Response to brentuximab vedotin versus physician's choice by CD30 expression and large cell transformation status in patients with mycosis fungoides: An ALCANZA sub-analysis

Abstract

Introduction: Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, can lead to disfiguring lesions, debilitating pruritus and frequent skin infections. This study assessed response to brentuximab vedotin in patients with MF in the phase III ALCANZA study.

Methods: Baseline CD30 levels and large-cell transformation (LCT) status were centrally reviewed in patients with previously-treated CD30-positive MF using ≥2 skin biopsies obtained at screening; eligible patients required ≥1 biopsy with ≥10% CD30 expression. Patients were categorised as CD30min < 10% (≥1 biopsy with <10% CD30 expression), or CD30min ≥ 10% (all biopsies with ≥10% CD30 expression) and baseline LCT present or absent. Efficacy analyses were the proportion of patients with objective response lasting ≥4 months (ORR4) and progression-free survival (PFS).

Results: Clinical activity with brentuximab vedotin was observed across all CD30 expression levels in patients with ≥1 biopsy showing ≥10% CD30 expression. Superior ORR4 was observed with brentuximab vedotin versus physician's choice in patients: with CD30min < 10% (40.9% versus 9.5%), with CD30min ≥ 10% (57.1% versus 10.3%), with LCT (64.7% versus 17.6%) and without LCT (38.7% versus 6.5%). Brentuximab vedotin improved median PFS versus physician's choice in patients: with CD30min < 10% (16.7 versus 2.3 months), with CD30min ≥ 10% (15.5 versus 3.9 months), with LCT (15.5 versus 2.8 months) and without LCT (16.1 versus 3.5 months). Safety profiles were generally comparable across subgroups.

Conclusion: These exploratory analyses demonstrated that brentuximab vedotin improved rates of ORR4 and PFS versus physician's choice in patients with CD30-positive MF and ≥1 biopsy showing ≥10% CD30 expression, regardless of LCT status.

Clinical trial registration: Clinicaltrials.gov, NCT01578499.

Keywords: Antibody-drug conjugate; Brentuximab vedotin; CD30; Cutaneous T-cell lymphoma; Efficacy; Large-cell transformation; Mycosis fungoides; Objective response; Progression-free survival; Safety.

Conflict of interest statement

Conflict of interest statement Y.H.K. reports advisory roles for Seagen and Takeda. H.M.P. reports advisory board for and grants or funds from Takeda. D.F. reports advisory roles for Kyowa Kirin. S.M.H. reports consulting fees from ADC Therapeutics, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, Seagen, Takeda, Verastem and Vividion Therapeutics, and research grants or funds from ADC Therapeutics, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium/Takeda, Portola Pharmaceuticals, Seagen, Trillium Therapeutics and Verastem. M.D. reports research funding from Takeda and Millennium for this study, Seagen for a physician IST, and institutional funding from Solenginex, miragene, Rhizen and Eisai. O.B. reports consulting fees from Novartis, BMS, Sanofi, Pierre, Fabre and MSD. J.A.S. reports speaker’s bureau, and consultancy/advisory roles for Takeda (Brazil). J.S. reports consulting fees from/Clinical Expert for Takeda. P.Q. reports advisory boards and speaker fee for Takeda, Kiowa, Therakos, Miragen, Helsinn-Recordati, Innate Pharma, 4SC and Actelion. P.L.Z. reports advisory roles for and honoraria from Merck, BMS, Servier, Takeda, TG Therapeutics, ADC Therapeutics, Abbvie, Incyte, Janssen, Gilead, Eusapharma, Roche, Debiopharm and Novartis. H.E. reports advisory roles for Abbvie and Genentech, honoraria from Abbvie, Genentech, Takeda and Pharmacyclics, grants or funds from Abbvie, Genentech, Pharmacyclics, Acerta, Celgene and Astrazeneca. L.C.P-B. reports advisory roles for and honoraria from Seagen. P.L.O-R. reports advisory roles for Takeda, Helsinn, 4SC, Actelion, Innate Pharma, Recordati Rare Diseases, Kyowa and miRagen, grants or funds from MEDA, and PLCG1 mutation patent. O.E.A. reports advisory roles for Trillium Therapeutics, Bioniz, Kyowa Kirin and Meivir, and research grants or funds from Actelion, Adaptive Biotechnology, Trillium Therapeutics, Pfizer and Kyowa Kirin. J.T. reports research funding from Takeda, Celgene, Roche, Beigene, Janssen and PCYC. M.W. reports honoraria from Takeda and Kyowa Kirin, and research grants or funds from Millennium. J.W. reports advisory roles for Roche, Celgene, Takeda, Janssen-Cilag, Servier, Amgen, BMS, Abbvie, Novartis and Gilead, honoraria from Roche, Celgene, Takeda, Janssen-Cilag, Servier, Amgen, Abbvie, Gilead and Novartis, grants or funds from Roche, GSK/Novartis, Takeda and Janssen-Cilag, and conference travel support from Roche. A.A.G. reports advisory roles for Seagen, Innate Pharma and StemLine Therapeutics, honoraria and grants or funds from StemLine Therapeutics, and consultancy fees from Innate Pharma and StemLine. L.B. reports employment for Zymeworks. M.C.P-W., J.L. and M.O. report employment for and ownership of stocks/shares from Seagen. V.B. reports employment for Takeda Pharmaceuticals. M.L. reports employment for and ownership of stocks/shares from Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd. W.L.T. reports employment for and ownership of stocks/shares from Takeda Pharmaceuticals. R.D. reports intermittent, project focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron and Alligator. S.W., R.S., P.W., K.T., and M.M. have no conflicts of interest to disclose.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Figures

Fig. 1.

Intra-patient, inter-patient and inter-lesional variability in baseline CD30 expression levels in patients with CD30-positive mycosis fungoides. Patients were allocated to two groups based on their biopsy with the CD30min. Patients who had at least one biopsy with <10% CD30 expression (A) were allocated to the CD30min < 10% group, and those with both/all biopsies with ≥10% CD30 expression (B) allocated to CD30min ≥ 10% group. Baseline per patient CD30 expression levels are shown in (C). Each box represents an intra-patient range of CD30 expression for individual patients. Data were plotted from highest to lowest variability in CD30 expression. Horizontal bars within each box represent median CD30 expression among all biopsies tested. The top and bottom of each box represent maximum (CD30max) and CD30min values for all biopsies from each patient. The horizontal dashed line at 10% represents the cut-off for enrollment. CD30max, maximum CD30 levels; CD30min, minimum CD30 levels.

Fig. 2.

Overall response rate lasting ≥4 months in patients with CD30-positive mycosis fungoides treated with brentuximab vedotin. Per patient objective response rate lasting ≥4 months and minimum baseline (CD30min) levels. Each box represents an intra-patient range of CD30 expression for individual patients; individual dots represent CD30 expression from individual biopsies at baseline. Data were plotted from highest to lowest variability in CD30 expression. Horizontal bars within each box represent median CD30 expression among all biopsies tested. The top and bottom of each box represent 75th and 25th percentiles; upper and lower ends of vertical dashed lines represent maximum and minimum values (for patients with two biopsies 75th and 25th percentiles overlapped maximum and minimum values). The horizontal dashed line at 10% represents the cut-off for enrollment.

Fig. 3.

Comparison of PFS with brentuximab vedotin versus physician’s choice by baseline CD30 expression level in patients with CD30-positive mycosis fungoides. CD30min, minimum CD30; CI, confidence interval; HR, hazard ratio; PFS, progression-free survival.