Large-scale study provides real-world data on rare side effect of cancer immunotherapy

Researchers led by investigators at Mass General Brigham have published valuable information about a rare but serious complication of anti-cancer immunotherapy, providing the first large-scale description of its risk factors and clinical course, and underscoring the importance of early diagnosis and treatment. The findings are published in Blood and simultaneously presented at the American Society of Hematology Annual Meeting.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, but they can trigger autoimmune side effects. Among these immune-related adverse events, ICI-associated immune thrombocytopenia (ICI-ITP)—a condition in which platelet counts drop dangerously low—is rare and poorly understood.

“We worked with colleagues at Mass General Brigham and with collaborators from six other major academic cancer centers across the U.S. to query the records of over 86,000 patients who received ICI therapy between 2016 and 2023, ultimately identifying 214 patients—or 0.25%—who developed ICI-ITP,” said lead author Rebecca Karp Leaf, MD, a hematologist with the Mass General Brigham Cancer Institute.

The team found that patients who developed ICI-ITP tended to have lower platelet counts at the start of ICI treatment, received therapy that included multiple ICI drug classes, had stage 4 cancer, and experienced additional immune-related adverse events.

ICI-ITP occurred at a median of eight weeks after ICI initiation. Medications used to treat patients with ICI-ITP included glucocorticoids, immune globulin, and thrombopoietin receptor agonists. Recovery occurred in 161 patients (75.2%) at a median of 2.3 weeks. Of 76 patients who were started back on ICIs after being treated for ICI-ITP, 23 (30.3%) developed recurrent ICI-ITP.

“We found that nearly 70% of patients who were rechallenged with ICIs after an initial episode of ICI-ITP did not develop of this immune-related adverse event, which provides reassuring evidence that, with careful monitoring, ICI rechallenge is feasible for most patients,” said senior author David Leaf, MD, MMSc, FASN, Director of Clinical and Translational Research in Acute Kidney Injury in the Division of Renal Medicine in the Mass General Brigham Department of Medicine.

The investigators also found evidence that ICI-ITP and its severity were independently linked with a higher risk of death. Those with severe ICI-ITP had a nearly 3-fold higher risk of dying compared with those without ICI-ITP, underscoring the importance of prompt recognition and treatment.