Abstract 4288

Resistance to imatinib could be overcome by new generations of TKIs. Data about the efficacy of second line TKI treatment may help to create a system for prognosing the duration of 2nd line TKI treatment and time of switching from second line TKI treatment to hematopoietic stem cell transplantation.

The aim of the study was to evaluate the results of 2nd line TKI treatment in patients resistant or intolerant to imatinib.

Patients and methods

44 resistant and 3 intolerant to imatinib pts were included. Cytogenetics with G-banding and PCR with sequencing were performed for evaluation the response and mutations. There were 39, 7 and 1 pts in CP, AP and BP respectively, Patients were treated by three different ATP-pocket inhibitors. The follow-up on 2nd line TKIs was 0.9-48mons (Median - 15.9 mons), median follow-up from diagnosis was 73,9 mons. In prognosis analysis (CHR, cytogenetics, Sokal) intolerant patients were not included.

Results

Probability of overall survival from diagnosis by 10 years was 85%. Probability of survival from the start of TKI2 by 4 y -90%. There were no differences in survival in pts with primary and secondary resistance, in CP and AP. Patients with low and intermediate Sokal risk did better than patients with high risk (p=0.014, Fig. 1.).

8 pts had T315I mutation when studied on second line TKI therapy.

Achievement of CCyR was 50% (58% when T3151 patients were excluded), it was higher in low+intermediate in comparison with high risk pts (60% vs 30%, p=0.091), in CP than in AP (56% vs 20%,p=0.07), in patients with CHR at switching than in those without CHR (72% vs 18%, p=0.014). We failed to find any differences in CCyR achievement in pts with different best cytogenetic response on imatinib (complete, major, minor, minimal responses, absence of cytogenetic response).

MCyR depended on the type of resistance - it was higher in secondary, than in primary resistant pts (80% vs 45%,p=0.06, Fig2). Probability of MCCyR loss was 20%, all of them appear during the first year of treatment. It was higher in AP than in CP (40% vs 12%,P=0.04).

Probability of 4 years PFS was high - 75%, also without differences in primary vs secondary resistance and even in AP vs CP.

Conclusion

Second line TKI treatment is very efficacious in imatinib resistant pts. The effect depended on the type of resistance and phase of the disease, CHR at the moment of switching to 2nd line treatment.

Disclosures:

No relevant conflicts of interest to declare.

Topics:
protein-tyrosine kinase inhibitor, russia, brachial plexus neuritis, imatinib mesylate, follow-up, g-banding, hematopoietic stem cell transplantation, polymerase chain reaction

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2009 by The American Society of Hematology
2009
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