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Gastrointestinal Stromal Tumor Arising From the Small Intestine in a Heart Transplant Recipient on Hemodialysis and Chronic Immunosuppression: A Case Report
Background
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors with worse prognosis if arising from the small bowel. Surgery remains the mainstay of treatment for patients with resectable tumors. Imatinib has become the standard treatment in cKIT-positive GISTs with significant morbidity in neoadjuvant, adjuvant, and palliative settings. There are limited data on efficacy and safety of imatinib in dialysis patients, and chemotherapy dosing is challenging in dialysis patients with multiple comorbidities.
Presentation
A 68-year-old male with a history of orthotopic heart transplantation on sirolimus with prednisone, cardiac allograft vasculopathy, plus ESRD on peritoneal dialysis (PD), presented with lower abdominal pain and fever. Abdominal imaging revealed a right lower quadrant (RLQ) mass with concern for bowel perforation.
Diagnosis and Treatment
The patient underwent exploratory laparoscopy with small bowel resection, excision of the mesenteric small bowel mass, drainage and washout of intraabdominal abscess, removal of PD catheter, and transition to hemodialysis. Pathology revealed a 14.5-cm high-grade GIST with mixed spindle and epithelioid types involving the ileal wall and mesentery, consistent with pT4 primary tumor and stage IIIB disease. Molecular testing was positive for c-KIT and DOG-1 mutations.
After a prolonged recovery, repeat abdominal imaging demonstrated metastatic liver disease and a new RLQ lesion. The patient was started on palliative imatinib 100 mg daily with subsequent increase to 200 mg daily. He was monitored closely for toxicities but reported only mild nausea controlled with ondansetron. Hemodialysis was continued 3 times per week. Follow up scans 3 months later showed improvement in RLQ mass and hepatic lesions. The patient remains on the current dose 15 months after the diagnosis.
Conclusion
To our knowledge, this is the first case of a small intestinal GIST in a heart transplant recipient treated with dose-reduced imatinib with concurrent dialysis and immunosuppression. Treatment decision-making was complex given concern for cardiotoxicity with pre-existing cardiac disease and drug-drug interactions with immunosuppressive agents. While some literature suggests standard dose imatinib with dialysis, no large-scale studies evaluated pharmacokinetics of imatinib with creatinine clearance < 20 mL/min. There is a need for further studies to determine dosing strategies for such patients.
Background
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors with worse prognosis if arising from the small bowel. Surgery remains the mainstay of treatment for patients with resectable tumors. Imatinib has become the standard treatment in cKIT-positive GISTs with significant morbidity in neoadjuvant, adjuvant, and palliative settings. There are limited data on efficacy and safety of imatinib in dialysis patients, and chemotherapy dosing is challenging in dialysis patients with multiple comorbidities.
Presentation
A 68-year-old male with a history of orthotopic heart transplantation on sirolimus with prednisone, cardiac allograft vasculopathy, plus ESRD on peritoneal dialysis (PD), presented with lower abdominal pain and fever. Abdominal imaging revealed a right lower quadrant (RLQ) mass with concern for bowel perforation.
Diagnosis and Treatment
The patient underwent exploratory laparoscopy with small bowel resection, excision of the mesenteric small bowel mass, drainage and washout of intraabdominal abscess, removal of PD catheter, and transition to hemodialysis. Pathology revealed a 14.5-cm high-grade GIST with mixed spindle and epithelioid types involving the ileal wall and mesentery, consistent with pT4 primary tumor and stage IIIB disease. Molecular testing was positive for c-KIT and DOG-1 mutations.
After a prolonged recovery, repeat abdominal imaging demonstrated metastatic liver disease and a new RLQ lesion. The patient was started on palliative imatinib 100 mg daily with subsequent increase to 200 mg daily. He was monitored closely for toxicities but reported only mild nausea controlled with ondansetron. Hemodialysis was continued 3 times per week. Follow up scans 3 months later showed improvement in RLQ mass and hepatic lesions. The patient remains on the current dose 15 months after the diagnosis.
Conclusion
To our knowledge, this is the first case of a small intestinal GIST in a heart transplant recipient treated with dose-reduced imatinib with concurrent dialysis and immunosuppression. Treatment decision-making was complex given concern for cardiotoxicity with pre-existing cardiac disease and drug-drug interactions with immunosuppressive agents. While some literature suggests standard dose imatinib with dialysis, no large-scale studies evaluated pharmacokinetics of imatinib with creatinine clearance < 20 mL/min. There is a need for further studies to determine dosing strategies for such patients.
Background
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors with worse prognosis if arising from the small bowel. Surgery remains the mainstay of treatment for patients with resectable tumors. Imatinib has become the standard treatment in cKIT-positive GISTs with significant morbidity in neoadjuvant, adjuvant, and palliative settings. There are limited data on efficacy and safety of imatinib in dialysis patients, and chemotherapy dosing is challenging in dialysis patients with multiple comorbidities.
Presentation
A 68-year-old male with a history of orthotopic heart transplantation on sirolimus with prednisone, cardiac allograft vasculopathy, plus ESRD on peritoneal dialysis (PD), presented with lower abdominal pain and fever. Abdominal imaging revealed a right lower quadrant (RLQ) mass with concern for bowel perforation.
Diagnosis and Treatment
The patient underwent exploratory laparoscopy with small bowel resection, excision of the mesenteric small bowel mass, drainage and washout of intraabdominal abscess, removal of PD catheter, and transition to hemodialysis. Pathology revealed a 14.5-cm high-grade GIST with mixed spindle and epithelioid types involving the ileal wall and mesentery, consistent with pT4 primary tumor and stage IIIB disease. Molecular testing was positive for c-KIT and DOG-1 mutations.
After a prolonged recovery, repeat abdominal imaging demonstrated metastatic liver disease and a new RLQ lesion. The patient was started on palliative imatinib 100 mg daily with subsequent increase to 200 mg daily. He was monitored closely for toxicities but reported only mild nausea controlled with ondansetron. Hemodialysis was continued 3 times per week. Follow up scans 3 months later showed improvement in RLQ mass and hepatic lesions. The patient remains on the current dose 15 months after the diagnosis.
Conclusion
To our knowledge, this is the first case of a small intestinal GIST in a heart transplant recipient treated with dose-reduced imatinib with concurrent dialysis and immunosuppression. Treatment decision-making was complex given concern for cardiotoxicity with pre-existing cardiac disease and drug-drug interactions with immunosuppressive agents. While some literature suggests standard dose imatinib with dialysis, no large-scale studies evaluated pharmacokinetics of imatinib with creatinine clearance < 20 mL/min. There is a need for further studies to determine dosing strategies for such patients.
In-Depth Look at a Community- Based Population of Multiple Myeloma (MM) Patients Undergoing an in-Class Transition (iCT) from Parenteral Bortezomib to Oral Ixazomib in the United States (US) MM-6 Study
BACKGROUND: Randomized clinical trials (RCTs) typically enroll highly selected populations. Oncology RCTs have an average of 16 eligibility criteria (Unger JNCI 2014). Registry analyses indicate that up to ~40% of ‘real-world’ MM patients are ineligible for RCTs based on common criteria (Shah CLML 2017).
PURPOSE: US MM-6 (NCT03173092) is evaluating iCT from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) in MM patients treated at US community oncology centers. Eligibility criteria are less stringent than RCTs, to enroll patients more representative of the real-world MM population.
METHODS: Non-transplant-eligible newly-diagnosed MM patients with stable disease or better after 3 cycles of bortezomib-based induction are being enrolled at 22 US community sites (including three Veterans Affairs hospitals) to receive ixazomib-Rd for up to 39 28- day cycles or until progression/toxicity.
DATA ANALYSIS: We reviewed 84 consecutively enrolled patients using standard RCT eligibility criteria. Initially, six criteria were explored to determine the proportion of patients who might have been RCT-ineligible: renal dysfunction, congestive heart failure (CHF), stroke, prior malignancies, chronic obstructive pulmonary disease (COPD), and memory loss. Dosing information was evaluated to determine any correlation between dose modifications and eligibility status.
RESULTS: Based on six criteria, 24/84 patients (29%) may have been RCT-ineligible: 12% (n=10) had renal dysfunction, 7% (n=6) CHF, 6% (n=5) stroke, 5% (n=4) each other prior malignancies and COPD, and 2% (n=2) memory loss; 6% (n=5) had >1 criterion. Among the 24 RCT-ineligible patients, 75% (n=18), 42% (n=10), and 54% (n=13) received the highest starting doses of ixazomib (4mg), lenalidomide (25mg), and dexamethasone (40mg), respectively. Ixazomib, lenalidomide, and dexamethasone dose reductions were required in 29% (n=7), 25% (n=6), and 21% (n=5), respectively (due to adverse events [AEs]: 21% [n=5], 21% [n=5], 4% [n=1]). 50% (n=12) discontinued treatment (consent withdrawal/patient decision, n=7; disease progression, n=2; sufficient response, AE, death, each n=1); n=3/2/2 discontinued ixazomib/lenalidomide/ dexamethasone due to AEs.
IMPLICATIONS: US MM-6 is enrolling real-world, community- based MM patients, including those who may be ineligible for RCTs based on standard inclusion criteria. Our analysis indicates that iCT to ixazomib- Rd appears to be feasible in these RCT-ineligible US MM-6 patients. Further criteria will be analyzed and presented.
BACKGROUND: Randomized clinical trials (RCTs) typically enroll highly selected populations. Oncology RCTs have an average of 16 eligibility criteria (Unger JNCI 2014). Registry analyses indicate that up to ~40% of ‘real-world’ MM patients are ineligible for RCTs based on common criteria (Shah CLML 2017).
PURPOSE: US MM-6 (NCT03173092) is evaluating iCT from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) in MM patients treated at US community oncology centers. Eligibility criteria are less stringent than RCTs, to enroll patients more representative of the real-world MM population.
METHODS: Non-transplant-eligible newly-diagnosed MM patients with stable disease or better after 3 cycles of bortezomib-based induction are being enrolled at 22 US community sites (including three Veterans Affairs hospitals) to receive ixazomib-Rd for up to 39 28- day cycles or until progression/toxicity.
DATA ANALYSIS: We reviewed 84 consecutively enrolled patients using standard RCT eligibility criteria. Initially, six criteria were explored to determine the proportion of patients who might have been RCT-ineligible: renal dysfunction, congestive heart failure (CHF), stroke, prior malignancies, chronic obstructive pulmonary disease (COPD), and memory loss. Dosing information was evaluated to determine any correlation between dose modifications and eligibility status.
RESULTS: Based on six criteria, 24/84 patients (29%) may have been RCT-ineligible: 12% (n=10) had renal dysfunction, 7% (n=6) CHF, 6% (n=5) stroke, 5% (n=4) each other prior malignancies and COPD, and 2% (n=2) memory loss; 6% (n=5) had >1 criterion. Among the 24 RCT-ineligible patients, 75% (n=18), 42% (n=10), and 54% (n=13) received the highest starting doses of ixazomib (4mg), lenalidomide (25mg), and dexamethasone (40mg), respectively. Ixazomib, lenalidomide, and dexamethasone dose reductions were required in 29% (n=7), 25% (n=6), and 21% (n=5), respectively (due to adverse events [AEs]: 21% [n=5], 21% [n=5], 4% [n=1]). 50% (n=12) discontinued treatment (consent withdrawal/patient decision, n=7; disease progression, n=2; sufficient response, AE, death, each n=1); n=3/2/2 discontinued ixazomib/lenalidomide/ dexamethasone due to AEs.
IMPLICATIONS: US MM-6 is enrolling real-world, community- based MM patients, including those who may be ineligible for RCTs based on standard inclusion criteria. Our analysis indicates that iCT to ixazomib- Rd appears to be feasible in these RCT-ineligible US MM-6 patients. Further criteria will be analyzed and presented.
BACKGROUND: Randomized clinical trials (RCTs) typically enroll highly selected populations. Oncology RCTs have an average of 16 eligibility criteria (Unger JNCI 2014). Registry analyses indicate that up to ~40% of ‘real-world’ MM patients are ineligible for RCTs based on common criteria (Shah CLML 2017).
PURPOSE: US MM-6 (NCT03173092) is evaluating iCT from parenteral bortezomib-based induction to all-oral ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) in MM patients treated at US community oncology centers. Eligibility criteria are less stringent than RCTs, to enroll patients more representative of the real-world MM population.
METHODS: Non-transplant-eligible newly-diagnosed MM patients with stable disease or better after 3 cycles of bortezomib-based induction are being enrolled at 22 US community sites (including three Veterans Affairs hospitals) to receive ixazomib-Rd for up to 39 28- day cycles or until progression/toxicity.
DATA ANALYSIS: We reviewed 84 consecutively enrolled patients using standard RCT eligibility criteria. Initially, six criteria were explored to determine the proportion of patients who might have been RCT-ineligible: renal dysfunction, congestive heart failure (CHF), stroke, prior malignancies, chronic obstructive pulmonary disease (COPD), and memory loss. Dosing information was evaluated to determine any correlation between dose modifications and eligibility status.
RESULTS: Based on six criteria, 24/84 patients (29%) may have been RCT-ineligible: 12% (n=10) had renal dysfunction, 7% (n=6) CHF, 6% (n=5) stroke, 5% (n=4) each other prior malignancies and COPD, and 2% (n=2) memory loss; 6% (n=5) had >1 criterion. Among the 24 RCT-ineligible patients, 75% (n=18), 42% (n=10), and 54% (n=13) received the highest starting doses of ixazomib (4mg), lenalidomide (25mg), and dexamethasone (40mg), respectively. Ixazomib, lenalidomide, and dexamethasone dose reductions were required in 29% (n=7), 25% (n=6), and 21% (n=5), respectively (due to adverse events [AEs]: 21% [n=5], 21% [n=5], 4% [n=1]). 50% (n=12) discontinued treatment (consent withdrawal/patient decision, n=7; disease progression, n=2; sufficient response, AE, death, each n=1); n=3/2/2 discontinued ixazomib/lenalidomide/ dexamethasone due to AEs.
IMPLICATIONS: US MM-6 is enrolling real-world, community- based MM patients, including those who may be ineligible for RCTs based on standard inclusion criteria. Our analysis indicates that iCT to ixazomib- Rd appears to be feasible in these RCT-ineligible US MM-6 patients. Further criteria will be analyzed and presented.