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

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

  • J Hematol Oncol. 2021 Feb 24;14(1):35. doi: 10.1186/s13045-020-01004-y.
Robert J Kreitman 1,  Claire Dearden 2,  Pier Luigi Zinzani 3 4,  Julio Delgado 5,  Tadeusz Robak 6,  Philipp D le Coutre 7,  Bjørn T Gjertsen 8,  Xavier Troussard 9,  Gail J Roboz 10,  Lionel Karlin 11,  Douglas E Gladstone 12,  Nataliya Kuptsova-Clarkson 13,  Shiyao Liu 14,  Priti Patel 14,  Federico Rotolo 15,  Emmanuel Mitry 15,  Ira Pastan 16,  Francis Giles 17,  Study 1053 investigators
Affiliations

Affiliations

  • 1 Clinical Immunotherapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA. kreitmar@mail.nih.gov.
  • 2 The Royal Marsden Hospital, Downs Road, Sutton, England, UK.
  • 3 Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, Bologna, Italia.
  • 4 Istituto di Ematologia, "Seràgnoli", Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università Degli Studi, Bologna, Italia.
  • 5 Hospital Clinic Barcelona, IDIBAPS, Barcelona, Spain.
  • 6 Medical University of Łódź and Copernicus Memorial Hospital, Pabianicka 62, 90-001, Łódź, Poland.
  • 7 Charité - Universitätsmedizin Berlin, Charitépl. 1, 10117, Berlin, Germany.
  • 8 Haukeland University Hospital and University of Bergen, Jonas Lies vei 65, 5021, Bergen, Norway.
  • 9 Hospital Center University of Caen Normandie, Avenue de La Côte de Nacre, 14000, Caen, France.
  • 10 Weill Cornell Medical College, The New York Presbyterian Hospital, 525 E 68th St, New York, NY, USA.
  • 11 Hôpital Lyon Sud, Hospices Civils de Lyon, 165 Chemin du Grand Revoyet, 69310 Pierre-Bénite, Lyon, France.
  • 12 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, 401 N Broadway, Baltimore, MD, USA.
  • 13 AstraZeneca, One MedImmune Way, Gaithersburg, MD, USA.
  • 14 Acerta Pharma (AstraZeneca), 121 Oyster Point Blvd, South San Francisco, CA, USA.
  • 15 Innate Pharma, 117 Avenue de Luminy, BP 30191, 13276, Marseille, France.
  • 16 Clinical Immunotherapy Section, Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
  • 17 Developmental Therapeutics Consortium, 175 E Delaware Pl #7204, Chicago, IL, USA.
PMID: 33627164 DOI: 10.1186/s13045-020-01004-y
Abstract

Background: Moxetumomab 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).

Methods: Eligible 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.

Results: Eighty 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.

Conclusions: Moxetumomab 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 registration: ClinicalTrials.gov identifier: NCT01829711; first submitted: April 9, 2013. https://clinicaltrials.gov/ct2/show/NCT01829711.

Keywords

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

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