Patients with Accelerated-Phase Chronic Myeloid Leukemia at Diagnosis Benefit from Tyrosine Kinase Inhibitor Therapy at Treatment Outset

Patients with accelerated-phase chronic myeloid leukemia at diagnosis may benefit from immediate tyrosine kinase inhibitor therapy rather than alternate treatments.

Tyrosine kinase inhibitor (TKI) therapy may produce better outcomes in patients presenting with accelerated-phase chronic myeloid leukemia (CML-AP) at their initial diagnosis, according to research published in the April 2014 edition of Clinical Lymphoma Myeloma and Leukemia.

“Patients who present with features of CML-AP at the time of diagnosis have an excellent outcome with frontline therapy with TKIs, particularly with 2GTKIs [second-generation TKIs],” the researchers wrote. “….Thus, patients who present with features of CML-AP at the time of diagnosis can be offered therapy with TKIs and do not need an SCT [stem cell transplant].”

Between 5% and 10 % of patients present with CML-AP at the time of diagnosis, the researchers noted. Despite this, most studies on TKI therapy in patients in the accelerated phase include patients who received the therapy after their prior treatments failed.

The study cohort included 51 adult patients with a confirmed accelerated-phase CML diagnosis who received TKIs as initial therapy in consecutive or parallel clinical trials. Complete blood counts were obtained every 1 to 2 weeks during the first 2 to 3 months of the study, and then every 4 to 6 weeks thereafter.

Thirty participants received imatinib therapy initially, 16 participants received nilotinib, and 5 received dasatinib. Among participants treated with imatinib, 5 received a 400-mg/day initial dose, 21 received a 600-mg/day initial dose, 3 received an 800-mg/day initial dose, and 1 received a 1000-mg/day initial dose. Participants receiving nilotinib received 800 mg daily, and participants receiving dasatinib received 100 mg daily.

At median follow-up of 65 months, 96% of all participants achieved complete hematologic response at a median time of 1 month. Major cytogenetic response was seen in 86% of participants overall.

In the imatinib group, the rate of complete cytogenetic response was 80%. Meanwhile, 69% of participants in that therapy arm achieved major molecular response, and 49% of participants achieved molecular response.

Thirty-two percent of participants receiving dasatinib achieved complete cytogenetic response, whereas 21% of nilotinib participants achieved the same measure. Participants receiving nilotinib also had a major molecular response rate of 11%.

Only 9 participants died during follow-up: 8 who received imatinib, and 1 from the combined nilotinib and dasatinib cohort. Only 2 of the deaths in the imatinib cohort could be attributed to CML, however. The remaining 6 deaths were attributed to comorbidities or unknown causes.

The projected overall survival at 36 months was 87% for participants receiving imatinib and 95% for those receiving either nilotinib or dasatinib.

“The survival advantage with 2GTKI then might be related to longer follow-up with the corresponding greater time at risk for deaths from other causes,” the researchers wrote. “Thus, although 2GTKIs provide a trend for better response rate, because of the smaller cohort size, we cannot categorically conclude that 2GTKI should be recommended over imatinib; however, we can conclude that TKIs should be the standard of care for all patients with de novo CML-AP.”

At the last follow-up, 59% of participants were still using the TKI they were initially prescribed. Eight participants progressed to blast phase of the disease and discontinued therapy, and 5 discontinued therapy because of resistance. The remaining participants discontinued therapy for other reasons, including noncompliance, patient choice, and difficulties obtaining their therapy.