Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias

Cortes, Jorge; Gambacorti‐Passerini, Carlo; Kim, Dong Wook; Kantarjian, Hagop M.; Lipton, Jeff H.; Lahoti, Amit; Talpaz, Moshe; Matczak, Ewa; Barry, Elly; Leip, Eric; Brümmendorf, Tim H.; Khoury, H. Jean

doi:10.1016/j.clml.2017.06.001

Cited by 44 publications

(27 citation statements)

References 39 publications

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“…Increased blood creatinine (any grade) had a higher incidence in years 3 and 4 (5% each) versus years 1 (2%) and 2 (1%) in the CP 2L cohort and in year 4 (13%) versus years 1 (7%), 2 (4%), and 3 (3%) in the CP 3L cohort [ 5 , 9 ]. However, recently published results suggest that the decline in renal function associated with long-term bosutinib treatment is reversible and similar in frequency and characteristics to that observed with long-term imatinib [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia

2018

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Bosutinib (SKI-606) is an oral, dual Src/Abl tyrosine kinase inhibitor (TKI) approved for treatment of patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) that is resistant or intolerant to prior TKI therapy or for whom other TKIs are not appropriate choices. The objective of this review is to provide a longitudinal summary of toxicities that may arise during treatment with second-line or later bosutinib in patients with Ph+ chronic phase CML and to provide strategies for managing these toxicities. As bosutinib is not currently indicated for newly diagnosed CML, toxicities associated with first-line treatment are not reviewed. Recognition and optimal management of these toxicities can facilitate patient compliance and affect treatment outcomes.

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Section: Resultsmentioning

confidence: 99%

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia

2018

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“…Bosutinib has been associated with a decrease in glomerular filtration rate that is typically modest and potentially reversible (similar to what has been reported with imatinib). 19 , 20 Dose adjustments are recommended in patients with baseline and treatment-emergent renal impairment. 6 , 19 Careful monitoring, supportive care, and prompt management of toxicities may allow patients to continue treatment long term.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study

et al. 2018

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Bosutinib is a Src/Abl tyrosine kinase inhibitor indicated for adults with newly-diagnosed Philadelphia positive chronic myeloid leukemia or with resistant/intolerant disease. We report the final results of a phase I/II study of second-line bosutinib in chronic phase chronic myeloid leukemia patients after imatinib failure (n=284). Median follow up and treatment durations were 54.8 (range 0.6–96.3) and 25.6 (0.2–96.3) months, respectively. At years 2 and 5, 54% and 40% of patients, respectively, remained on bosutinib. Cumulative major cytogenetic response and complete cytogenetic response rates (newly-attained or maintained from baseline) were 58% and 46%, respectively, by year 2 and 60% and 50% by year 5. Kaplan-Meier probability of maintaining major and complete cytogenetic response was 76% and 78%, respectively, at year 2 and 71% and 69% at year 5. Cumulative incidence of on-treatment disease progression/death was similar at years 5 (19%) and 2 (15%); Kaplan-Meier overall survival was 91% at year 2 and 84% at year 5. Of 169 patients who had discontinued bosutinib by year 5, 38 did so after year 2, most commonly for disease progression (n=11). Most adverse events initially occurred within two years. Overall, gastrointestinal events were the most common (diarrhea 86%, nausea 46%, vomiting 37%); the most common grade 3/4 toxicity was thrombocytopenia (25%). None of the 4 on-treatment deaths in years 3–5 were related to bosutinib. Bosutinib demonstrated durable efficacy and manageable toxicity through year 5 confirming its importance in the treatment of chronic phase chronic myeloid leukemia patients resistant/intolerant to prior imatinib. This trial was registered at clinicaltrials.gov identifier: 00261846.

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“…Renal AE data has not yet been reported for the BFORE trial [6]. In an analysis of the phase 1/2 study and the BELA trial, renal AEs were reported in 52/403 patients with CP-CML (13%) receiving ≥ 2L bosutinib, and in 22/248 (9%) receiving 1L bosutinib, over a follow-up of at least 48 months [30]. The most common renal AE in both studies was increased blood creatinine (in 10% of the ≥ 2L patients and 6% of the 1L patients) [30].…”

Section: Recommendations For Managing Aes Following Treatment With Bomentioning

confidence: 99%

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

et al. 2018

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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.

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Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias

Abstract: Long-term bosutinib treatment is associated with an apparently reversible decline in renal function with frequency and characteristics similar to renal decline observed with long-term imatinib treatment. Patients with risk factors for Grade ≥ 3b eGFR should be monitored closely.

Cited by 44 publications

References 39 publications

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia

Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia

Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study

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

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