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Complications associated with immunotherapy for brain metastases.

ABSTRACT: PURPOSE OF REVIEW:Median survival after the diagnosis of brain metastases has historically been on the order of months. With the recent development of immune checkpoint inhibitors, intracranial activity and durable responses have been observed in brain metastases on multiple phase 2 clinical trials, which have primarily been conducted in patients with melanoma. Immune-related adverse events related to checkpoint inhibitor therapy of brain metastasis can present unique challenges for the clinician and underscore the need for a multidisciplinary team in the care of these patients. The goal of this review is to address the current knowledge, limitations of understanding, and future directions in research regarding immune therapy trials and neurologic toxicities based on retrospective, prospective, and case studies. RECENT FINDINGS:Immune therapy has the potential to exacerbate symptomatic edema and increase the risk of radiation necrosis in previously irradiated lesions. Neurologic toxicities will likely increase in prevalence as more patients with brain metastatic disease are eligible for immune therapy. SUMMARY:An improved understanding and heightened awareness of the unique neurologic toxicities that impact this patient group is vital for mitigating treatment-related morbidity and mortality.

SUBMITTER: Tran TT

PROVIDER: S-EPMC7398556 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Complications associated with immunotherapy for brain metastases.

Tran Thuy T TT Jilaveanu Lucia B LB Omuro Antonio A Chiang Veronica L VL Huttner Anita A Kluger Harriet M HM

Current opinion in neurology 20191201 6

<h4>Purpose of review</h4>Median survival after the diagnosis of brain metastases has historically been on the order of months. With the recent development of immune checkpoint inhibitors, intracranial activity and durable responses have been observed in brain metastases on multiple phase 2 clinical trials, which have primarily been conducted in patients with melanoma. Immune-related adverse events related to checkpoint inhibitor therapy of brain metastasis can present unique challenges for the ...[more]

PMID: 31577604

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Project description:Immunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic radiosurgery (SRS) and immunotherapy or postoperative SRS alone. We hypothesize that postoperative SRS and immunotherapy will result in a lower rate of LMD with acceptable toxicity compared with postoperative SRS. One hundred and twenty-nine patients with non-small-cell lung cancer (NSCLC) and melanoma BM who received postoperative fractionated SRS (fSRS; 3×9 Gy) in combination with immunotherapy or postoperative fSRS alone for completely resected BM were retrospectively evaluated. The primary endpoint of the study was the rate of LMD after treatments. The secondary endpoints were local failure, distant brain parenchymal failure (DBF), overall survival (OS), and treatment-related toxicity. Sixty-three patients received postoperative SRS and immunotherapy, either nivolumab or pembrolizumab, and 66 patients received postoperative SRS alone to the resection cavity. With a median follow-up of 15 months, LMD occurred in 19 patients: fSRS group, 14; fSRS and immunotherapy, 5. The 12-month LMD cumulative rates were 22% (95% CI 14% to 37%) in the fSRS group and 6% (95% CI 2% to 17%) in the combined treatment group (p=0.007). Resection cavity control was similar between the groups, whereas DBF and OS were significantly different; the 1-year DBF rates were 31% (95% CI 20% to 46%) in the fSRS and immunotherapy group and 52% (95% CI 39% to 68%) in the fSRS group; respective OS rates were 78% (95% CI 67% to 88%) and 58.7% (95% CI 47% to 70%). Twenty-two patients undergoing postoperative fSRS and immunotherapy and nine subjected to postoperative fSRS experienced treatment-related imaging changes suggestive of radiation-induced brain necrosis (p=0.02). Postoperative fSRS in combination with immunotherapy decreases the incidence of LMD and DBF in patients with resected BM from NSCLC and melanoma as compared with fSRS alone, reducing the rate of neurological death and prolonging survival.

Dataset Information

Complications associated with immunotherapy for brain metastases.

Publications

Complications associated with immunotherapy for brain metastases.

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