Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial

Journal of Hematology & Oncology

Priti Patel¹  Shiyao Liu¹  Nataliya Kuptsova-Clarkson²  Pier Luigi Zinzani³  Philipp D. le Coutre⁴  Robert J. Kreitman⁵  Ira Pastan⁵  Francis Giles⁶  Bjørn T. Gjertsen⁷  Xavier Troussard⁸  Julio Delgado⁹  Lionel Karlin^1,10  Federico Rotolo^1,11  Emmanuel Mitry^1,11  Tadeusz Robak^1,12  Douglas E. Gladstone^1,13  Claire Dearden^1,14  Gail J. Roboz^1,15 

[1] Acerta Pharma (AstraZeneca), 121 Oyster Point Blvd, South San Francisco, CA, USA;AstraZeneca, One MedImmune Way, Gaithersburg, MD, USA;Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italia;Istituto di Ematologia, “Seràgnoli”, Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università Degli Studi, Bologna, Italia;Charité – Universitätsmedizin Berlin, Charitépl. 1, 10117, Berlin, Germany;Clinical Immunotherapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, 20892, Bethesda, MD, USA;Developmental Therapeutics Consortium, 175 E Delaware Pl #7204, Chicago, IL, USA;Haukeland University Hospital and University of Bergen, Jonas Lies vei 65, 5021, Bergen, Norway;Hospital Center University of Caen Normandie, Avenue de La Côte de Nacre, 14000, Caen, France;Hospital Clinic Barcelona, IDIBAPS, Barcelona, Spain;Hôpital Lyon Sud, Hospices Civils de Lyon, 165 Chemin du Grand Revoyet, 69310 Pierre-Bénite, Lyon, France;Innate Pharma, BP 30191, 117 Avenue de Luminy, 13276, Marseille, France;Medical University of Łódź and Copernicus Memorial Hospital, Pabianicka 62, 90-001, Łódź, Poland;Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 401 N Broadway, Baltimore, MD, USA;The Royal Marsden Hospital, Downs Road, Sutton, England, UK;Weill Cornell Medical College, The New York Presbyterian Hospital, 525 E 68th St, New York, NY, USA;

关键词: Hairy cell leukemia (HCL);    B cell malignancy;    Relapsed/refractory;    CD22;    Immunotoxin;    Moxetumomab pasudotox;    Minimal residual disease (MRD);   

DOI  :  10.1186/s13045-020-01004-y

来源: Springer

【 摘 要 】

BackgroundMoxetumomab pasudotox is a recombinant CD22-targeting immunotoxin. Here, we present the long-term follow-up analysis of the pivotal, multicenter, open-label trial (NCT01829711) of moxetumomab pasudotox in patients with relapsed/refractory (R/R) hairy cell leukemia (HCL).MethodsEligible patients had received ≥ 2 prior systemic therapies, including ≥ 2 purine nucleoside analogs (PNAs), or ≥ 1 PNA followed by rituximab or a BRAF inhibitor. Patients received 40 µg/kg moxetumomab pasudotox intravenously on Days 1, 3, and 5 of each 28-day cycle for up to six cycles. Disease response and minimal residual disease (MRD) status were determined by blinded independent central review. The primary endpoint was durable complete response (CR), defined as achieving CR with hematologic remission (HR, blood counts for CR) lasting > 180 days.ResultsEighty adult patients were treated with moxetumomab pasudotox and 63% completed six cycles. Patients had received a median of three lines of prior systemic therapy; 49% were PNA-refractory, and 38% were unfit for PNA retreatment. At a median follow-up of 24.6 months, the durable CR rate (CR with HR > 180 days) was 36% (29 patients; 95% confidence interval: 26–48%); CR with HR ≥ 360 days was 33%, and overall CR was 41%. Twenty-seven complete responders (82%) were MRD-negative (34% of all patients). CR lasting ≥ 60 months was 61%, and the median progression-free survival without the loss of HR was 71.7 months. Hemolytic uremic and capillary leak syndromes were each reported in ≤ 10% of patients, and ≤ 5% had grade 3–4 events; these events were generally reversible. No treatment-related deaths were reported.ConclusionsMoxetumomab pasudotox resulted in a high rate of durable responses and MRD negativity in heavily pre-treated patients with HCL, with a manageable safety profile. Thus, it represents a new and viable treatment option for patients with R/R HCL, who currently lack adequate therapy.Trial registrationClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711

【 授权许可】

CC BY