Efficacy of Brentuximab Vedotin in Relapsed or Refractory High-CD30-Expressing Non-Hodgkin Lymphomas: Results of a Multicenter, Open-Labeled Phase II Trial

Abstract

Purpose: The treatment outcome of brentuximab vedotin (BV) has not been related with CD30 expression in previous studies enrolling patients with a wide range of CD30 expression level. Thus, this study explored the efficacy of BV in high-CD30-expressing non-Hodgkin lymphoma (NHL) patients most likely to benefit.

Materials and methods: This phase II study (Clinicaltrials.gov: NCT02280785) enrolled relapsed or refractory high-CD30-expressing NHL, with BV administered intravenously at 1.8 mg/kg every 3 weeks. The primary endpoint was > 40% disease control rate, consisting of complete response (CR), partial response (PR), or stable disease. We defined high CD30 expression as ≥ 30% tumor cells positive for CD30 by immunohistochemistry.

Results: High-CD30-expressing NHL patients (n=33) were enrolled except anaplastic large cell lymphoma. The disease control rate was 48.5% (16/33) including six CR and six PR; six patients (4CR, 2PR) maintained their response over 16 completed cycles. Response to BV and survival were not associated with CD30 expression levels. Over a median of 29.2 months of follow-up, the median progression-free and overall survival rates were 1.9 months and 6.1 months, respectively. The most common adverse events were fever (39%), neutropenia (30%), fatigue (24%), and peripheral sensory neuropathy (27%). In a post-hoc analysis for the association of multiple myeloma oncogene 1 (MUM1) on treatment outcome, MUM1- negative patients showed a higher response (55.6%, 5/9) than MUM1-positive patients (13.3%, 2/15).

Conclusion: BV performance as a single agent was acceptable in terms of disease control rates and toxicity profiles, especially MUM1-negative patients.

Keywords: Brentuximab vedotin; CD30; Multiple myeloma oncogene-1; Non-Hodgkin lymphoma.

Fig. 1.

(A) Swimmer plot for clinical course and duration of response in all patients. (B) Waterfall plot of percent change from baseline tumor size in all patients. DLBCL, diffuse large B-cell lymphoma; PMBCL, primary mediastinal B-cell lymphoma; PTCL-NOS, peripheral T-cell lymphoma not otherwise specified; AITL, angioimmunoblastic T-cell lymphoma; tMF, transformed mycosis fungoides; ENKTL, extranodal natural killer/T-cell lymphoma; BV, brentuximab vedotin.

Fig. 2.

(A) Response within each subtype. (B) Comparison of response based on percentage of CD30-positive tumor cells. (C) Progression-free survival (PFS) and overall survival (OS) for 33 patients. (D) OS between responders and nonresponders. (E) OS between relapsed and refractory patients. (F) OS based on percentage of CD30-positive tumor cells. DLBCL, diffuse large B-cell lymphoma; PMBCL, primary mediastinal B-cell lymphoma; PTCL-NOS, peripheral T-cell lymphoma not otherwise specified; ENKTL, extranodal natural killer/T-cell lymphoma; CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease.

Fig. 3.

(A) Epstein-Barr virus (EBV)–positive patients based on percentage of CD30-positive tumor cells. (B) Multiple myeloma oncogene 1 (MUM1)–negative patients based on percentage of CD30-positive tumor cells. (C) Response to brentuximab vedotin by MUM1-negative and -positive patients. (D, E) Overall survival (OS) and progression-free survival (PFS) of MUM1-negative and -positive patients. (F) OS of EBV-positive and -negative patients.

Fig. 4.

(A, B) Patients who achieved complete response (CR) with complete disappearance of fluorine-18 deoxyglucose uptake. (C) Patient with peripheral T-cell lymphoma (PTCL) showing partial response (PR) after the second cycle. His remaining target lesions disappeared after the 12th cycle (red dotted line), although new lesions appeared (yellow dotted line). (D, E) Two patients showed progressive disease (PD) after their second cycle of brentuximab vedotin. Their responses differed based on site because several lesions disappeared (red dotted line) while others progressed (yellow dotted line). MUM1, multiple myeloma oncogene 1; ENKTL, extranodal natural killer/T-cell lymphoma. DLBCL, diffuse large B-cell lymphoma.