Patients With Chronic Myeloid Leukemia Can Achieve Treatment-Free Remission After TKI Treatment

Treatment-free remission (TFR) is achievable in patients with chronic myeloid leukemia (CML) after treatment with tyrosine kinase inhibitors (TKIs) if they meet the criteria for safe TFR, with the potential to significantly improve quality of life, according to a presentation at the Hematology/Oncology Pharmacy Association conference 2022.

Presenters Adam J. DiPippo, PharmD, BCOP, and Jonathan Michael Savoy, PharmD, BCOP, both clinical pharmacy specialists of leukemia at the University of Texas MD Anderson Cancer Center, discussed the factors that help contribute to TFR success.

“It’s amazing to me when I sit back and think about what we’ve done with CML over a relatively short amount of time,” DiPippo said during the presentation. “We’ve taken a merely 100% fatal disease and turned it into a chronic medical condition in a matter of years with 1 type of drug therapy.”

When choosing a frontline treatment option for individuals, the first thing to consider is the clinical considerations of the drug and the patient, such as comorbidities, toxicity profile of the TKI, drug-drug interactions, and patient preference, according to the panelists.

From there, the Sokal score, which is used to stratify individuals with CML in chronic phase into low-, intermediate-, or high-risk groups for overall survival, is evaluated to determine whether a first generation TKI, such as imatinib, or a second generation TKI, such as bositinib, dasatinib, or nilotinib, are preferred. The Sokal score is based on blast percentage, spleen size, platelet count, and age.

If the individual is at intermediate- or high-risk, a second generation TKI is preferred and if they are at low risk, either a first or second generation TKI can be used. With risk stratification, approximately 50% to 60% of individuals who are low risk sustain TFR, whereas 10% to 20% of patients who are high risk sustain TFR, according to Sokal scores determined at diagnosis.

This is suggestive of adverse disease biology, despite optimal responses to therapy, according to the panel. Additionally, the findings around the duration of therapy have been inconclusive.

Longer duration of treatment does not necessarily predict better TFR outcomes. Currently, there is no optimal timeframe for therapy and there are ongoing studies that aim to identify this outcome. The studies to date only include individuals with at least 2 years of sustained remission and imatinib has the most data.

Those data could indicate that longer durations of therapy and longer time to molecular remission are associated with increased probability of successful TDR, but more data are needed to come to a definite conclusion.

“It’s possible to get similar rates of TFR in the second line as it is in the first line with the second generation TKIs,” Savoy said during the presentation.

Data also indicate that there is a higher TFR rate in individuals who receive interferon and imatinib compared to imatinib only. Higher TFR rates were also found in individuals with a longer duration of interferon exposure.

In terms of depth of response, there is no optimum major molecular response (MMR) duration and ongoing studies aim to look at its clinical implications. However, it is found that increased sensitivity to detect disease recurrence earlier can be a major advantage.

The molecular response should also be monitored at specific intervals with real-time quantitative polymerase chain reaction testing. The tests can be completed outside of specialized cancer centers and should be performed at the time of diagnosis, every 3 months until the BCR-ABL1 (IS) levels are at most 1%, or less, every 3 months for 2 years after achieving that BCR-ABL1 (IS) level, and every 3 to 6 months after.

It is also important to look at the long-term adverse events of TKI, which are cardiovascular toxicity, pulmonary toxicity, renal toxicity, and endocrine toxicity. It is also important to discuss the risk factors for TKI withdrawal syndrome with patients after they no longer need the therapy, according to the panel.

Reference

DiPippo A J, Savoy J M. Implementation of Treatment-Free Remission in Chronic Myeloid Leukemia. Hematology/Oncology Pharmacy Association Annual Conference 2022.; April 1, 2022; Boston, MA.