TY - JOUR
T1 - Response to brentuximab vedotin versus physician's choice by CD30 expression and large cell transformation status in patients with mycosis fungoides
T2 - An ALCANZA sub-analysis
AU - Kim, Youn H.
AU - Prince, H. Miles
AU - Whittaker, Sean
AU - Horwitz, Steven M.
AU - Duvic, Madeleine
AU - Bechter, Oliver
AU - Sanches, Jose A.
AU - Stadler, Rudolf
AU - Scarisbrick, Julia
AU - Quaglino, Pietro
AU - Zinzani, Pier Luigi
AU - Wolter, Pascal
AU - Eradat, Herbert
AU - Pinter-Brown, Lauren C.
AU - Ortiz-Romero, Pablo L.
AU - Akilov, Oleg E.
AU - Trotman, Judith
AU - Taylor, Kerry
AU - Weichenthal, Michael
AU - Walewski, Jan
AU - Fisher, David
AU - McNeeley, Marise
AU - Gru, Alejandro A.
AU - Brown, Lisa
AU - Palanca-Wessels, M. Corinna
AU - Lisano, Julie
AU - Onsum, Matthew
AU - Bunn, Veronica
AU - Little, Meredith
AU - Trepicchio, William L.
AU - Dummer, Reinhard
N1 - Funding Information:
This research was co-funded by Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, and Seagen, Inc., Bothell, WA, USA, and was also funded in part through the NIH/NCI Cancer Center Support Grant [grant number P30 CA008748]. Medical writing assistance was funded by Millennium Pharmaceuticals, Inc.
Publisher Copyright:
© 2021 The Authors
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
KW - Antibody-drug conjugate
KW - Brentuximab vedotin
KW - CD30
KW - Cutaneous T-cell lymphoma
KW - Efficacy
KW - Large-cell transformation
KW - Mycosis fungoides
KW - Objective response
KW - Progression-free survival
KW - Safety
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U2 - 10.1016/j.ejca.2021.01.054
DO - 10.1016/j.ejca.2021.01.054
M3 - Article
C2 - 33794441
AN - SCOPUS:85103377885
SN - 0959-8049
VL - 148
SP - 411
EP - 421
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -