced chemotherapy as we seek to maximize efficacy and improve tolerability in both early- and late-stage [cHL],” said President of Research and Development and Chief Medical Officer at Seagen, Roger Dansey, in the press release.
Seagen. Seagen Announces ADCETRIS® (brentuximab vedotin) Plus Novel Immunotherapy Combination Delivers 98% Overall Response Rate and 93% Complete Response Rate in Patients with Early-Stage Classical Hodgkin Lymphoma (cHL). News Release. June 13, 2023. Accessed on June 13, 2023. https://www.businesswire.com/news/home/20230613380261/en/Seagen-Announces-ADCETRIS%C2%AE-brentuximab-vedotin-Plus-Novel-Immunotherapy-Combination-Delivers-98-Overall-Response-Rate-and-93-Complete-Response-Rate-in-Patients-with-Early-Stage-Classical-Hodgkin-Lymphoma-cHL