The BCR-ABL1 transcript type influences response and outcome in Philadelphia chromosome-positive chronic myeloid leukemia patients treated frontline with imatinib.

Abstract

The most frequent BCR-ABL1 fusion transcripts in chronic myeloid leukemia (CML) are the e13a2 (b2a2) and the e14a2 (b3a2) ones. In the imatinib era few studies addressing the prognostic significance of the BCR-ABL1 transcript type in early chronic phase CML have been published. Overall, these studies suggest that in e14a2 patients the response to imatinib is faster and deeper. To evaluate if the BCR-ABL1 transcript type (e13a2 compared to e14a2) affect the response to imatinib and the clinical outcome in newly diagnosed adult CML patients, 559 patients enrolled in 3 prospective studies (NCT00514488, NCT00510926, observational study CML/023) were analyzed. A qualitative PCR was performed at baseline: 52% patients had a e14a2 transcript, 37% a e13a2 transcript, 11% co-expressed both transcripts and 1% had other rare transcripts. The median follow-up was 76 months (95% of the patients had at least a 5-year observation). The complete cytogenetic response rates were comparable in e14a2 and e13a2 patients. The median time to MR3.0 (6 and 12 months) and MR4.0 (41 and 61 months) was significantly shorter for e14a2 patients compared to e13a2 patients, with a higher cumulative probability of MR3.0 (88% and 83%, P < .001) and MR4.0 (67% and 52%, P = .001). The 7-year overall survival (90% and 83%, P = .017), progression-free survival (89% and 81%, P = .005) and failure-free survival (71% and 54%, P < .001) were significantly better in patients with e14a2 transcript. In conclusion, patients with e13a2 transcript had a slower molecular response with inferior response rates to imatinib and a poorer long-term outcome.

• Authors: Fausto Castagnetti, Gabriele Gugliotta, Massimo Breccia, Alessandra Iurlo, Luciano Levato, Francesco Albano, Paolo Vigneri, Elisabetta Abruzzese, Giuseppe Rossi, Serena Rupoli, Francesco Cavazzini, Bruno Martino, Ester Orlandi, Patrizia Pregno, Mario Annunziata, Emilio Usala, Mario Tiribelli, Simona Sica, Massimiliano Bonifacio, Carmen Fava, Filippo Gherlinzoni, Monica Bocchia, Simona Soverini, Maria Teresa Bochicchio, Michele Cavo, Martinelli Giovanni, Giuseppe Saglio, Fabrizio Pane, Michele Baccarani, Gianantonio Rosti, GIMEMA CML Working Party
• Journal: American journal of hematology (Am J Hematol) Vol. 92 Issue 8 Pg. 797-805 (Aug 2017) ISSN: 1096-8652 [Electronic] United States
• PMID: 28466557 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Imatinib Mesylate
• Fusion Proteins, bcr-abl

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Female
• Fusion Proteins, bcr-abl (genetics)
• Humans
• Imatinib Mesylate (administration & dosage, therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (diagnosis, drug therapy, genetics, mortality)
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• Prognosis
• Proportional Hazards Models
• Protein Kinase Inhibitors (administration & dosage, therapeutic use)
• Transcription, Genetic
• Treatment Outcome
• Young Adult