Completed Studies

Researchers discover why discontinuing TKI treatment may be successful for some but not others

Using the results of the Life After Stopping TKIs (LAST) study, researchers investigated the possibility of discontinuing TKI therapy among 172 patients who demonstrated a strong and sustained response to treatment. The study explains why this approach was successful for some but not others and details the impacts on patient quality of life.

CML is caused when pieces of two different chromosomes break off and switch places, creating an abnormal gene called BCR-ABL1. This gene then tells the body to create a protein called BCR-ABL. Doctors test levels of BCR-ABL throughout CML treatment to determine how their patients are responding to drug therapy.

This study found that the presence of the BCR-ABL protein at the time of treatment discontinuation may be predictive of molecular recurrence (MRec). Over a three-year period:

  • Patients with NO detectable levels of BCR-ABL at the time of treatment discontinuation had a 10% chance of MRec

  • Patients with detectable levels of BCR-ABL at the time of treatment discontinuation had a 50%-64% chance of MRec

These findings suggest that patients who do not have detectable levels of BCR-ABL at the time of treatment discontinuation may be able to safely scale back the number of monitoring appointments that they attend during treatment-free remission. Doing so may help reduce the stress and anxiety often felt by patients leading up to these check-ups.

During treatment-free remission, there were significant improvements in patient-reported symptoms:

  • 88% of patients had improvement in diarrhea

  • 80% of patients had improvement in fatigue

  • 35% of patients had improvement in depression

  • 21% of patients had improvement in sleep disturbance

  • 5% of patients had improvement in pain interference

The results of this study determined that TKI discontinuation was safe, and 61% of patients remained in treatment-free remission after 3 years.

Published in:

Atallah E, Schiffer CA, Radich JP, Weinfurt KP, Zhang MJ, Pinilla-Ibarz J, Kota V, Larson RA, Moore JO, Mauro MJ, Deininger MWN, Thompson JE, Oehler VG, Wadleigh M, Shah NP, Ritchie EK, Silver RT, Cortes J, Lin L, Visotcky A, Baim A, Harrell J, Helton B, Horowitz M, Flynn KE. Assessment of Outcomes After Stopping Tyrosine Kinase Inhibitors Among Patients With Chronic Myeloid Leukemia: A Nonrandomized Clinical Trial. JAMA Oncology. 2021 7(1):42-50.

 
 

Patients share the impacts of stopping TKI treatment to inform decisions of others

This report explains the results of the Life After Stopping TKIs (LAST) study regarding patient changes in function after stopping and restarting TKI treatment.

Patient-reported outcome measurements (PROMs) were collected from 172 chronic myeloid leukemia (CML) patients who discontinued drug therapy over a 36-month period. Of those who remained in treatment-free remission (TFR) at 12 months:

  • 92% reported improvement in social function

  • 71% reported improvements in social isolation

  • 10% reported improvements in satisfaction with sex life

  • 4% reported improvements in physical function

These results can aid patients and physicians in deciding to pursue treatment discontinuation. For those who remain in TFR, functional outcomes improved overall. However, functional outcomes began to worsen for those who restarted treatment.

Published in:

Schoenbeck KL, Atallah E, Lin L, Weinfurt KP, Cortes J, Deininger MWN, Kota V, Larson RA, Mauro MJ, Oehler VG, Pinilla-Ibarz J, Radich JP, Schiffer CA, Shah NP, Silver RT, Thompson JE, Flynn KE. Patient-Reported Functional Outcomes in Patients With Chronic Myeloid Leukemia After Stopping Tyrosine Kinase Inhibitors. J Natl Cancer Inst. 2022. 114(1):160-164.

 
 

Patients describe their experience with pain after stopping TKI treatment

This study describes patient-reported pain in people with chronic myeloid leukemia (CML) after discontinuing tyrosine kinase inhibitor (TKI) treatment.

For CML patients who respond well to TKI, discontinuation of the treatment may allow for achievement of treatment-free remission with improvement of treatment-related symptoms. However, discontinuing TKIs has been associated with physician-reported pain increases in some patients.

Within three months of discontinuation of treatment:

  • 20% of patients had a physician report pain on their behalf

  • 13% of patients self-reported a large increase in pain

  • 11% of patients began taking a new pain medication

Each of these events was classified as an increase in pain level. There was limited overlap in these measures (that is, few patients had more than one indicator of increased pain).

In total, 60/172 (34.9%) of patients had an increase in pain in the first three months following treatment discontinuation. At six months, pain had returned to a baseline level and continued to decrease beyond that.

Three patients restarted TKI therapy to treat their pain. However, the results of this study show that the pain level trajectory was similar in patients who did and did not restart TKI treatment. This information suggests that restarting TKI treatment may not be more effective at reducing pain than remaining off the treatment.

To remain in TFR, patients should consider the following to manage any discontinuation-associated pain they may experience:

  • Increased physical activity

  • Use of an analgesic or and/or anti-inflammatory pain medication

  • Behavioral/cognitive approaches to pain management

Published in:

Flynn KE, Atallah E, Lin L, Shah NP, Silver RT, Larson RA, Panilla-Ibarz J, Thompson JE, Oehler VG, Radich JP, Kota V, Mauro MJ, Schiffer CA, Cortes J, Weinfurt KP. Patient- and physician-reported pain after tyrosine kinase inhibitor discontinuation among patients with chronic myeloid leukemia. Haematologica. 2022.

 
 

HJKC3-0001

Patients share factors that influence their decision about stopping their TKI

The standard treatment for chronic myeloid leukemia (CML) is lifelong drug therapy. Multiple clinical trials have shown that some patients with a sustained response to tyrosine kinase inhibitor (TKI) treatment can safely stop therapy and remain in a treatment-free remission (TFR). The results of this study, reveal what patients think about stopping TKI treatment for CML. Researchers conducted in-person interviews with 22 patients, half of whom wanted to try stopping their TKI. Participants included men and women across the typical age range for patients with CML.

There were multiple factors relevant to their decision about stopping TKIs:

  • Thoughts about risk of relapse

  • Reducing side effects

  • Maintaining a treatment that’s working

  • Financial considerations

  • Thoughts about one’s age or social roles (e.g., being a caretaker)

  • Wanting to take fewer medications

  • Being reminded of having CML

  • Need for increased monitoring

Keep in Mind

Patients in this study were recruited from academic cancer centers only.  A larger study that includes patients from both academic and community sites would help confirm the findings.

Published in:

Flynn KE, Myers JM, D’Souza A, Schiffer CA, Thompson J, Atallah E. “Exploring patient decision-making regarding discontinuation of tyrosine kinase inhibitors for chronic myeloid leukemia.” The Oncologist. 2019. 24(9):1253-1258.

 
 

Patients help define CML cure and future research goals

A survey of patients with chronic myeloid leukemia (CML) provides a patient definition of cure in CML treatment and outlines patients’ priorities for future CML research.

Researchers surveyed 458 people with CML across the United States. The overwhelming majority of patients (90%) considered the definition of cure for CML as “permanently stopping any CML treatment with no evidence of disease.”

Only 3% considered cure to be “taking a pill daily.”

To reach a treatment-free remission, many patients reported a willingness to add a new therapy to their TKI.

Patients universally supported more research in CML, specifically in:

  • Stopping CML treatment

  • Side effects of CML treatment

  • CML not responding to treatment

  • Long term complications from treatment

Published in:

Flynn KE, Mauro MJ, George G, Hinman A, Baim A, Kota V, Larson RA, Lipton JH, Thompson JE, Wadleigh M, Atallah E. “Patients’ perspectives on the definition of cure in chronic myeloid leukemia.” Leukemia Research. 2019. 80:40-42.