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

Youn H Kim; H Miles Prince; Sean Whittaker; Steven M Horwitz; Madeleine Duvic; Oliver Bechter; Jose A Sanches; Rudolf Stadler; Julia Scarisbrick; Pietro Quaglino; Pier Luigi Zinzani; Pascal Wolter; Herbert Eradat; Lauren C Pinter-Brown; Pablo L Ortiz-Romero; Oleg E Akilov; Judith Trotman; Kerry Taylor; Michael Weichenthal; Jan Walewski; David Fisher; Marise McNeeley; Alejandro A Gru; Lisa Brown; M Corinna Palanca-Wessels; Julie Lisano; Matthew Onsum; Veronica Bunn; Meredith Little; William L Trepicchio; Reinhard Dummer

doi:10.1016/j.ejca.2021.01.054

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

Eur J Cancer. 2021 May:148:411-421. doi: 10.1016/j.ejca.2021.01.054. Epub 2021 Mar 29.

Authors

Youn H Kim¹, H Miles Prince², Sean Whittaker³, Steven M Horwitz⁴, Madeleine Duvic⁵, Oliver Bechter⁶, Jose A Sanches⁷, Rudolf Stadler⁸, Julia Scarisbrick⁹, Pietro Quaglino¹⁰, Pier Luigi Zinzani¹¹, Pascal Wolter¹², Herbert Eradat¹³, Lauren C Pinter-Brown¹⁴, Pablo L Ortiz-Romero¹⁵, Oleg E Akilov¹⁶, Judith Trotman¹⁷, Kerry Taylor¹⁸, Michael Weichenthal¹⁹, Jan Walewski²⁰, David Fisher²¹, Marise McNeeley²², Alejandro A Gru²³, Lisa Brown²⁴, M Corinna Palanca-Wessels²⁵, Julie Lisano²⁶, Matthew Onsum²⁷, Veronica Bunn²⁸, Meredith Little²⁹, William L Trepicchio³⁰, Reinhard Dummer³¹

Affiliations

¹ Dermatology and Medicine, Stanford University School of Medicine and Cancer Institute, 780 Welch Road, CJ220D, 94305, Stanford, CA, USA. Electronic address: [email protected].
² Department of Haematology, University of Melbourne, 140 Clarendon Street, 3002, East Melbourne, Australia. Electronic address: [email protected].
³ St Johns Institute of Dermatology, Guys and St Thomas NHS Foundation Trust, St Thomas Street, SE1 7EL, London, UK. Electronic address: [email protected].
⁴ Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, 10065, New York, NY, USA. Electronic address: [email protected].
⁵ Department of Dermatology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1452, 77030, Houston, TX, USA. Electronic address: [email protected].
⁶ Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. Electronic address: [email protected].
⁷ Department of Dermatology, University of São Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar 255, S. 3068, 05403-000, São Paulo, Brazil. Electronic address: [email protected].
⁸ University Clinic for Dermatology, Johannes Wesling Medical Centre, Hans-Nolte-Str. 1, D-32429, Minden, Germany. Electronic address: [email protected].
⁹ Department of Dermatology, Cutaneous Lymphoma Service, University Hospital Birmingham, Mindelsohn Way, B15 2TH, Birmingham, UK. Electronic address: [email protected].
¹⁰ Department of Medical Sciences, Dermatologic Clinic, University of Turin, Via Cherasco 23, 10126, Turin, Italy. Electronic address: [email protected].
¹¹ Institute of Hematology 'Seràgnoli', University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. Electronic address: [email protected].
¹² Department of Internal Medicine/Medical Oncology, Klinik St. Josef, St Vith, Klosterstrasse 9, 4780, St Vith, Belgium. Electronic address: [email protected].
¹³ Department of Hematology-Oncology, David Geffen School of Medicine at UCLA, 2020 Santa Monica Blvd Suite 600, 90404, Los Angeles, CA, USA. Electronic address: [email protected].
¹⁴ Internal Medicine, Division of Hematology-Oncology, Chao Family Comprehensive Cancer Center, University of California, 101 The City Drive, 92868, Irvine, CA, USA. Electronic address: [email protected].
¹⁵ Department of Dermatology, Hospital 12 de Octubre. Institute I+12. Medical School. University Complutense, Av Córdoba s/n, 28041, Madrid, Spain. Electronic address: [email protected].
¹⁶ Department of Dermatology, University of Pittsburgh, 200 Lothrop Street, 15213, Pittsburgh, PA, USA. Electronic address: [email protected].
¹⁷ Department of Hematology, Concord Repatriation General Hospital, University of Sydney, Hospital Road, 2139, Concord, Sydney, Australia. Electronic address: [email protected].
¹⁸ Department of Hematology, ICON Cancer Care, 293 Vulture Street, 4101, South Brisbane, Australia. Electronic address: [email protected].
¹⁹ Department of Dermatology, University Hospital of Schleswig-Holstein, Arnold Heller Str.3, 24105, Kiel, Germany. Electronic address: [email protected].
²⁰ Department of Lymphoid Malignancies, Maria Sklodowska-Curie National Research Institute of Oncology, 5 W. K. Roentgen, 02-781, Warsaw, Poland. Electronic address: [email protected].
²¹ Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, 02215, Boston, MA, USA. Electronic address: [email protected].
²² Department of Anatomic Pathology for Clinical Trials, Quest Diagnostics, 1 Malcolm Avenue, 07608, Teterboro, NJ, USA. Electronic address: [email protected].
²³ Department of Pathology, University of Virginia, School of Medicine, 2730 Hunt Country Ln, 22901, Charlottesville, VA, USA. Electronic address: [email protected].
²⁴ Seagen Inc, 21823 30th Drive Southeast, 98021, Bothell, WA, USA. Electronic address: [email protected].
²⁵ Seagen Inc, 21823 30th Drive Southeast, 98021, Bothell, WA, USA. Electronic address: [email protected].
²⁶ Seagen Inc, 21823 30th Drive Southeast, 98021, Bothell, WA, USA. Electronic address: [email protected].
²⁷ Seagen Inc, 21823 30th Drive Southeast, 98021, Bothell, WA, USA. Electronic address: [email protected].
²⁸ Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, 40 Landsdowne Street, 02139, Cambridge, MA, USA. Electronic address: [email protected].
²⁹ Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, 40 Landsdowne Street, 02139, Cambridge, MA, USA. Electronic address: [email protected].
³⁰ Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, 40 Landsdowne Street, 02139, Cambridge, MA, USA. Electronic address: [email protected].
³¹ Department of Dermatology, Skin Cancer Center, University Hospital Zürich, Gloriastrasse 31, 8091, Zürich, Switzerland. Electronic address: [email protected].

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 CD30_min < 10% (≥1 biopsy with <10% CD30 expression), or CD30_min ≥ 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 CD30_min < 10% (40.9% versus 9.5%), with CD30_min ≥ 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 CD30_min < 10% (16.7 versus 2.3 months), with CD30_min ≥ 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.

Publication types

Clinical Trial, Phase III
Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological / therapeutic use*
Brentuximab Vedotin / therapeutic use*
Choice Behavior*
Decision Support Techniques*
Female
Follow-Up Studies
Humans
International Agencies
Ki-1 Antigen / metabolism*
Male
Middle Aged
Mycosis Fungoides / drug therapy*
Mycosis Fungoides / metabolism
Mycosis Fungoides / pathology
Physicians / psychology
Physicians / statistics & numerical data*
Prognosis
Retrospective Studies
Survival Rate
Young Adult

Substances

Antineoplastic Agents, Immunological
Ki-1 Antigen
Brentuximab Vedotin

Associated data

ClinicalTrials.gov/NCT01578499

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States