Cancer Res Treat.  2025 Jan;57(1):267-279. 10.4143/crt.2024.479.

Assessing the Efficacy of Bortezomib and Dexamethasone for Induction and Maintenance Therapy in Relapsed/Refractory Cutaneous T-Cell Lymphoma: A Phase II CISL1701/BIC Study

• Choi YS
• Shim J
• Kang KW
• Yoon SE
• Hong JS
• Lim SN
• Yhim HY
• Kwon JH
• Lee GW
• Yang DH
• Oh SY
• Shin HJ
• Eom HS
• Yoon DH
• Lee HG
• Jeong SH
• Kim WS
• Kim SJ

• KMID: 2564599
• DOI: http://doi.org/10.4143/crt.2024.479

Abstract

Purpose
This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea.
Materials and Methods
Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response.
Results
Thirteen of the 29 patients (44.8%) achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression.
Conclusion
This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Keyword

Cutaneous T-cell lymphoma; Bortezomib; Dexamethasone; Relapsed/refractory; Treatment efficacy; Safety profile

Figure

• 

  Fig. 1. CONSORT diagram and pattern of tumor response. (A) Flowchart of participants in the BIC study. (B) Swimmer plot showing duration of the study treatment and tumor responses. (C) Best change from baseline in skin by mSWAT scoring system. Bar color reflects global response according to global response criteria. AMI, acute myocardial infarction; CR, complete response; CTCL, cutaneous T-cell lymphoma; LyP, lymphomatoid papulosis; MF, mycosis fungoides; mSWAT, modified Severity-Weighted Assessment Tool; PC-ALCL, primary cutaneous anaplastic large cell lymphoma; PR, partial response; PTCL-NOS, peripheral T-cell lymphoma, unspecified; SD, stable disease.

• 

  Fig. 2. Antitumor activity and survival outcomes of the study treatment in patients with cutaneous T-cell lymphomas. (A) Tumor response in representative advanced mycosis fungoides patients with erythrodermic and tumor stage presentations. (B) The Kaplan-Meier curves of progression-free survival (PFS) in the intention-to-treat (ITT) population (n=29). (C) The Kaplan-Meier curves of PFS in responders (n=13) and non-responders (n=16). (D) The Kaplan-Meier curves of overall survival (OS) in the ITT population. CI, confidence interval.

• 

  Fig. 3. Landscape of somatic alterations in patients with cutaneous T-cell lymphomas (CTCLs). (A) Heatmap showing the most frequent genetic alteration in patients with relapsed or refractory CTCLs prior to initiating treatment with bortezomib and dexamethasone. Each column represents a distinct patient. (B) Longitudinal analysis of treatment-induced genomic profile changes. The heatmap illustrates the evolution of genomic profiles under the influence of bortezomib and dexamethasone treatment in patients with relapsed or refractory CTCLs. CR, complete response; LyP, lymphomatoid papulosis; MF, mycosis fungoides; MTOR, mammalian target of rapamycin; PC-ALCL, primary cutaneous anaplastic large cell lymphoma; PD, progressive disease; PFS, progression-free survival; PI3K, phosphoinositide 3-kinase; PR, partial response; PTCL-NOS, peripheral T-cell lymphoma, unspecified; SD, stable disease; Tx, therapy.

Reference

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