BCR/ABL Transcript At 3 Months Predicts Long-Term Outcomes Following Second Generation Tyrosine Kinase Inhibitor Therapy in the Patients with CML in Chronic Phase Who Failed Imatinib.

The BCR/ABL transcript level at 3 months can predict long-term outcomes following frontline therapy with Imatinib or Dasatinib in chronic myeloid leukemia (CML) patients. However, data is lacking with second generation tyrosine kinase inhibitor (2GTKI) therapy after Imatinib failure.

A total of 112 patients with CML in chronic phase (CP) receiving 2GTKI after Imatinib failure were reviewed. Treatment outcomes including complete cytogenetic (CCyR), major molecular (MMR) and molecular response 4.5 (MR^4.5), treatment failure, progression-free (PFS) and overall survival (OS) were compared according to BCR/ABL transcript levels at 3 or 6 months, divided into <1%^IS, 1–10%^IS and °Ã10%^IS.

Using cut off of 1%^IS and 10%^IS BCR/ABL transcript level, 70 patients (65%) showed <1%^IS of BCR/ABL transcript level at 3 months, 16 patients (15%) between 1 and 10%^IS, and 21 patients (20%), °Ã10%^IS at 3 months. BCR/ABL transcript level at 3 months showed better correlation with OS (p<0.001) than that at 6 months (p=0.147). Better OS was also observed in the patients achieving <1%^IS (100%) and 1–10%^IS (100%) than those with °Ã10%^IS at 3 months (70.6%, p<0.001). Those with <1%^IS exhibited the best CCyR (100% at 12 months), MMR (93.1±3.2% at 18 months) and MR^4.5 (80.2±6.3% at 3 years); those with 1–10%^IS, intermediate (56.4±15.5% CCyR at 12 months; 22.1±14.1% MMR at 18 months; 10.0±9.5% MR^4.5 at 3 years); and those with °Ã10%^IS, the lowest CCyR (16.7±11.2% at 12 months), MMR (6.2±6.1% at 18 months) and MR^4.5 rates (0%). Especially, in the subgroup of Imatinib resistant patients (n=59), none of them achieved MR^4.5 if BCR/ABL transcript level is above 1% at 3 months (i.e. those with 1–10%^IS or °Ã10%^IS). Multivariate analysis confirmed strong correlation of BCR/ABL transcript level at 3 months with CCyR (HR 0.019), MMR (HR 0.047), MR^4.5 (HR 0.057), treatment failure (HR 12.264), PFS (HR 7.754) and OS (HR 15.115). The group with <1%^IS at 3 months maintained significantly lower BCR/ABL transcript level compared to other 2 groups.

The BCR/ABL transcript level at 3 months is the most relevant surrogate for outcomes following 2GTKI therapy after Imatinib failure.

Figure 1.

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Comparison of cumulative incidences of response and probability of freedom from treatment failure to 2GTKI in overall (A to D)

Figure 1.

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Comparison of cumulative incidences of response and probability of freedom from treatment failure to 2GTKI in overall (A to D)

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No relevant conflicts of interest to declare.