Tyrosine Kinase Inhibitors as Initial Therapy for Patients With Chronic Myeloid Leukemia in Accelerated Phase

Abstract

Background Accelerated phase CML (CML-AP) most frequently represents a progression state in CML. However, some patients present with AP features at the time of diagnosis. There is limited information on the outcome of these patients when receiving tyrosine kinase inhibitors (TKI) as initial therapy. Methods We analyzed the outcome of 51 consecutive patients with CML who presented with features of AP at the time of diagnosis, including blasts ≥15% (n=6), basophils ≥20%, (n=22), platelets <100×109/L (n=3), cytogenetic clonal evolution (n=17), or more than 1 feature (n=3). Patients received initial therapy with imatinib (n=30), dasatinib (n=5) or nilotinib (n=16). Results The rate of complete cytogenetic response (CCyR) for patients treated with imatinib was 80%, and with dasatinib or nilotinib was 90%. Major molecular response (MMR, BCR-ABL/ABL ≤0.1%, by International Scale [IS]) was achieved in 69% including complete molecular responses (MR4.5, BCR-ABL/ABL ≤0.0032% IS) in 49%. MMR rates for patients treated with imatinib were 63%, and with second generation TKI (2GTKIs) 76%. Overall survival at 36 months was 87% with imatinib and 95% with 2GTKI’s. Conclusion TKIs should be considered standard initial therapy for patients with AP at the time of diagnosis.

Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015

“…68, 73 The optimal therapeutic approach in AP-CML differs according to whether the patient is TKI-naïve or has progressed from chronic phase while taking a TKI. Eighty to ninety percent of treatment-naïve patients will achieve CCyR with TKI 93, 94 and have a similar EFS and OS to patients presenting in chronic phase, particularly when treated with 2 nd generation TKI. Those patients with cytogenetic clonal evolution as the only criterion for AP also have superior outcomes to those with hematologic/clinical features of AP.…”

“…There is no randomized data to guide the choice or dose of TKI. However, there is a suggestion from non-randomized studies that 2 nd generation TKIs have superior response rates to imatinib 93 , and ponatinib provides perhaps the best outcome.…”

Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management

“…Patients with cytogenetic clonal evolution as the only AP criterion have a long-term event-free survival rate of about 60% [84]. Otherwise, TKIs provide hematologic responses in 80% of patients and an estimated 4-year survival rates of 40-55% in AP CML, but only a 40% response rate and a median survival of 9-12 months in BP CML.…”

“…Patients with de novo CML AP have a better outcome with front-line TKI therapy than patients who evolve from chronic to AP. The estimated 6-8 year survival rates with TKI therapy in de novo AP CML are 60-80% [84]. Such patients may continue on TKI therapy as their long-term treatment if they achieve a CCyR on TKI therapy.…”

Chronic Myeloid Leukemia–Transplantation in the Tyrosine Kinase Era

“…25 2GTKIs show promise in achieving better responses (MMR 76%), although with only small numbers of patients described to date. 26 At present, durable response rates remain too low to confidently withhold HSCT in eligible patients. Jiang and colleagues 27 suggested a risk-stratification algorithm capable of identifying low-risk patients in whom HSCT conferred no advantage over imatinib (6-year OS 81% vs 100%), but these patients constituted less than 1 in 3 AP patients.…”