Survival and Response Outcomes to Different Treatment Schedules in CML Patients Starting Therapy with Imatinib. Results from the CML Spanish Registry (RELMC)

The RELMC is a multicentric, 17-hospitals-based cancer registry whose aim is to describe the treatments received by patients with CML, their outcomes, and the variables that influence treatment choices.

To study the response and survival outcomes, in newly diagnosed CML patients treated with Imatinib (Im) as first line treatment.

249 newly diagnosed CML patients have been included. They are distributed in the following subgroups according to treatments received Im400. 166 patients received only Im400.

1. Im400-HDIm: 33 pts received Im 400, followed by high dose Im (600 or 800).

2. Im400-HDIm-2GTKI: 16 pts received Im400, followed by high dose Im (600 or 800), and then 2^nd generation TKI.

3. HDIm: 14 pts received high dose Im only.

4. Im400-2GTKI: 20 pts received Im 400, followed by 2^nd generation TKI.

A summary of response and outcome is included in Table 1.

Complete cytogenetic response with regards to the best response, the CCyR rate was lower in patients with Im400-HDIm-2GTKI (60%) and Im400-2GTKI (62%). The rates were 84% in Im400, 83% in Im400-HDIm and 85% in HDIm; P Chi2 8,381(a) p=0,079. The CCyR cumulative incidence was also lower in patients with Im400-HDIm-2GTKI and Im400-2GTKI in comparison to the other groups, although second line response was faster in patients who changed to 2GTKI after Im400. The frequency of CCyR as best response in the Hasford high risk patients was low in all groups (66%,50%,50%,50&55%).

Major molecular response MMR as best response was lower in patients with Im400-HDIm-2GTKI (50%) and Im400-2GTKI (47%). The rates were 83%, 81% and 77% in the Im400, Im400-HDIm and HDIm groups respectively; P Chi2 19,4(a)p=0,001. The MMR cumulative incidence was higher in the HDIm group, lower in those treated with Im400-HDIm-2GTKI, and intermediate and similar in the other three groups. MMR as best response in the Hasford high risk patients was also low in all groups (60%, 75%, 50%, 50% & 33%).

Complete molecular response regarding best response, the CMR rate was lower in patients with Im400-HDIm-2GTKI (37,5%), Im400-2GTKI (31,6%) and Im400-HDIm (34%). In the other groups, the rate was 48% (Im400), and 72% (HDIm); P Chi2 17,4(a) p=0,002. The CMR cumulative incidence was higher in the HDIm group, and nil in those treated with Im400-HDIm-2GTKI.

Salvage therapy after suboptimal response (SR) or Failure (F). Two-thirds of patients with SR or F were able to obtain an optimal response and avoid transformation with a timely therapy change. All but one of the options (Im400-HDIm-2GTKI group) were similarly effective.

6 patients progressed (2,4%) (4 AP, 2 BC), and died; 6 patients changed to allo BMT and were censored; 6 patients died of non-CML related causes.

• Imatinib-based regimes obtained a high rate of response (genetic and molecular) in the majority of patients.

• Optimal response was obtained in 2/3 of the patients if high dose Im or a 2^nd G TKI is used as salvage therapy.

• In our series, patients treated upfront with HD Im obtained an earlier major or complete molecular response.

• Patients with failure had a better outcome if the 2^nd G TKI was introduced earlier.

• Hasford high risk pts. showed worse outcome regardless of treatment chosen.

• At least 2/3 of patients maintained optimal response at the end of the study

Palomera:Janssen Cilag: Honoraria. Steegmann:Bristol-Myers Squibb: Honoraria, Participated in advisory boards, Research Funding; Novartis: Participated in advisory boards, Research Funding.