Efficacy and safety of switching to nilotinib in patients with CML-CP in major molecular response to imatinib: results of a multicenter phase II trial (NILSw trial)

Int J Hematol. 2018 May;107(5):535-540. doi: 10.1007/s12185-018-2401-y. Epub 2018 Jan 23.

Abstract

We evaluated the efficacy and safety of switching to nilotinib in CML-CP patients who had achieved MMR with continuous detectable BCR-ABL1 transcript levels after long-term imatinib treatment. Patients who had achieved MMR, but not deep molecular response (DMR), after > 18 months from the initiation of imatinib received nilotinib 400 mg twice daily for up to 24 months. BCR-ABL1 transcript levels were assessed every 3 months. Thirty-eight patients with a median age of 57.5 years (range 22-76 years) were evaluated. Twenty-seven patients completed 24 months of nilotinib treatment; 11 discontinued nilotinib due to retraction of consent (three patients), loss of MMR (1), intolerance (3) or AEs (5). Twenty patients [52.6%, (90% CI 38.2-66.7%)] achieved DMR. The cumulative incidence of achieving DMR by the time of 3, 6, 9, 12, 15, 18, and 21 months was 22.9, 37.7, 47.0, 53.7, 53.7, 53.7, and 53.7%, respectively. Adverse events were consistent with those reported in other nilotinib studies. Patients experienced each of the following cardiovascular complications: atrial fibrillation (G2), chest tightness and dyspnea (G1), myocardial infarction (G2) and heart failure (G3) (n = 1 for each complication). This study indicates nilotinib achieves strong, rapid induction of DMR for patients who achieved MMR after long-term imatinib therapy.

Keywords: Chronic myelogeneous leukemia; Deep molecular response; Imatinib; Major molecular response; Nilotinib.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Cardiovascular Diseases / chemically induced
  • Drug Substitution*
  • Female
  • Humans
  • Imatinib Mesylate / therapeutic use*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Male
  • Middle Aged
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Safety
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Pyrimidines
  • Imatinib Mesylate
  • nilotinib