Treating Chronic Myeloid Leukemia | Goals in Ph+ CML | CML Alliance
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Treatment Goals in Ph+CMLTreatment Goals in Ph+CML

Today’s European LeukemiaNet (ELN) recommendations identify major molecular response (MMR) as an important component of achieving an optimal response in Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML).1 In addition, ELN recommendations support molecular monitoring as a routine standard of care for patients with Ph+ CML, as a way to measure minimal levels of residual disease.1

Residual disease can leave patients vulnerable to disease progression

Clinical evidence demonstrates that even with complete cytogenetic response (CCyR) at 12 months, residual disease can increase the incidence of disease progression.2,3 In 1 trial, significantly more patients with CCyR at 12 months had disease progression compared with patients who achieved both MMR and CCyR at 12 months.2 In a long-term follow-up of the IRIS trial, nearly 1 in 5 patients who achieved a CCyR lost their response, and 1 out of 33 patients with CCyR progressed to accelerated phase or blast crisis (AP/BC).3

MMR is a better indicator of long-term prognosis

Recent results from the ENESTnd trial, the first and largest head-to-head study designed to compare nilotinib with imatinib using MMR as the primary end point, demonstrated that the rates of MMR for nilotinib (44% for the 300-mg dose and 43% for the 400-mg dose) were nearly twice the rate of imatinib (22%) (P<0.001 for both comparisons).4 Moreover, the study showed that no patient who had an MMR progressed to AP/BC.4

Long-term follow up from the IRIS trial also demonstrates that patients achieving an MMR had improved long-term outcomes.3 For example, patients who achieved an MMR at 12 months had a 100% rate of progression-free survival.3 This is one reason why MMR has become the new optimal goal in the treatment of Ph+ CML. By selectively targeting Bcr-Abl to reduce residual disease and achieve MMR, it is now possible to prevent progression to AP/BC phase.


Next: Targeting Bcr-Abl in Ph+ CML


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References

  1. Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol. 2009;27(35):6041-6051.
  2. Deininger M, O’Brien SG, Guilhot F, et al. International randomized study of interferon and STI571 (IRIS) 8-year follow-up: sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase treated with imatinib. Poster presented at: 51st American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2009; New Orleans, LA.
  3. Iacobucci I, Saglio G, Rosti G, et al; for the GIMEMA Working Party on Chronic Myeloid Leukemia. Achieving a major molecular response at the time of a complete cytogenetic response (CCgR) predicts a better duration of CCgR in imatinib-treated chronic myeloid leukemia patients. Clin Cancer Res. 2006;12(10):3037-3042.
  4. Saglio G, Kim D-W, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251-2259.