Pivekimab Sunirine in Blastic Plasmacytoid Dendritic Cell Neoplasm
Abstract
PURPOSE Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a unique myeloid malignancy with CD123 interleukin-3 receptor-α overexpression and poor prognosis. METHODS This phase I/II, open-label, multicenter study evaluated pivekimab sunirine (PVEK), a novel CD123 antibody-drug conjugate, 0.045 mg/kg once every 3 weeks, in adults with frontline (no previous systemic therapy and de novo BPDCN or coexisting hematologic malignancy) or relapsed/refractory BPDCN (ClinicalTrials.gov identifier: NCT03386513 ) The primary end point in the primary analysis population (PAP; frontline de novo) was composite complete response (CCR; CR+ clinical CR) rate. RESULTS Of 84 patients, 33 had frontline BPDCN (22 de novo [20 in PAP]; 11 with previous or concomitant malignancy) and 51 had relapsed/refractory disease. The median (range) age was 72 (63-76) years. In the PAP (n = 20), the CCR rate was 75% (95% CI, 51 to 91; n = 15; median duration: 10.6 [95% CI, 3.8 to not reached] months) and the median overall survival (OS) was 16.6 (95% CI, 7.2 to not reached) months. Eight of these 15 (53%) patients proceeded to stem-cell transplant (SCT). The corresponding rate for relapsed/refractory disease was 14% (95% CI, 6 to 26; n = 7; median duration: 9.2 [95% CI, 2.4 to not reached] months), and the median OS was 5.8 (95% CI, 3.9 to 8.4) months. Adverse events (AEs) included peripheral edema (54%), fatigue (26%), and infusion-related reactions (26%). Grade ≥3 events included neutropenia (16%), thrombocytopenia (14%), and peripheral edema (12%). Serious AEs included pneumonia (6%) and febrile neutropenia (5%). Two on-treatment cases of reversible veno-occlusive disease (VOD) occurred. Of the total 19 patients who proceeded to SCT, VOD was reported in five patients (four with relapsed/refractory BPDCN). CONCLUSION PVEK, with convenient dosing, led to high, durable responses, especially in frontline BPDCN, and a manageable safety profile.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (35)
Andrew A. Lane
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States
Luca Mazzarella
2Early Drug Development for Innovative Therapies Division, IRCCS IEO - Istituto Europeo di Oncologia, Milan, Italy
David A. Sallman
6Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL
Matthew L. Ulrickson
3Section of Hematology, Banner MD Anderson Cancer Center, Gilbert, AZ
Gary J. Schiller
David Geffen School of Medicine at UCLA, Los Angeles, California, United States
Harry P. Erba
Duke University, Durham, North Carolina, United States
Eunice S. Wang
30Roswell Park Cancer Institute, Buffalo, NY
Roland B. Walter
Daniel J. DeAngelo
1Dana-Farber Cancer Institute, Boston, MA
Yining Du
21AbbVie Inc., North Chicago, United States
Sribalaji Lakshmikanthan
AbbVie, Inc, North Chicago, IL
Jalaja Potluri
AbbVie Inc., North Chicago, IL, United States
Hagop M. Kantarjian
Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas USA
Naval G. Daver
Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas USA
Navel Daver
Naveen Pemmaraju
The University of Texas MD Anderson Cancer Center, Houston, Texas, United States
Eunice Wang
13Roswell Park Comprehensive Cancer Center, Buffalo, United States
Daniel Deangelo
2Dana Farber Cancer Institute, Boston, United States
Andrew Lane
2Broad Institute of MIT and Harvard, Cambridge, United States
Harry Erba
28Duke University Medical Center, Durham, United States
David Sallman
Moffitt Cancer Cancer and Research Institute, Tampa, Florida, United States
Roland Walter
1University of Washington, Medicine (Hematology/Oncology), Seattle, United States
Ahmed Aribi
1City of Hope, Duarte, United States
Matthew Ulrickson
28Banner MD Anderson Cancer Center, Gilbert, AZ
Gary Schiller
7David Geffen School of Medicine at UCLA, Los Angeles, United States
Pau Montesinos
Hospital Universitari i Politecnic La Fe, Valencia, Spain
Enrico Derenzini
17Oncohematology Division, IEO European Institute of Oncology IRCCS, Department of Health Sciences, University of Milan, Milan, Italy
Luca Mazzella
Maria Benedetta Giannini
9IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori, Meldola, Italy
Giovanni Martinelli
Giovanni Marconi
31Hematology Unit, Ospedale S. Maria delle Croci, University of Bologna, Ravenna, Italy
Eric Deconinck
14Hopital Jean Minjoz, Besancon, France
Ollivier Legrand
14Hôpital Saint-Antoine, Service d'hématologie clinique et de thérapie cellulaire, Paris, France
Delphine Lebon
10CHU Amiens Picardie, Unité d'Hématologie clinique et Thérapie Cellulaire, Amiens, France
Valerio Maisano
7Department of Hematology, Institut Paoli-Calmettes, INSERM UMR 1068, CNRS UMR725, CNRS, Aix-Marseille University, Marseille, France