Reduction of Imatinib Concentration After Gastric Bypass Surgery

Abstract 4948

Imatinib mesylate is an orally bioavailable inhibitor of several protein tyrosine kinases, including BCR-ABL, which was approved for BCR-ABL–positive CML. This oral agent has approximately 98% oral bioavailability independent of a meal, and it is eliminated by biliary excretion and hepatically metabolized. Better clinical outcomes have been associated with higher steady state imatinib trough levels for both CML and GIST. Because imatinib is absorbed, excreted, and possibly recycled in the gastrointestinal tract, gastrointestinal disorders impairing absorption may hinder achieving therapeutically effective imatinib levels. We present the case of a woman with CML who underwent biliopancreatic diversion with duodenal switch for weight loss leading to a marked reduction in imatinib concentration, and as a consequence, inadequate suppression of her CML. This is a 54 year old obese African American woman who achieved complete hematological remission (CHR), and complete cytogenetics remission (CCyR) and good molecule response with a BCR-ABL/c-ABL ratio of 0.015 (1.5%) with close to therapeutic imatinib trough level at 965 ng/mL prior to gastric bypass surgery on imatinib 400mg daily. The patient underwent laparoscopic biliopancreatic diversion with duodenal switch, concomitant cholecystectomy, and appendectomy. Her adjusted imatinib steady state trough level declined to 166ng/mL, 17% of the pre-surgery level and below the concentration required to suppress BCR-ABL activity leading to a 0.5 log increase in BCR-ABL/c-ABL ratio of 0.083 (8.3%). Escalation of imatinib to 400 mg BID led to imatinib trough level of 734 ng/mL and decrease of BCR-ABL/c-ABL ratio to 0.024 (2.4%), a value comparable to the ratio achieved while on imatinib 400mg daily prior to the gastric bypass surgery. Eventually, our patient lost almost 50kg (close to 45% of her original weight) within a year period. Interestingly, the imatinib level increased to 2124 ng/mL on imatinib 400mg twice a day after the substantial weight loss, supporting the correlation of imatinib level and actual body weight. Her PCR BCR-ABL/c-ABL from peripheral blood still revealed a ratio of 0.072 (7.2%) with high therapeutic imatinib level, and a secondary generation TKI, nilotinib, was initiated at 400mg twice a day. The detail of the clinical course was listed in table below.

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