Gastrointestinal perforation in light chain amyloidosis in the era of novel agent therapy – a case series and review of the literature

Abstract

Gastrointestinal (GI) perforation is remarkably rare in patients with light chain (AL) amyloidosis and has not yet been reported in patients with AL amyloidosis treated with novel agents. Only 24 cases of GI perforation have previously been reported in the setting of AL amyloidosis of which 15 had available information in English. All 15 did not receive novel agent therapy and six died early after experiencing GI perforation. This study reports the characteristics and outcome of AL patients that developed GI perforation in the era of novel agent treatment. Seven patients were reviewed. In two patients, GI perforation was the presenting symptom of AL amyloidosis, whereas five patients developed GI perforations following initiation of an anti-AL therapy (three after bortezomib-based, 1 after lenalidomide-based and 1 after thalidomide-based therapy). All patients underwent surgery and survived the perforation. Treatment was renewed following surgery in six of seven patients, with no further GI complications. In conclusion, GI perforation in AL amyloidosis is rare and mostly reported after treatment initiation. Urgent surgery appears to be lifesaving and renewal of the anti-AL novel therapy appears to be safe, with no significant risk for re-perforation or GI toxicity. Prognosis in these patients is related to severity of the disease and response to therapy rather than the development of GI perforation.

Colon perforation in multiple myeloma patients – A complication of high‐dose steroid treatment

“…In MM, high‐dose dexamethasone is a fundamental part of all treatment regimens. For MM patients with perforated colon, some clinicians postulate that bortezomib is the culprit, 20 but we believe, although cannot prove, that although bortezomib and immunomodulatory agents can cause neuropathies 35,36 and influence bowel motility, 6 steroids are the cause of the perforation. Fourteen patients (46%) received very high doses of steroids (dexamethasone 40 mg day 1–4, 9–12, 17–20 q 28 days) and 23 patents (77%) received high‐dose steroids (defined as a dose higher than 40 mg/week) so we are unable to show that the perforations are related to the dose of dexamethasone.…”

“…A case series reported seven patients with bowel perforations, all of them were treated with dexamethasone as part of their treatment regimen prior to perforation. One had diverticulitis and all had amyloid deposition in their pathological specimen 20 . In this cohort, treatment was resumed in four patients without further GI complications.…”

“…One had diverticulitis and all had amyloid deposition in their pathological specimen. 20 In this cohort, treatment was resumed in four patients without further GI complications.…”

“…In AL amyloidosis, intestinal involvement is present in 15% of the patients 19 and gastrointestinal perforations have previously been reported. 20 A case series reported seven patients with bowel perforations, all of them were treated with dexamethasone as part of their treatment regimen prior to perforation. One had diverticulitis and all had amyloid deposition in their pathological specimen.…”

Gastric perforation caused by secondary systemic amyloidosis

“…Gastrointestinal perforation is a rare occasion in systemic amyloidosis. 29,30 Ganzoni and Schneider 31 described a case of gastric perforation due to primary amyloidosis in 1981. To the best of our knowledge, this is the second case of gastric perforation caused by systemic amyloidosis.…”