Page 72 - Haematologica August 2018

Correspondence:
gar2001@med.cornell.edu
Received: October 26, 2017. Accepted: April 27, 2018. Pre-published: May 3, 2018.
doi:10.3324/haematol.2017.183418
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/8/1308
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Haematologica 2018 Volume 103(8):1308-1316
1Division of Hematology and Medical Oncology, Leukemia Program, Weill Cornell Medicine/New York-Presbyterian Hospital and 2Division of Biostatistics and Epidemiology, Weill Cornell Medicine, New York, NY, USA
Ferrata Storti Foundation
Acute Myeloid Leukemia
Phase I trial of plerixafor combined with decitabine in newly diagnosed older patients with acute myeloid leukemia
Gail J. Roboz,1 Ellen K. Ritchie,1 Yulia Dault,1 Linda Lam,1 Danielle C. Marshall,1 Nicole M. Cruz,1 Hsiao-Ting C. Hsu,1 Duane C. Hassane,1 Paul J. Christos,2 Cindy Ippoliti,1 Joseph M. Scandura1 and Monica L. Guzman1
ABSTRACT
Acute myeloid leukemia carries a dismal prognosis in older patients. The objective of this study was to investigate the safety and effi- cacy of decitabine combined with the CXCR4 antagonist plerix- afor in newly diagnosed older patients with acute myeloid leukemia and to evaluate the effects of plerixafor on leukemia stem cells. Patients were treated with monthly cycles of decitabine 20 mg/m2 days 1-10 and esca- lating doses of plerixafor (320-810 mcg/kg) days 1-5. Sixty-nine patients were treated, with an overall response rate of 43%. Adverse karyotype did not predict response (P=0.31). Prior hypomethylating agent treatment was the strongest independent predictor of adverse overall survival (haz- ard ratio 3.1; 95%CI: 1.3-7.3; P=0.008) and response (14% in previously treated patients, 46% in treatment naïve; P=0.002). As expected, the most common toxicities were myelosuppression and infection. Plerixafor induced mobilization of leukemia stem and progenitor cells, but did not cause clinically significant hyperleukocytosis. Reduction in leukemia stem cells appeared to correlate with duration of response. Plerixafor can be safely added to decitabine in poor-prognosis, elderly acute myeloid leukemia patients. The maximum tolerated dose of the combination was 810 mcg/kg. While mobilization of leukemia stem cells was observed in some patients, the clinical benefit of adding plerixafor was uncertain. This trial was registered at clinicaltrials.gov identifier: 01352650.
Introduction
Acute myeloid leukemia (AML) carries a dismal prognosis in older patients, espe- cially those with adverse cytogenetics and/or poor performance status. The median age at diagnosis is 67 years, with 5-year survival less than 10%.1 Standard induction chemotherapy with cytarabine and an anthracycline can achieve remission in selected older AML patients, but this regimen is often not feasible due to toxicity and poor tolerability. Furthermore, long-term survival after initial intensive chemotherapy is rare in these patients, even in the setting of initial complete remis- sion (CR). Decitabine (5-aza-2’-deoxycytidine), a DNA methyltransferase inhibitor, has shown efficacy with an acceptable extramedullary toxicity profile in newly diagnosed older AML patients, with 25% CR, 7% 30-day mortality, and a median overall survival of 7.7 months when administered using a schedule of 20 mg/m2 over one hour (h) daily for five days. Of note, patients in this multicenter study received a median of 3 cycles of treatment (range 1-25 cycles).2 Blum et al. treated 53 AML patients with a median age of 74 years (range 60-85 years) with decitabine 20 mg/m2 daily for ten days every four weeks.3 The CR rate was 47% after a medi- an of 3 cycles of therapy, with 2% 30-day and 15% 8-week induction mortality, mostly due to disease progression. Median overall and disease-free survival were 55
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