This link to entire posting. http://www.cmladvoca...de-effects#stop
• Below is the good news being reported in the "stopping TKI" arena:
Update on therapy discontinuation (STOP) studies
Dr Francois Mahon from France presented an update on the STIM1 study. In the study, patients were stopping therapy after sustained PCR negativity on Imatinib treatment for at least 2 years. After the stop, PCR was performed every month in the first year and every 2nd month thereafter, and recurrance was assumed when detectable PCR was following by a one-log increase in two successive assessment, or a los of MMR at any point in time. 100 patients were recruited into this study. 39% of patients maintained PCR negative at 60 months, with most relapses occured in the first 6 months and none after 24 months. Only Sokal risk score (based on age, spleen size, platelets and blasts at time of diagnosis) was predictive for molecular relapse, but not gender, prior interferon therapy, time from diagnosis to PCR negativity, duration of PCR negativity or duration of prior Imatinib therapy. When looking at the Sokal risk score, 47% of patients with low sokal risk score relapsed, while 73% with high Sokal risk score. Economically, the drug cost savings of the participants on trial was around 4.6 million EUR. The researchers again underlined that discontinuation should be proposed only in a clinical trial with strict molecular monitoring and long-term follow-up. (ASH-Abstract #255)
To assess less stringent failure criteria of therapy-free remission, the French group conducted the A-STIM ("According to STop-IMatinib") study. While eligibility criteria were similar to STIM1, loss of MMR (BCR-ABL >0,1%) was the criterion to restart treatment. Of 81 patients that discontinued, 51 (61%) were still in MMR without medication after a median of 31 months. Of these 51 patients, 45% were in sustained BCR-ABL negativity, 24% had occasional BCR-ABL positivity, and 31% had BCR-ABL fluctuations meaning at least 2 consecutive positive PCRs. Of those that relapsed, all patients regained MMR, but one patient experienced progression on Imatinib. In summary, the treatment-free remission rate is at 60% on Imatinib when MMR is the failure criterion, while only 40% on STIM1 study remained in remission. (ASH-Abstract #381)
Similar results like STIM1 were presented by the French group in the STIM2 study. In this study with 127 patients who had been PCR negative for at least 2 years, more than half (75 patients) remained in treatment-free remission. Of the 52 patients who had relapsed, 48 relapses accurred during the first 4 months, and 4 more relapses until month 9. Of the 75 patients that remained treatment-free, 40 patients had detectable PCR above MR4.5 for short periods (= fluctuating PCR results), but did not relapse. The researchers conclude that positive fluctuation of PCR results on very low molecular levels do not lead to CML relapse or progression, therefore complete eradication of residual leukemic stem cells may not be necessary to discontinue Imatinib therapy in deep molecular response of at least 2 years duration. (ASH-Abstract #654)
The Nordic CML study group presented first findings from an immunology substudy of the EURO-SKI trial. Their research suggests that patients who relapse after TKI discontinuation may have a lower proportion of natural killer cells and their functioning at the time of drug discontinuation. While mechanisms need to be further investigated to predict individual relapse after discontinuation, targeting these mechanism might also lead to improved treatment-free rates in the future. (ASH-Abstract #379)