Melanoma and Radioimmunotherapy
Immune checkpoint blockade immunotherapy is rapidly changing the standard of care for advanced melanoma and lung cancer. The PD-1/PD-L1 and CTLA-4 immune checkpoint pathways protect against autoimmune disease, ensuring that immune cells do not attack “self” cells or tissues, but tumors can sometimes co-opt these signaling pathways to evade immune attack. Immune checkpoint blockade disrupts this evasion technique to facilitate T-cell-mediated antitumor immunity. These immunotherapeutic agents were pioneered in the treatment of melanoma.3,4,6,7
Authors of a recent systematic review of 16 clinical trials reporting abscopal effects among a total of 451 patients who underwent both ipilimumab CLTA-4-targeting immune checkpoint blockade and radiotherapy for metastatic melanoma reported increased abscopal response rates and improved overall survival without increased toxicities.4 They called for prospective randomized, controlled clinical trials to confirm the link.4 The median reported abscopal effect was 26.5% and toxicity rates for grade 3 or higher adverse events ranged from 10% to 20% (median 18%) in both study treatment and control groups.4 The most frequent toxicities associated with ipilimumab monotherapy and radioimmunotherapy alike were immune-mediated colitis, skin and mucosal toxicity, and diarrhea.4
A retrospective database records review at the Washington University School of Medicine similarly found improved overall survival among patients with metastatic melanoma brain tumors who had undergone immunotherapy plus stereotactic brain radiosurgery (median 11.1 months vs 6.2 months for patients undergoing radiosurgery without immunotherapy).6
The same research team separately reported that among patients treated for extracranial metastatic melanoma, those receiving radiotherapy in addition to immunotherapy experienced significantly shorter overall survival (median OS 15.4 vs 19.4; P =.02).7 However, this was very likely an artifact caused by the inclusion of patients with bone metastases in the radiotherapy group; in a subsequent multivariate analysis, only patients undergoing bone radiotherapy experienced worse outcomes.7
The timing and sequencing of radiotherapy and immunotherapy also mattered, the study suggested. Patients who received radiotherapy at least 30 days prior to immunotherapy for soft-tissue melanoma metastases experienced longer overall survival times than those treated within 30 days of immunotherapy initiation or postimmunotherapy radiotherapy (26.1 vs 16.0 vs 15.4 months; P <.01).7
“The site and timing of radiotherapy may have important interaction with immunotherapy and need to be carefully considered in future clinical trials,” the authors cautioned.7
Bryant Furlow is a medical reporter based in Albuquerque, New Mexico.
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