TY - JOUR
T1 - Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia
AU - Kreitman, Robert J.
AU - Dearden, Claire
AU - Zinzani, Pier Luigi
AU - Delgado, Julio
AU - Karlin, Lionel
AU - Robak, Tadeusz
AU - Gladstone, Douglas E.
AU - le Coutre, Philipp
AU - Dietrich, Sascha
AU - Gotic, Mirjana
AU - Larratt, Loree
AU - Offner, Fritz
AU - Schiller, Gary
AU - Swords, Ronan
AU - Bacon, Larry
AU - Bocchia, Monica
AU - Bouabdallah, Krimo
AU - Breems, Dimitri A.
AU - Cortelezzi, Agostino
AU - Dinner, Shira
AU - Doubek, Michael
AU - Gjertsen, Bjorn Tore
AU - Gobbi, Marco
AU - Hellmann, Andrzej
AU - Lepretre, Stephane
AU - Maloisel, Frederic
AU - Ravandi, Farhad
AU - Rousselot, Philippe
AU - Rummel, Mathias
AU - Siddiqi, Tanya
AU - Tadmor, Tamar
AU - Troussard, Xavier
AU - Yi, Cecilia Arana
AU - Saglio, Giuseppe
AU - Roboz, Gail J.
AU - Balic, Kemal
AU - Standifer, Nathan
AU - He, Peng
AU - Marshall, Shannon
AU - Wilson, Wyndham
AU - Pastan, Ira
AU - Yao, Nai Shun
AU - Giles, Francis
N1 - Funding Information:
Conflict of interest This study was sponsored by MedImmune. RJK received a research grant from MedImmune and is co-inventor of moxetumomab pasudotox, with the NIH holding the patent. CD has received personal fees from Gilead, Infinity, Janssen/Pharacyclics, MedImmune, Roche, and Sanofi Aventis, and has received clinical trial support from MedImmune. PLZ has served as an advisor for Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, Roche, Servier, and Takeda. JD served on a data monitoring board for Med-Immune, has received research grants from Janssen and Roche, and has received personal fees from Abbvie, Gilead, Janssen, and Roche. LK, DEG, M Gotic, LL, FO, RS, GS, SD, LB, CAY, AH, KB, MB, MG, AC, MD, SD, SL, MR, PR, TT, GS, GJR, XT, and WW have no conflicts to report. TR has received research grants from AstraZeneca. PLC has served as a speaker for Bristol-Myers Squibb, Incyte, Novartis, and Pfizer. DAB has received personal fees from Amgen, Novartis, and Teva, and his institution has received reimbursement for clinical trials from Ablynx, Amgen, Astellas, Astex, Cyclacel, Gen-zyme, Janssen, MedImmune, Merus, Menarini, Novella Clinical, Pfizer, and Seattle Genetics. BTG has received personal fees from BerGenBio AS, Novartis AS, Pfizer, and Seattle Genetics, received non-financial support from Merck Sharpe & Dohme and Roche, and owns shares in Alden Cancer Therapeutics 2 AS and Kinn Therapeutics AS. FM has received research grants from Amgen and Sandoz, received travel accommodations from Octapharma and Roche, and served on advisory boards for Pfizer, Roche, and Sandoz. FR has received research grants from MedImmune. TS has served on speakers’ bureaus for Pharmacyclics and Seattle Genetics, and on a steering committee for Juno. KB, NS, PH, SM, and NSY are employees of MedImmune and may own stock/options in AstraZe-neca. IP is co-inventor of moxetumomab pasudotox, with the NIH holding the patent. FG has received a research grant from MedImmune.
Funding Information:
Acknowledgements This study was sponsored in part by the National Cancer Institute Intramural Program. We thank the patients and their families who participated in this study. We also thank Elad Sharon, MD, MPH, for study monitoring during the CTEP-sponsored portion of the study, Julie Feurtado, RN, for collecting and reporting a portion of the study data, Sangmin Lee and Jiří Mayer for serving as investigators during the study, all investigational site personnel, and the MedImmune team, including Jamie Freeman, Mark Lanasa, Monica Hernandez, and Carolyn Pendry. Medical writing and editorial assistance were provided by Amy Zannikos, PharmD, of Peloton Advantage, Parsippany, NJ, and were funded by MedImmune.
Funding Information:
This study and manuscript were funded by MedImmune, the global biologics R&D arm of AstraZeneca. MedImmune employees were involved in the study design, the collection, analysis, and interpretation of data, the review of the manuscript, and the decision to submit for publication.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/8/1
Y1 - 2018/8/1
N2 - This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status. Among 80 patients (79% males; median age, 60.0 years), durable complete response (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial response) was 75%; 64 patients (80%) achieved hematologic remission. Among complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and generally manageable with supportive care and treatment discontinuation (6 patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of independently assessed durable response and MRD eradication in heavily pretreated patients with HCL, with acceptable tolerability.
AB - This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status. Among 80 patients (79% males; median age, 60.0 years), durable complete response (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial response) was 75%; 64 patients (80%) achieved hematologic remission. Among complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and generally manageable with supportive care and treatment discontinuation (6 patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of independently assessed durable response and MRD eradication in heavily pretreated patients with HCL, with acceptable tolerability.
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U2 - 10.1038/s41375-018-0210-1
DO - 10.1038/s41375-018-0210-1
M3 - Article
C2 - 30030507
AN - SCOPUS:85050272095
VL - 32
SP - 1768
EP - 1777
JO - Leukemia
JF - Leukemia
SN - 0887-6924
IS - 8
ER -