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Clinical Trial
. 2024 Aug;51(8):1037-1049.
doi: 10.1111/1346-8138.17324. Epub 2024 Jun 14.

Phase I/II clinical trial of brentuximab vedotin for pretreated Japanese patients with CD30-positive cutaneous T-cell lymphoma

Yoji Hirai  1 , Jun Sakurai  2 , Shiho Yoshida  2 , Takashi Kikuchi  2 , Toshiharu Mitsuhashi  2 , Tomoko Miyake  1 , Taku Fujimura  3 , Riichiro Abe  4 , Hiroki Fujikawa  4 , Hikari Boki  5 , Hiraku Suga  5 , Sayaka Shibata  5 , Tomomitsu Miyagaki  5 , Takatoshi Shimauchi  6 , Eiji Kiyohara  7 , Yoshio Kawakami  1 , Shin Morizane  1
Affiliations
Clinical Trial

Phase I/II clinical trial of brentuximab vedotin for pretreated Japanese patients with CD30-positive cutaneous T-cell lymphoma

Yoji Hirai et al. J Dermatol. 2024 Aug.

Abstract

Brentuximab vedotin (BV), a conjugate of anti-CD30 antibody and monomethyl auristatin E, has emerged as a promising treatment option for refractory CD30+ mycosis fungoides (MF) and primary cutaneous anaplastic large-cell lymphoma (pcALCL). BV has been shown to be safe and effective in treating Hodgkin's lymphoma and peripheral T-cell lymphoma. This multicenter, prospective, single-arm phase I/II study evaluated the efficacy of BV in Japanese patients with CD30+ cutaneous lymphomas, namely CD30+ cutaneous T-cell lymphoma. Participants were divided into two groups: those with CD30+ MF or pcALCL (cohort 1, n = 13) and those with CD30+ lymphoproliferative disorders other than those in cohort 1 (cohort 2, n = 3). The studied population included the full analysis set (FAS), modified FAS (mFAS), and safety analysis set (SAF). These sets were identified in cohorts 1 and 1 + 2 and labeled FAS1 and FAS2, mFAS1 and mFAS2, and SAF1 and SAF2, respectively. Each treatment cycle lasted 3 weeks, and BV was continued for up to 16 cycles after the third cycle based on treatment response. The primary endpoint was the 4-month objective response rate (ORR4) determined by the Independent Review Forum (IRF). ORR4 was 69.2% for FAS1 and 62.5% for FAS2 (P < 0.0001). Secondary endpoints of ORR, assessed using the global response score (53.8% in FAS1) and modified severity-weighted assessment tool (62.5% in FAS1), using the IRF, provided results comparable to the primary findings. The incidence of ≥grade 3 adverse events (≥15%) in SAF1 was peripheral neuropathy in three patients (23%) and fever and eosinophilia in two patients (15%). In conclusion, BV showed favorable efficacy, tolerability, and safety profile in Japanese patients with relapsed or refractory CD30+ primary cutaneous T-cell lymphoma. The trial was registered with University Hospital Medical Information Network Clinical Trials Registry, Japan (protocol ID: UMIN000034205).

Keywords: anaplastic large‐cell lymphoma; brentuximab vedotin; cutaneous T‐cell lymphoma; mycosis fungoides; peripheral T‐cell lymphoma.

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Conflict of interest statement

Yoji Hirai received research grants, consultancy fees, speaker fees, and funds for staff members from Takeda Pharmaceutical Company Limited. Tomomitsu Miyagaki, Riichiro Abe, and Shin Morizane are members of Editorial Board of the Journal of Dermatology and a coauthor of this article. To minimize bias, they were excluded from all editorial decision‐making related to the acceptance of this article for publication.

Figures

FIGURE 1
FIGURE 1
Study design.
FIGURE 2
FIGURE 2
Patient disposition. PTFU, post‐treatment follow‐up.
FIGURE 3
FIGURE 3
Progression‐free survival (IRF determination, GRS). (a) FAS1. (b) FAS2. FAS, full analysis set; GRS, global response score; IRF, independent review forum.
FIGURE 4
FIGURE 4
Duration of response for skin lesions as determined by a physician at the performing institution, mSWAT. (a) FAS1 (response cases in mSWAT). (b) FAS (response cases in mSWAT). FAS, full analysis set; mSWAT, modified version of the Medical Severity Assessment Tool.
See this image and copyright information in PMC

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