Brentuximab Vedotin Plus Doxorubicin and Dacarbazine for Patients With Nonbulky Limited-Stage Classic Hodgkin Lymphoma

Results from a Phase 2 Trial

According to findings from a phase 2 trial recently published in Blood Advances, brentuximab vedotin plus doxorubicin (adriamycin) and dacarbazine combination treatment yielded durable responses and progression-free survival among patients with limited-stage classical Hodgkin lymphoma. This combination treatment additionally demonstrated an improved toxicity profile compared to the standard treatment of bleomycin, adriamycin, vinblastine, and dacarbazine, making it the superior treatment option. 

Jeremy S. Abramson, MD, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, and coauthors explained that bleomycin plus adriamycin, vinblastine, and dacarbazine—the historic standard of care for this limited-stage classical Hodgkin lymphoma—“carries risks of serious toxicities, most notably bleomycin lung injury, which can rarely be fatal, prompting consideration of non-bleomycin-containing approaches for patients with [classical Hodgkin lymphoma].” Additionally, brentuximab vedotin is approved with doxorubicin, vinblastine, and dacarbazine for stage 3 and 3 Hodgkin lymphoma, but features risks of peripheral neuropathy and neutropenic fever.

In this study, the investigators sought to evaluate brentuximab vedotin combined with doxorubicin and dacarbazine for 4 or 6 cycles, based on interim positron emission tomography response. 34 patients with non-bulky stage 1 or 2 previously untreated classical Hodgkin lymphoma were enrolled in this trial. Risk was early favorable in 53%, and was unfavorable in 47%.

Patients received brentuximab vedotin plus adriamycin and dacarbazine for 4 or 6 cycles based on interim positron emission tomography response. The overall response rate was 100% (n = 34) and the complete response rate was 97% (n = 32). The 5-year progression-free survival (PFS) was 91%. There were no significant differences in treatment outcomes based on stage or risk status. 

In terms of safety, the most common adverse events were nausea (85%), peripheral sensory neuropathy (59%), fatigue (56%), constipation (41%), alopecia (38%), and neutropenia (24%). No grade 4 neutropenia or neutropenic fever were observed. No patients required granulocyte-colony stimulating factor. Compared with the brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine regimen, the toxicity profile of brentuximab vedotin combined with doxorubicin and dacarbazine "appeared improved," with predominantly grade 1 reversible peripheral neuropathy, and no case of grade 4 neutropenia or neuropenic fever. 

Brentuximab vedotin combined with doxorubicin and dacarbazine produced a high complete response rate and durable progression-free survival, with most patients requiring 4 cycles of therapy. 

The study authors concluded that brentuximab vedotin plus doxorubicin and dacarbazine is “an appealing regimen worthy of further study in a larger trial in patients with limited-stage [classical Hodgkin lymphoma], as well as potentially in patients with low-risk advanced-stage disease, in which the overlapping toxicities of [brentuximab vedotin] and vinblastine can be significant.” 

 “[Brentuximab vedotin plus adriamycin and dacarbazine] may also serve as an appealing backbone for the addition of targeted therapies in future trials of initial therapy in [classical Hodgkin lymphoma],” they added. 

Source: 

Abramson JS, Bengtson E, Redd RA, et al. Brentuximab vedotin plus adriamycin and dacarbazine in nonbulky limited-stage Hodgkin lymphoma: results of a phase 2 trial. Blood Advances. Published online September 2, 2022. doi:10.1182/bloodadvances.2022008420