Clinical Significance of Myelosuppression Associated with the Use of Dasatinib and Nilotinib As Initial Therapy in Chronic Phase (CP) of Chronic Myeloid Leukemia (CML)

Autor: Alfonso Quintás-Cardama, Hagop M. Kantarjian, Jan A. Burger, Susan O'Brien, Jorge E. Cortes, Elizabeth M. Burton, Long Xuan Trinh, Elias Jabbour, Theresa Liu-Dumlao, Farhad Ravandi, Yesid Alvarado, Alessandra Ferrajoli
Rok vydání: 2011
Předmět:
Zdroj: Blood. 118:2761-2761
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v118.21.2761.2761
Popis: Abstract 2761 Background: Frontline treatment with tyrosine kinase inhibitors (TKIs) has improved prognosis for patients with chronic myelogenous leukemia (CML). Myelosuppression is the most common adverse event (AE) seen during therapy with frontline second generation TKIs, dasatinib and nilotinib. The impact that grade 3/4 myelosuppression has on future outcome has not been described. Aim: To define the patient characteristics and clinical significance of myelosuppression associated with the use of dasatinib or nilotinib as initial therapy for CML. Methods: From August 2005, 204 patients (pts) diagnosed with CML-CP were treated with dasatinib (n=99) or nilotinib (n=105) in parallel trials. Prior imatinib exposure of less than 4 weeks was allowed. Complete blood counts (CBC) and differentials were done weekly in the first month, every 1–2 months up to the first year, every 3–4 months in the second year, and every 4–6 months thereafter. Results: A total of 44 (42%) pts developed grade 3/4 myelosuppression (MS) defined under CTCAE v4.0 criteria as hemoglobin (Hb) Of the 44 patients with MS, 39 (89%) experienced the event for the first time within 3 months from initiation of therapy. Five (11%) experienced the event after the first 3 months of treatment: 2 eventually came off study (one for resistance and the other for disease progression, both on nilotinib), and 3 (all on dasatinib) continued on therapy, able to achieve CMR. Complications associated with MS included hospitalization in 2 pts (one for pneumonia, and another for flu and prolonged QTc); 6 (14%) required antibiotics; 2 (5%) required blood transfusions; and 2 (5%) required growth factors (erythropoietin). MS led to TKI dose reduction in 9% of all pts treated (41% of those with MS), including 13% of those on dasatinib, and 5% of those on nilotinib. Dose reduction resolved MS in most instances. Recurrence of MS was seen in 10 pts, 2 of whom had progression of disease to blast phase/AML. The outcome of pts with MS is described in table 1 compared to those without MS. Patients with MS had a significantly lower rate of CCyR, MMR, CMR and EFS compared to those without MS. Conclusion: MS is a common AE among pts receiving therapy with dasatinib or nilotinib as initial therapy for CML that frequently leads to dose reductions, and is associated with an inferior outcome. Whether the worse outcome reflects decreased dose intensity, or whether the outcome and decreased tolerance to therapy reflect an intrinsic difference in disease biology remains to be determined. Disclosures: Kantarjian: BMS: Research Funding; Novartis: Research Funding. Quintas-Cardama:Novartis: Consultancy; BMS: Consultancy. Jabbour:Novartis: Honoraria; Pfizer: Honoraria; BMS: Honoraria. Ravandi:Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria. Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding.
Databáze: OpenAIRE
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