Treatment with nilotinib was more effective in inducing deep molecular response (MR 4.5) than imatinib for patients with chronic myeloid leukemia (CML), according to research findings presented at the European Hematology Association (EHA) 2022 Congress.
Given that the MR 4.5 milestone may relate to the likelihood of sustained deep molecular response, these results may mean nilotinib therapy, and perhaps the other second-generation tyrosine kinase inhibitors (TKIs), could be “the treatment of choice” for patients to achieve treatment-free remission (TFR), noted presenter Fabrizio Pane, MD, of the University of Naples in Italy.
“Despite the large body of literature data, the best treatment strategy to reach TFR is still poorly defined, and we still don’t know the percentage of patients who start treatment and eventually achieve this goal,” Dr. Pane said.
To further define treatment responses in CML, Dr. Pane and colleagues conducted a study to compare nilotinib, a second-generation TKI, and imatinib. Imatinib therapy was followed with nilotinib therapy in cases of nonoptimal response.
For the study, patients with CML were randomly assigned to either nilotinib (n=228) or imatinib (n=220), according to their Sokal risk score and country. The primary endpoints were MR 4.5 at 24 months and the rate of patients who remained in sustained TFR (≥MR 3.0) without molecular relapse at 12 months after achieving TFR. Molecular relapse was defined as the loss of major molecular response or confirmed loss of MR 3.0.
The mean age of the study population was 54.2 years. Sokal scores at baseline categorized 40.8% of patients as low risk, 42.6% of patients as intermediate risk, and 16.1% of patients as high risk. Additionally, 62.3%, 28.7%, and 9.0% of patients presented with a low-, intermediate-, or high-risk EUTOS (The European Treatment Outcome Study) Long-Term Survival (ELTS) score. Overall, patients had a median follow-up of 30.4 months.
Around one-fourth of patients (25.4%) who received imatinib but did not experience optimal response within the first 12 months switched to nilotinib according to the study protocol. At the data cutoff in February 2022, 59 patients stopped the protocol treatment. Reasons for ceasing therapy included death (n=24), toxicity (n=23), progression (n=9), uncontrolled second neoplasia (n=2), or protocol violation (n=1).
Of 304 patients who remained, 35 experienced a nonoptimal response to treatment. At 24 months, a total of 76 out of the 322 patients with an available molecular response reached MR 4.5, which occurred at a significantly higher frequency within the group randomly assigned to nilotinib (48 vs. 28; p=0.015).
According to Dr. Pane, it is still unclear whether TFR corresponds to the eradication of leukemia cells or rather to a functional balance between their growth potential and the host’s anti-leukemic control.
“In addition, we do not have any reliable marker to predict TFR,” Dr. Pane stated, adding that this should be investigated in future studies.
Any conflicts of interest by the authors were made public at the time of presentation.
Reference
Pane F, Castagnetti F, Luciano L, et al. International, prospective study comparing nilotinib versus imatinib with early switch to nilotinib to obtain sustained treatment-free remission in patients with chronic myeloid leukemia. Abstract S156. Presented at the European Hematology Association (EHA) 2022 Congress, June 12, 2022; Vienna, Austria.
