Abstract 3435

Background:

Albeit of well-known, dramatic improvements, there remain some questions to be solved around Ph+CML in treatment with tyrosine kinase inhibitors (TKI). Among these, the significance of the amount of minimal residual disease (MRD) measured by RT-PCR. For instance, loss of a so-called major molecular response (MMR) is claimed to be a Òsuboptimal responseÓ and following the ELN recommendations, a change in treatment should be considered in these patients.

Aims:

To evaluate the relevance of a loss of MMR in patients with complete cytogenetic response (CCR).

Study Group and Methods:

We have analized 81 patients treated with imatinib for CML in chronic phase with a median follow up of 66 months. 36 patients started imatinib after interferon failure and 45 as front line therapy. Major Molecular Response (MMR; BCR-ABL/ABL ratio<0.1% IS) at any time was achieved by 63 patients.

Results:

22 patients (34%) lost MMR (documented al least twice). The risk of losing MMR was higher in late MMR (>18 months) compared with those cases whose MMR came much earlier (<18 months): 70% vs 18% (p=. 000). We have found no correlation among the lost of MMR and classical prognostic factors (Sokal-Index, mutations at the TK domain or imatinib plasma levels). Of these 22 patients, 7 (32 %) recovered MMR later with no therapy changes, 8 (36%) experienced fluctuations in the BCR-ABL transcript-levels without losing CCR, 4 (19%) did not attain a MMR but remained in stable CRR, and 3 (13%) lost CCR. These regained MMR after being treated on second generation TKI. The results show how the stability of the early MMR is greater than late MMR (table1).

Conclusions:

In our experience, one third of the patients who lost MMR recovered it later on the same treatment. And only 13% went on to treatment failure. Perhaps some similar cases (after first losing MMR) should be closely monitored before a change in treatment. Also of note is, of course regarding only our experience, that the risk of a loss of MMR seems to be maximal in patients who achieve a late MMR.

Table 1.

Evolution of patients after lossing MMR

Early MMR (n= 9)Late MMR (n=13)
Recover MMR 45% (4) 23% (3) 
Fluctuations 33% (3) 38% (5) 
Remained in Suboptimal Response 11% (1) 23% (3) 
Lost CCR 11% (1) 15% (2) 
Early MMR (n= 9)Late MMR (n=13)
Recover MMR 45% (4) 23% (3) 
Fluctuations 33% (3) 38% (5) 
Remained in Suboptimal Response 11% (1) 23% (3) 
Lost CCR 11% (1) 15% (2) 
Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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