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Frontline Brentuximab Vedotin Generates 76% Complete Remission Rate in DLBCL

Laura Panjwani
Published: Tuesday, Dec 22, 2015

Christopher Yasenchak, MD

Christopher Yasenchak, MD

Adding brentuximab vedotin (Adcetris) to frontline R-CHOP produced a greater than 80% response rate—including complete remissions in three-fourths of patients—as a treatment for CD30+ diffuse large B-cell lymphoma (DLBCL), according to updated interim data from an ongoing phase II clinical trial recently presented at the 2015 ASH Annual Meeting.

The trial was designed to assess antitumor activity and the safety profile of frontline brentuximab vedotin plus R-CHOP. Exploratory endpoints included CD30 expression measured by immunohistochemistry testing and the relationship between CD30 expression and response.

At ASH, data were reported from 51 DLBCL patients with a median age of 67 years. Seventy-one percent of patients in the trial had stage IV disease, 37% were considered high-risk, and 63% were considered high-intermediate risk.

Patients were randomized to receive standard R-CHOP with either 1.2 mg/kg or 1.8 mg/kg of brentuximab vedotin. However, after the first 10 patients experienced significant neurotoxicity with the 1.8-mg/kg dose, the remaining patients were all given the 1.2-mg/kg dose.

Of the 25 evaluable patients who had CD30-expressing disease, defined as 1% expression or greater, 21 patients (84%) had an objective response, including 19 patients (76%) who experienced a complete remission and 2 patients (8%) who experienced a partial remission.

The estimated progression-free survival rate for CD30-positive patients at both 12 and 15 months was 83%.

These are patients who are very much in need of novel treatment options, said study author Christopher Yasenchak, MD, an oncologist with Willamette Valley Cancer Institute and Research Center and associate chair of the Hematology Research Program with US Oncology Research, who presented the data at ASH.

“These are the worst of the worst in terms of long-term outcomes,” says Yasenchak. “Three-year progression-free survival is roughly about 55%. Many of these patients are destined to fail frontline therapy and eventually will require salvage chemotherapy, autotransplant, mini-allo transplant, and subsequently still die of their disease. RCHOP in this context, is a non-adequate treatment.”

Brentuximab vedotin also showed favorable outcomes in subsets of patients known to have a poor prognosis, according to Yasenchak.

Among eleven patients with CD30-positive activated B-cell like (ABC) DLBCL, the complete remission rate of 73% (n = 8). The estimated PFS rate for these patients at both 12 and 15 months was 80%. Among 6 patients with Epstein-Barr virus (EBV)¬–positive lymphoma, the complete remission rate was 83% (n = 5). The estimated PFS rate for these patients at 12 months was also 83%.

“The PET-negative complete response rates were higher than what we would normally expect,” said Yasenchak. “What we did not see is that patients had inferior outcomes with ABC as opposed to GBC DLBCL and several patients in the study where also EBV-positive and historically they’ve done quite poorly. EBV drives CD30 expression and CD30 is the target for brentuximab vedotin.”

The most common treatment-emergent adverse events of any grade were fatigue and peripheral sensory neuropathy (63% each), diarrhea and nausea (57% each), and neutropenia and vomiting (37% each). The most common grade III or IV adverse events were febrile neutropenia (31%), neutropenia (33%), and anemia (24%).

Based on these efficacy and safety data, the phase II trial has been amended to add a randomized cohort exploring the activity and safety of brentuximab vedotin plus RCHP (without vincristine) versus RCHOP in frontline patients with CD30-expressing high-intermediate or high-risk DLBCL. Separately, a randomized phase II trial is also ongoing evaluating rituximab and bendamustine with or without brentuximab vedotin in relapsed or refractory DLBCL.

Brentuximab vedotin is also being investigated in combination with CHP (cyclophosphamide, doxorubicin, and prednisone) as a frontline treatment for CD30-positive peripheral T-cell lymphomas. Three-year durability and survival data was recently reported at ASH 2015 from 26 mature T-cell lymphoma (MTCL) patients.

Patients who achieved at least a partial remission with combination therapy were eligible to receive continued single-agent brentuximab vedotin treatment. The median age of patients was 56 years. Nineteen patients (73%) had a subtype of MTCL called systemic anaplastic large cell lymphoma (sALCL), including 16 patients (62%) with anaplastic lymphoma kinase (ALK) negative disease, which is typically associated with a poor prognosis. Seven patients had a diagnosis of other types of MTCL. The majority of patients had advanced stage disease and were considered high risk.

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