Musculoskeletal Pain in Patients With Chronic Myeloid Leukemia After Tyrosine Kinase Inhibitor Therapy Cessation

Clinical trials have shown that for some patients with chronic myeloid leukemia in chronic phase receiving tyrosine kinase inhibitors (TKIs), treatment-free remission (TFR) is achievable and safe. TFR is now a treatment goal for select patients who have experienced a sustained deep molecular response. An expected result of TFR would be a decrease in the frequency or intensity of adverse events (AEs) associated with TKI therapy. Unexpectedly, however, some clinical trials have reported new or worsening AEs, typically described as musculoskeletal pain, in patients attempting TFR. These AEs are hypothesized to be a TKI withdrawal syndrome, although the underlying mechanism is not known. Overall, musculoskeletal pain has been reported in approximately 20% to 30% of patients attempting TFR and is typically transient and easily managed. TKI cessation would be expected to improve patients’ quality of life (QOL); however, in studies assessing QOL, patients have reported little change after ceasing TKI therapy, perhaps because they must tolerate long-term TKI therapy before they can attempt TFR. Here we review reports of musculoskeletal pain during TFR and changes in QOL after TKI cessation in clinical trials. As more patients attempt TFR in routine practice, the health care community will play an important role in helping these patients understand the benefits and risks of TFR, the effect it may have on their QOL, and the potential for musculoskeletal pain.