Colon Perforations in MM, While Rare, Linked With Corticosteroids

Colon perforation in patients with multiple myeloma (MM) is rare, associated with corticosteroids, and can be treated successfully with urgent surgery, according to a new study.

The report, published in the journal Cancer Medicine, offers real-world data about the circumstances of 30 patients who experienced the serious complication.

The retrospective analysis is based on patients who sought care at all 3 Mayo Clinic locations for MM and developed colonic perforation. As corresponding author Morie A. Gertz, MD, and colleagues noted, minor gastrointestinal complications are common in patients with MM, but colon perforations are not. Out of more than 5500 patients treated for MM in between 1997 and 2020, only 76 patients experienced gastrointestinal perforations, and 46 of those were excluded from the study due to factors such as colonic carcinoma or concomitant amyloid light-chain amyloidosis.

Of the 30 remaining patients, the median age was 66 years and 22 of the patients were male. The median time from MM diagnosis to perforation was 4 months.

The treatment regimens of the patients varied, but all were taking dexamethasone (ranging from 10 mg/week to 40 mg/day at cycles of 4 days on and 4 days off). Nearly half (14 patients) were treated with bortezomib at the time of perforation, 11 were treated with oxycodone prior to the perforation, and 6 patients had peripheral neuropathy prior to perforation. Four patients underwent autologous stem cell transplantation, though in all 4 cases the procedure took place more than a year before the perforation. Four patients were on high-dose dexamethasone without chemotherapy at the time of perforation.

Most of the patients (20) were on their first line of therapy at the time of perforation, and the remainder were spread out between second-line and fifth-line therapies. The median duration from the initiation of the current line of therapy to perforation was 2 months.

In terms of treatment, 25 patients needed ostomies and all survived surgery. Eighty percent of patients experienced diverticulitis. Twenty-six patients were able to resume MM treatment following surgery, and 23 patients continued dexamethasone post-surgery. The patients survived a median of 20 months following perforation.

The majority of patients (23) received high-dose steroids (which the authors designated as 40 mg or more per week), including 14 patients who received very high doses, “so we are unable to show that the perforations are related to the dose of dexamethasone.”

While they could not unequivocally exclude other reasons, the authors noted that bowel perforations have long been associated with corticosteroids. A link between corticosteroids and diverticulitis has also been previously reported.

The cause of the potential link is not known, but Gertz and colleagues wrote that steroids impair mucosal renewal, which enables bacteria to penetrate the mucosal barrier.

“Colonic diverticula are sites of high concentrations of bacteria due to stasis, which would predispose to bacterial translocation through the mucosa and submucosa,” they said. “The lack of muscularis in the diverticula makes this area more vulnerable to perforations. Steroids also impair the inflammatory response, diminishing host defenses.”

Thus, they said, it might be possible that diverticular disease sets the stage for perforation. In any case, early diagnosis is beneficial and improves patient prognosis.

“Perforations of the colon must be added to the list of adverse effects of MM treatments,” they concluded. “Because the clinical manifestations may be obscured, abdominal complaints in MM patients treated with steroids should be addressed seriously and promptly.”

Reference

Vaxman, I,Al Saleh, AS,Kumar, S, et al. Colon perforation in multiple myeloma patients–A complication of high‐dose steroid treatment. Cancer Med.2020; 00:1– 7. doi: 10.1002/cam4.3507​