Chronic Myeloid Leukemia Philadelphia Chromosome Positive (CML Ph+) with Imatinib (IM) Intolerance or Resistant Disease. Response to Thalidomide (TALI) Treatment. Preliminary Report of a Serial of Cases with Encouraging Results

Abstract 1689

The increase dose of Imatinib, the shift to a Tyrosine Kinase (TKI) inhibitor of second generation or hematopoietic stem cell transplantation are treatment options when there is loss or lack of response to IM in CML; However, in patients without access to these therapeutic alternatives, the use of alkylating drugs or investigational agents is indicated. NF Kappa B pathway is constitutively activated in CML patients therefore the combination of IM with a NF Kappa B inhibitor (as thalidomide) contributes a new very interesting field of research. We treated 21 patients (11 female) with CML Ph +⁻ resistant (n=13) or intolerant (n=8) to IM, mean +⁻ SD age was 44 + 11 years. At diagnosis 16 (79%) were classified as high risk, according with Eutos scale. Mean +⁻ SD time of IM treatment before adding thalidomide (100mg daily) was 47.8 +⁻ 31 months. At the time of this preliminary analysis, mean follow up since thalidomide addition was 5 (1–18 months) and only 13 patients are evaluable for response (Global response rate was 76%): Six had hematological response & Four achieved complete cytogenetic response (CCgR). The first case was a 53 year old female, who started treatment with IM in accelerated phase, was intolerant to IM and neither achieve CCgR with IM, but reached it after 6 months of adding thalidomide and remains with this treatment after 18 months. The second case was a 38 year old female, who achieved CCgR after 6 months within IM treatment, lasted 53 months, and finally thalidomide was added after losing CCgR; she achieved a 2^nd CCgR after 7 months with this combination, and continues with thalidomide at 11 months. The third one is a 44 year old female, who only achieved partial CCgR (pCGR), and after indicating thalidomide on accelerated phase, she had CCgR after 4 months of this drug and remains at 6 months of treatment. Finally, the fourth case is a 26 year old female that received thalidomide because of a suboptimal response to IM; she achieved CCgR after 2 months within thalidomide. Eight patients are not evaluable for response yet, but are ongoing and all will be detailed at ASH meeting. Toxicity has been acceptable, mainly grade 1 neurotoxicity & none severe adverse events have been documented. This is the first communication of the use of Thalidomide with Imatinib with promising results which may represent an alternative therapeutic in CML with antiproliferative enhancer and/or synergistic effect in patients with resistance to IM without opportunity of access to other treatments. This cases report open a future very interesting field of research in intolerance and resistance CML.