Outcome and Prognosis of 1955 Patients with Chronic Myeloid Leukemia: First Results of the CML-Registry of the European Treatment and Outcome Study EUTOS.

Eligibility criteria were: diagnosis of chronic phase Ph+ or bcr/abl positive CML between 2002 and 2006, age ≥ 18 years, and start with any kind of imatinib-based treatment in a prospective study within six months after first diagnosis. For hematologic (HR), cytogenetic (CgR), and molecular (MR) remission the ELN criteria were used. Competing risk estimations and Landmark analyses were applied when indicated. Patients from the FI-LMC-group in France (n=526), Germany (n=644), Italy (n=513), The Netherlands (n=119), the Nordic Countries (Denmark, Finland, Norway, Sweden, n=140)) and Switzerland (n=13) were included (date: 07/11/2009), for an overall n of 1955 patients.

Median age was 52.5 years and 45% were female. The Euro prognostic score profile was for 38% of the patients low, for 51% intermediate and for 11% high risk. Imatinib 400 mg was allocated to 41%, Imatinib 600 mg to 8%, Imatinib 800 mg to 17%, and Imatinib-based combinations with IFN or Ara C to 34% of the patients. Median observation time was 24 months (range: 1-81). Complete hematologic remission (CHR) was finally achieved by 97%, complete cytogenetic remission (CCgR) by 94%, and major molecular remission (MMR) after 18 months by 62%. Overall survival (OS) after 60 months was 92%. Euro score clearly separated high risk vs. non high risk patients with regard to CHR (p=.0002), CCgR (p=.0023), but not for MMR, whereas Sokal score did so for CCgR (p<.0001). Deletion 9q did not show any impact on CHR, CCgR or MMR.

Using Landmark-analysis with those 1012 patients who provided complete data for CHR, CCgR and MMR, CHR within 6 months from day 1 of imatinib treatment showed an impact on the chance to achieve CCgR (96.1% vs. 87.5% p=.0003) and MMR at 18 month (56.1% vs. 48.5%, p=.087). CHR within 3 months did not show a relevant impact on CCgR and MMR. Partial CgR (Ph+ < 35%, n=725)) within 6 months was associated with a higher chance to achieve MMR at 18 month (62.8% vs. 51.4% p=.0003).

Patients who did not achieve CCgR within 3 (93%), 6 (70%), 12 (29%) or 18 (18%) months experienced an increasing risk for disease progression of 6%, 7%, 11% and 14% respectively but still showed a chance to eventually achieve CCgR of 87%, 83%, 60%, and 36%. Conclusions: This combined analysis of multinational European data showed very good response data regarding CHR, CCgR, MMR, and OS. Current prognostic CML scores seem to not separate prognosis of CML-patients sufficiently well. Early response markers like CHR and CgR after 6 months allow to differentiate the prognosis with regard to MMR but their clinical relevance may be questioned. Patients without CCgR within 6 months have a higher risk for disease progression and thus a closer follow up is indicated. With accumulating observation time the European CML Registry will allow to answer many clinically relevant questions about the prognostic value of early response markers.

Hasford:Novartis Pharma: Research Funding. Rosti:Novartis Pharma, Bristol Myers Squibb: Consultancy, Speakers Bureau. Baccarani:Novartis Pharma, Bristol Myers Squibb, Merck Sharp & Dome, Pfizer: Consultancy, Speakers Bureau. Montrucchio:Novartis Pharma : Employment. Rancati:Novartis Pharma: Employment. Simonsson:Novartis, BMS, Schering-Plough: Consultancy, Honoraria, Research Funding. Ossenkoppele:Novartis Pharma, BMS: Consultancy. Hehlmann:Novartis Pharma: Research Funding.