Conference Coverage: Brentuximab Vedotin Plus A-AVD Leads to High Response Rates in HL, But Safety Concerns Exist

CHICAGO—Patients with limited Hodgkin lymphoma are typically treated with ABVD (adriamycin/bleomycin/vinblastine/dacarbazine) plus radiation, though the regimen confers a greater risk of bleomycin-related lung injury and radiation toxicity.

In a recent study presented at the 2015 ASCO Annual Meeting by Jeremy S. Abramson, MD, adding the anti-CD30 antibody drug conjugate brentuximab vedotin (BV) to AVD (adriamycin/vinblastine/dacarbazine) led to high response rates and improved overall (OS) and progression-free survival (PFS) in patients with non-bulky stage 1 and 2 Hodgkin lymphoma.

Dr. Abramson, from the Massachusetts General Hospital in Boston, and colleagues analyzed the response and survival rates in 34 patients in this multicenter, phase II study. Patients had a median age of 36 years (range, 20-75 years). Sixty-two percent of patients had favorable risk and 38 percent had unfavorable risk.

According to study protocol, patients received a lead-in cycle of BV monotherapy (1.2 m/kg on days 1 and 15) followed by a positron emission tomography (PET) scan. Patients then received four to six cycles of A-AVD, depending on the results from the interim PET-computed tomography scan.

The study’s primary endpoint was complete response rate (CRR).

After the BV monotherapy lead-in, 18 patients (53%) reached complete remission (CR). Later, after two cycles of A-AVD, that number increased to 33 patients (97%). However, two patients were removed from the study due to toxicity.

At the end of treatment, 30 patients (88%) reached CR; again, though, two of these patients had progressive disease and two were removed for toxicity.

Overall, eight patients had positive PET scans at the end of treatment. Six of these patients were viewed as “reactive” according to the investigators. On a brief follow-up scan, however, all six patients were in confirmed CR with no intervening therapy, confirming the investigators’ suspicions that the scans produced false-positive results.

At a median follow-up of 14 months, PFS and OS were 90 percent and 97 percent, respectively.

In terms of safety, the most common treatment-related adverse events were peripheral neuropathy (74%), fatigue (71%), neutropenia (68%), anemia (56%), constipation (56%), diarrhea (35%), abdominal pain (32%), and nausea (24%). Grade 3 and 4 toxicities occurred in 26 of the patients, and included neutropenia (56%), febrile neutropenia (29%), and peripheral neuropathy (24%).

One older patient died of neutropenic sepsis in the first A-AVD cycle, while another patient was removed from the study after experiencing grade 2 hypersensitivity, despite premedication. Also, reductions in BV were required in 38 percent of patients – mostly due to peripheral neuropathy.

So, while the four cycles of A-AVD produced a high CRR, the treatment was associated with more toxicity than AVD alone. Dr. Abramson added that false-positive results from PET scans were common on end-of-treatment imaging and warrant further attention.

Source: Abramson JS, Arnason JE, LaCasce AS, et al. Brentuximab vedotin plus AVD for non-bulky limited stage Hodgkin lymphoma: A phase II trial. Abstract #8505. Presented at the 2015 American Society of Clinical Oncology Annual Meeting, Chicago, Illinois, June 1, 2015.