Safety and Efficacy of Tinostamustine in a Subpopulation of Patients With Relapsed/Refractory Hodgkin Lymphoma From a Phase I Trial

IF 3.3 4区医学 Q2 HEMATOLOGY

Hematological Oncology Pub Date : 2024-12-01 DOI:10.1002/hon.70000

Anna Sureda, Antonio Pinto, Hervé Ghesquières, Franck Morschhauser, Olivier Tournilhac, Pim Mutsaers, Josée M. Zijlstra, Rosaria De Filippi, Kasia Hilgier, Nick Manamley, Tomas Janik, Pier Luigi Zinzani

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引用次数: 0

Abstract

A significant unmet need remains for patients with Hodgkin lymphoma (HL) who fail to respond to first-line treatment or experience an early relapse. Tinostamustine, a novel alkylating deacetylase inhibitor, inhibits tumor cell growth and slows disease progression in models of hematological malignancies and solid tumors. This was a Phase I, multicenter, open-label, two-stage trial investigating the safety and efficacy of tinostamustine in patients ≥ 18 years with relapsed/refractory (R/R) hematological malignancies, including HL. Stage 1 involved dose-escalation to determine the maximum tolerated dose (MTD) of tinostamustine, optimal infusion time and recommended Phase II dose (RP2D). Stage 2 confirmed the safety and efficacy of the RP2D in expansion cohorts of selected R/R hematological malignancies. Ten patients with heavily pre-treated HL entered dose-escalation, with nine patients experiencing treatment-emergent adverse events (TEAEs) considered to be related to study treatment—primarily hematological toxicities. MTD was 100 mg/m² tinostamustine over 60 min and signals of efficacy were observed for patients with HL. In Stage 2, all 20 patients with HL experienced ≥ 1 TEAE, which were principally hematological or gastrointestinal. There were no tinostamustine-related deaths in either stage of the study. Overall response rate in Stage 2 was 37% (2 complete responses, 5 partial responses; 95% confidence interval [CI]: 16%, 62%) and median progression-free survival 3.8 months (95% CI: 2.2–9.4 months). Tinostamustine is a promising new therapeutic approach for the treatment of patients with R/R classical HL with limited options. This study demonstrates a predictable and manageable safety profile with signals of efficacy.

Trial Registration: ClinicalTrials.gov identifier: NCT02576496

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来源期刊

Hematological Oncology 医学-血液学

CiteScore

4.20

自引率

6.10%

发文量

147

审稿时长

>12 weeks

期刊介绍： Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged: -Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders -Diagnostic investigations, including imaging and laboratory assays -Epidemiology, pathology and pathobiology of hematological neoplasia of hematological diseases -Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies -Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems. Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.