Management of adverse events associated with bosutinib treatment of chronic-phase chronic myeloid leukemia: expert panel review

Abstract

Bosutinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI), has been available for several years as a treatment for chronic-, accelerated-, and blast-phase chronic myeloid leukemia (CML), for patients with resistance or intolerance to prior therapy. In 2017, the BFORE trial demonstrated efficacy of bosutinib as first-line treatment in adult patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). The most common adverse events (AEs) of any grade in bosutinib-treated patients in BFORE were diarrhea, nausea, thrombocytopenia, increased alanine aminotransferase, and increased aspartate aminotransferase, consistent with the most commonly reported AEs in earlier studies. To balance the efficacy and tolerability of treatment to optimize patient adherence with medications, treating physicians commonly use various strategies such as initiating treatment at a lower dose, dose reduction, or dose interruption, depending on the type and severity of the AEs and the clinical setting. In light of the recent data from first-line treatment, an expert panel of hematologists reviewed management strategies for the use of bosutinib in treatment of CP-CML and made the recommendations reported here. Although the panel focused on first-line treatment, the principles can be for the most part extended to bosutinib use in later lines of treatment. Recommendations include advice regarding prophylaxis and management for diarrhea. The panel also considered optimum timing for referral to a specialist for specific AEs. Across the commonly occurring AEs, the panel highlighted the importance of education and communication with patients about anticipated AEs.

Clinical Importance of Drug Adherence during Tyrosine Kinase Inhibitor Therapy for Chronic Myelogenous Leukemia in Chronic Phase

“…After switching from IM to NILO, the total number of ADEs decreased in most cases. Although new ADEs developed initially after switching to NILO, tolerance was acquired by management of ADEs [3,15]. In particular, fluid retention, digestive symptoms, and muscle symptoms including facial edema, peripheral edema, lids edema, general fatigue, depression, nausea, muscle pain and muscle cramps induced by IM were reduced significantly ( Fig.…”

“…These results might be due to the difference in drug adherence between the TKI groups. It has been reported that the Morisky high adherence was positively associated with complete hematologic remission in the chronic phase of CML [15,20]. Drug adherence has been reported as a critical factor for achieving molecular response in patients with CML [4][5][6][7], and non-adherence to TKI therapy may influence the disease outcome [5].…”

Clinical Importance of Drug Adherence during Tyrosine Kinase Inhibitor Therapy for Chronic Myelogenous Leukemia in Chronic Phase

“…After switching from IM to NILO, the total number of ADEs decreased in most cases. Although new ADEs developed initially after switching to NILO, tolerance was acquired by management of ADEs [3,16]. In particular, fluid retention, digestive symptoms, and muscle symptoms including facial edema, peripheral edema, lids edema, general fatigue, depression, nausea, muscle pain and muscle cramps induced by IM were reduced significantly (Figure 4).…”

“…These results might be due to the difference in drug adherence between the TKI groups. It has been reported that the Morisky high adherence was positively associated with complete hematologic remission in the chronic phase of CML [16,21]. Drug adherence has been reported as a critical factor for achieving molecular response in patients with CML [4][5][6][7], and non-adherence to TKI therapy may influence the disease outcome [5].…”

Inotuzumab ozogamicin in clinical development for acute lymphoblastic leukemia and non-Hodgkin lymphoma

“…The prognosis of adults with relapsed /refractory (R/R) acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) is still very poor [1][2][3][4][5]. With the increasing use of next-generation sequencing (NGS) and molecular biomarkers, early diagnosis and targeted therapy become possible [6][7][8][9][10]. It appears that NGS-based minimal residue disease (MRD) monitoring may better predict MRD relapse and lead to earlier intervention [11].…”