Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre, open-label, single-arm, phase 2 study - 03/12/24

Doi : 10.1016/S1470-2045(24)00503-5

Pier Luigi Zinzani, ProfMD ^a,⁎ , Koji Izutsu, MD ^b, Neha Mehta-Shah, MD ^c, Stefan K Barta, MD ^d, Kenji Ishitsuka, ProfMD ^e, Raul Córdoba, MD ^f, Shigeru Kusumoto, MD ^g, Emmanuel Bachy, MD ^h, Kate Cwynarski, PhD ⁱ, Giuseppe Gritti, MD ^j, Anca Prica, MD ^k, Eric Jacobsen, MD ^l, Tatyana Feldman, MD ^m, Yann Guillermin, MD ⁿ, Daisuke Ennishi, MD ^o, Dok Hyun Yoon, MD ^p, Eva Domingo Domenech, MD ^q, Jasmine Zain, ProfMD ^r, Jie Wang, MD ^s, Jin Seok Kim, ProfMD ^t, Marjolein van der Poel, MD ^u, Jin Jin, PhD ^v, Sutan Wu, PhD ^v, Yang Chen, PhD ^v, Takaya Moriyama, MD ^v, Ai Inoue, MD ^v, Keiko Nakajima, MD ^v, Steven M Horwitz, MD ^w

^a Lymphoma and Chronic Lymphoproliferative Syndromes Unit, Institute of Hematology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy

^b Department of Hematology, National Cancer Center Hospital, Tokyo, Japan

^c School of Medicine, Washington University, St Louis, MO, USA

^d Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

^e Department of Hematology and Rheumatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

^f Health Research Institute IIS-FJD, Fundacion Jimenez Diaz University Hospital, Madrid, Spain

^g Department of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

^h Department of Hematology, Lyon-Sud Hospital Center, Pierre-Bénite, France

ⁱ Research Department of Haematology, University College London Hospital, London, UK

^j Hematology and BMT Unit, ASST Papa Giovanni XXIII, Bergamo, Italy

^k Cancer Clinical Research Unit, University Health Network, Toronto, ON, Canada

^l Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

^m Lymphoma Division, Hackensack Meridian Health, Hackensack University Medical Center, Hackensack, NJ, USA

ⁿ Department of Hematology, Léon Bérard Center, Lyon, France

^o Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan

^p Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

^q Department of Hematology, Institut Catalá d'Oncologia, Hospital Duran I Reynals, IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain

^r Department of Hematology and Hematopoetic Stem Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA

^s Department of Medicine, Duke Cancer Center, Durham, NC, USA

^t Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea

^u Department of Internal Medicine, Division of Hematology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands

^v Daiichi Sankyo, Basking Ridge, NJ, USA

^w Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

^* Correspondence to: Prof Pier Luigi Zinzani, Lymphoma and Chronic Lymphoproliferative Syndromes Unit, Institute of Hematology “L. e A. Seràgnoli”, University of Bologna, 40138 Bologna, Italy Lymphoma and Chronic Lymphoproliferative Syndromes Unit Institute of Hematology “L. e A. Seràgnoli” University of Bologna Bologna 40138 Italy

Summary

Background

Peripheral T-cell lymphomas are aggressive non-Hodgkin lymphomas with few treatment options for relapsed or refractory disease. Valemetostat tosylate (valemetostat) is a potent, novel, dual inhibitor of EZH2 and EZH1. We investigated the clinical activity and safety of valemetostat in patients with relapsed or refractory peripheral T-cell lymphoma, and its safety in patients with relapsed or refractory adult T-cell leukaemia/lymphoma.

Methods

VALENTINE-PTCL01 was a multicentre, open-label, single-arm, phase 2 trial performed at 47 hospitals in 12 countries across Asia, Europe, North America, and Oceania. Patients with either peripheral T-cell lymphoma or adult T-cell leukaemia/lymphoma, aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0–2 received oral valemetostat at 200 mg per day in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint for patients with peripheral T-cell lymphoma was the CT-based objective response rate by blinded independent central review (BICR) using 2014 Lugano response criteria. Patients who received valemetostat and had a confirmed eligible peripheral T-cell lymphoma subtype on central review were included in the efficacy analysis. The primary endpoint for patients with adult T-cell leukaemia/lymphoma was the safety and tolerability of valemetostat. Safety in both cohorts was assessed in all patients who received at least one dose of valemetostat. The trial is registered with ClinicalTrials.gov, NCT04703192, and EudraCT, 2020-004954-31, and is closed to enrolment.

Findings

Between June 16, 2021, and Aug 10, 2022, 133 patients with relapsed or refractory peripheral T-cell lymphoma (median age 69·0 years [IQR 58·0–74·0]; 91 [68%] were male, and 42 [32%] were female) and 22 patients with adult T-cell leukaemia/lymphoma (66·5 years [54·0–73·0]; 15 [68%] were male, and seven [32%] were female) were enrolled. The median follow-up time was 12·3 months (95% CI 11·8–13·8). 52 (44%; 95% CI 35–53) of 119 efficacy-evaluable patients with relapsed or refractory peripheral T-cell lymphoma had an objective response. The most common grade 3−4 adverse events were thrombocytopenia (31 [23%] of 133 patients in the peripheral T-cell lymphoma group and 11 [50%] of 22 patients in the adult T-cell leukaemia/lymphoma group), anaemia (25 [19%] and ten [46%]), and neutropenia (23 [17%] and four [18%]). Serious treatment-emergent adverse events were reported in 53 (40%) patients with peripheral T-cell lymphoma and 15 (68%) patients with adult T-cell leukaemia/lymphoma; nine (7%) patients and one (5%) patient had a serious treatment-emergent adverse event considered to be treatment related, respectively. No treatment-related deaths were reported.

Interpretation

These data show that treatment with valemetostat leads to durable responses in patients with relapsed or refractory peripheral T-cell lymphoma, with a manageable safety profile.

Funding

Daiichi Sankyo.

Le texte complet de cet article est disponible en PDF.

Plan

Introduction

Methods

Study design and participants

Procedures

Outcomes

Statistical analysis

Role of the funding source

Export

Vol 25 - N° 12

P. 1602-1613 - décembre 2024 Retour au numéro

Article précédent

Valemetostat monotherapy in patients with relapsed or refractory non-Hodgkin lymphoma: a first-in-human, multicentre, open-label, single-arm, phase 1 study
Dai Maruyama, Eric Jacobsen, Pierluigi Porcu, Pamela Allen, Kenji Ishitsuka, Shigeru Kusumoto, Tomoko Narita, Kensei Tobinai, Francine Foss, Kunihiro Tsukasaki, Tatyana Feldman, Yoshitaka Imaizumi, Koji Izutsu, Satoko Morishima, Nobuhiko Yamauchi, Junichiro Yuda, Jonathan E Brammer, Toyotaka Kawamata, Jia Ruan, Kisato Nosaka, Atae Utsunomiya, Jie Wang, Jasmine Zain, Yasuyuki Kakurai, Hideyuki Yamauchi, Yoshiyuki Hizukuri, Noha Biserna, Masaya Tachibana, Ai Inoue, Steven M Horwitz

| Article suivant

The current and future global burden of cancer among adolescents and young adults: a population-based study
Taylor Hughes, Andrew Harper, Sumit Gupta, A Lindsay Frazier, Winette T A van der Graaf, Florencia Moreno, Adedayo Joseph, Miranda M Fidler-Benaoudia

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre, open-label, single-arm, phase 2 study - 03/12/24

Summary

Background

Methods

Findings

Interpretation

Funding

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL