IMMUNE RELATED PROBLEMS WITH IPILIMUMAB 

NEW YORK (Reuters Health) Feb 12 - Immune-related adverse events associated with ipilimumab emerge within months after treatment starts and usually resolve when treatment stops, researchers report.

"Ipilimumab is a well-tolerated drug if managed properly," Dr. Jeffrey S. Weber from the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida told Reuters Health. "Good communication and vigilance about side effects is the key to appropriate management of the toxicities of this drug."

In a paper online February 7th in Cancer, Dr. Weber and colleagues presented data from the phase III MDX010-20 study, with a special focus on patterns of development and resolution of immune-related adverse events.

Overall, 676 patients with melanoma received either ipilimumab + gp100 peptide vaccine (403 patients), ipilimumab alone (137 patients), or gp100 alone (136 patients).

Treatment-related adverse events occurred in 105 ipilimumab monotherapy patients (77%); 80 of them (76%) reported an immune-related adverse event.

Grade 3 or 4 events occurred in 10% to 15% of ipilimumab-treated patients. Fourteen patients (2.6%) died of causes related to study drugs; seven deaths were associated with immune-related adverse events.

The most commonly reported immune-related adverse events affected the skin (41%) and GI tract (31%). About 5% of ipilimumab patients developed endocrine disorders.

Most immune-related adverse events developed within 12 weeks of initial dosing and their median time to resolution was six to eight weeks. Fewer than 10% of patients receiving any ipilimumab treatment reported developing an immune-related adverse event more than 70 days after their last dose of study drug, and all of these were grade 1 or 2 in severity.

Most immune-related adverse events, including grade 3/4 events, were successfully managed with careful monitoring and early treatment with corticosteroids. Only five patients needed infliximab to manage the GI immune-related adverse events, and all five showed some improvement after that intervention.

All but two patients whose deaths were attributed to ipilimumab treatment had severe GI events, most commonly colitis, and at least two of these did not receive steroid treatment until three weeks after the onset of symptoms.

"Diarrhea and abdominal discomfort which might be symptoms of colitis, are the leading concerns with the use of ipilimumab, closely followed by fatigue and other non-specific complaints of malaise that might be symptoms of hypophysisitis," Dr. Weber said.

Dr. Weber said that "persistent grade 2 side effects at one to two weeks without resolution and onset of grade 3 side effects felt to be drug related" should prompt corticosteroid therapy.

"Education of the patient in term of when to call, and what side effects to look for, and training of the medical staff, particularly the nursing and mid-level practitioners that are an integral part of every oncologist's office, are key elements in the successful administration of this drug," Dr. Weber concluded.

SOURCE: http://bit.ly/WH2Ido

Cancer 2013.