title: First line treatment with newer tyrosine kinase inhibitors in chronic myeloid leukemia associated with deep and durable molecular response - systematic review and meta-analysis.
abstract: BACKGROUND
  The choice of a specific tyrosine kinase inhibitor (TKI) as first line treatment in chronic myeloid leukemia (CML) is complex and influenced by multiple factors. We published a meta-analysis examining the role of newer TKIs as first line treatment in chronic phase CML. In view of the recently published data, we decided to update it.
  
  
  METHODS
  We conducted a systematic review and meta-analysis of randomized controlled trials comparing first line treatment with imatinib to the newer TKIs (nilotinib, dasatinib, bosutinib and ponatinib). We searched MEDLINE, conference proceedings and databases of ongoing trials up to August 2015.
  
  
  RESULTS
  Our search yielded eight trials including 3554 patients. Treatment with the newer TKIs significantly improved major molecular response (MMR) at all time points and increased the rate of complete molecular response (CMR) at 12 and 24 months [relative risk (RR) 2.58, 95% CI 1.98-3.37, six trials and RR 2.05, 95% CI 1.63-2.58, three trials, respectively]. Early molecular response at three months was better with the newer TKIs (RR 1.33, 95% CI 1.26-1.40, six trials). Importantly, progression rate to accelerated or blastic phase was significantly lower with the newer TKIs at 12, 24 months and 5 years. Yet, there was no difference in all-cause mortality. The risk of adverse events requiring treatment discontinuation increased with the newer TKIs.
  
  
  CONCLUSIONS
  With a longer follow-up, the newer TKIs remain more potent than imatinib, yet with no significant effect on survival. As CMR is a prerequisite for treatment discontinuation and cure, the newer TKIs favor treatment cessation.
authors: a Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center , Petah-Tikva , Israel.|c Sackler School of Medicine, Tel Aviv University , Tel Aviv , Israel.
authors: Ronit
authors: R
authors: Gurion
authors: a Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center , Petah-Tikva , Israel.|c Sackler School of Medicine, Tel Aviv University , Tel Aviv , Israel.
authors: Pia
authors: P
authors: Raanani
authors: a Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center , Petah-Tikva , Israel.|c Sackler School of Medicine, Tel Aviv University , Tel Aviv , Israel.
authors: Liat
authors: L
authors: Vidal
authors: a Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center , Petah-Tikva , Israel.|c Sackler School of Medicine, Tel Aviv University , Tel Aviv , Israel.
authors: Avi
authors: A
authors: Leader
authors: a Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center , Petah-Tikva , Israel.|b Internal Medicine Department A , Rabin Medical Center , Petah-Tikva , Israel.|c Sackler School of Medicine, Tel Aviv University , Tel Aviv , Israel.
authors: Anat
authors: A
authors: Gafter-Gvili
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000069439:Dasatinib / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D007093:Imidazoles / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D028761:Withholding Treatment
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; D011743:Pyrimidines; C545373:ponatinib; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib