Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease.

Abstract

PURPOSE:

More than half of patients with chronic-phase chronic myelogenous leukemia (CP-CML) in complete molecular response (CMR) experience molecular relapse after imatinib discontinuation. We investigated loss of major molecular response (MMR) as a criterion for resuming therapy.

PATIENTS AND METHODS:

A multicenter observational study (A-STIM [According to Stop Imatinib]) evaluating MMR persistence was conducted in 80 patients with CP-CML who had stopped imatinib after prolonged CMR.

RESULTS:

Median time from imatinib initiation to discontinuation was 79 months (range, 30 to 145 months);median duration of CMR before imatinib discontinuation was 41 months (range, 24 to 96 months); median follow-up after discontinuation was 31 months (range, 8 to 92 months). Twenty-nine patients (36%) lost MMR after a median of 4 months off therapy (range, 2 to 17 months). Cumulative incidence of MMR loss was estimated as 35% (95% CI, 25% to 46%) at 12 months and 36% (95% CI, 26% to 47%) at 24 months, whereas probability of losing CMR was higher. Fluctuation of BCR-ABL transcript levels below the MMR threshold (≥ two consecutive positive values) was observed in 31% of patients after imatinib discontinuation. Treatment-free remission was estimated as 64% (95% CI, 54% to 75%) at 12 and 24 months and 61% (95% CI, 51% to 73%) at 36 months. Median to time to second CMR was estimated as 7.3 months in re-treated patients.

CONCLUSION:

Loss of MMR is a practical and safe criterion for restarting therapy in patients with CML with prolonged CMR.

• Authors: Philippe Rousselot, Aude Charbonnier, Pascale Cony-Makhoul, Philippe Agape, Franck E Nicolini, Bruno Varet, Martine Gardembas, Gabriel Etienne, Delphine Réa, Lydia Roy, Martine Escoffre-Barbe, Agnès Guerci-Bresler, Michel Tulliez, Stéphane Prost, Marc Spentchian, Jean Michel Cayuela, Josy Reiffers, Jean Claude Chomel, Ali Turhan, Joëlle Guilhot, François Guilhot, François-Xavier Mahon
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 5 Pg. 424-30 (Feb 10 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 24323036 (Publication Type: Journal Article, Multicenter Study, Observational Study)

Chemical References

• Antineoplastic Agents
• BCR-ABL1 fusion protein, human
• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Imatinib Mesylate
• Fusion Proteins, bcr-abl

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects)
• Benzamides (administration & dosage, adverse effects)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• France
• Fusion Proteins, bcr-abl (antagonists & inhibitors, genetics, metabolism)
• Humans
• Imatinib Mesylate
• Kaplan-Meier Estimate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy, enzymology, genetics, mortality, pathology)
• Male
• Middle Aged
• Molecular Targeted Therapy
• Piperazines (administration & dosage, adverse effects)
• Protein Kinase Inhibitors (administration & dosage, adverse effects)
• Pyrimidines (administration & dosage, adverse effects)
• Recurrence
• Remission Induction
• Risk Factors
• Time Factors
• Treatment Outcome
• Young Adult