BCR-ABL Transcript Type Predicts TKI Response in CML
Patients with chronic phase chronic myeloid leukemia who have e13a2 BCR-ABL transcripts display inferior outcomes when treated with imatinib.
Patients with chronic myeloid leukemia (CML) in chronic phase who have e13a2 BCR-ABL transcripts have inferior outcomes when treated with imatinib 400 mg, while those with e14a2 have favorable outcomes regardless of tyrosine kinase inhibitor (TKI) therapy, a study published in the journal Blood.1
The most common BCR-ABL transcripts in CML are e13a2 (b2a2) and e14a2 (b3a2), but it is unknown how the transcript type affects response and survival following initial treatment with different TKIs.
For the study, researchers included 481 patients with CML in chronic phase expressing various BCR-ABL transcripts. Of those, 42% expressed e13a2, 41% expressed e14a2, and 18% expressed both types.
Results showed that the proportion of patients with e13a2, e14a2, and both transcript types achieving complete cytogenetic response at 3 and 6 months was 59%, 67%, and 63%, and 73%, 81%, and 82%, respectively. Major molecular response rates were 27%, 49%, and 50% at 3 months, 42%, 67%, and 70% at 6 months, and 55%, 83%, and 76% at 12 months, respectively.
Researchers found that that in multivariate analysis, having e14a2 and both e13a2 and e14a2 predicted for optimal responses at 3, 6, and 12 months. In addition, the expression of e14a2 or both predicted for longer event-free and transformation-free survival.
Those patients also achieved earlier and deeper responses compared with those with only e13a2 transcripts, and having e14a2, either alone or in concomitant with e13a2, predicted for optimal ELN responses at all 3 time points.
- Jain P, Kantarjian H, Patel KP, et al. Impact of BCR-ABL transcript type on response and survival in patients with chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors [published online ahead of print January 4, 2015]. Blood. doi: 10.1182/blood-2015-10-674242.