Rousselot et al1 recently reported on the According to Stop Imatinib (A-STIM) study evaluating the persistence of major molecular response (MMR) in patients with chronic-phase chronic myeloid leukemia (CP CML) who had discontinued imatinib after prolonged deep molecular remission. They found that 61% of the patients were still in MMR and were treatment free after 36 months, whereas those who lost MMR and restarted tyrosine kinase inhibitor (TKI) therapy all regained MMR. They concluded that loss of MMR is a safe criterion for restarting therapy after TKI discontinuation.

Merrill J Egorin,1,2,3 Dhvani D Shah,1 Susan M Christner,1 Mara A Yerk,4 Kristin A Komazec,4 Leonard R Appleman,2 Robert L Redner,2 Brian M Miller,5 and Jan H Beumer1,6

Abstract
AIMS

CDF Issues:
Government responds to Cancer Drugs Fund Petition on Blood Cancers

Whether cancer is maintained by a small number of stem cells or is composed of proliferating cells with approximate phenotypic equivalency is a central question in cancer biology1. In the stem cell hypothesis, relapse after treatment may occur by failure to eradicate cancer stem cells. Chronic myeloid leukaemia (CML) is quintessential to this hypothesis. CML is a myeloproliferative disorder that results from dysregulated tyrosine kinase activity of the fusion oncoprotein BCR–ABL.

Nature:

International Weekly Journal of Science

BCR-ABL1 mutations are a common, well-characterized mechanism of resistance to imatinib as first-line treatment of chronic myeloid leukemia in chronic phase (CML-CP). Less is known about mutation development during first-line treatment with dasatinib and nilotinib, despite increased use because of higher response rates compared with imatinib.

July 10, 2015 | Chronic Myeloid Leukemia, Hematologic Malignancies, Leukemia & Lymphoma

Patients with chronic myeloid leukemia (CML) undergoing treatment with dasatinib had a narrower spectrum of mutations in BCR-ABL1 compared to those treated with imatinib, according to a new study, a finding which could aid in selection of second-line treatments. -

Abstract
Nilotinib is a second-generation tyrosine kinase inhibitors that has been approved for the first-line treatment of chronic phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib vs. imatinib (ENESTnd). Apart from this registration study, very few data are currently available on nilotinib first-line. We report here the long-term, 6-year, results of the first investigator-sponsored, GIMEMA multicenter phase II, single-arm, trial with nilotinib 400 mg twice daily as first-line treatment in 73 chronic-phase chronic myeloid leukemia patients. Six-year overall survival and progression-free survival were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥ 2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose nilotinib (400 mg twice daily), highlighting the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052).