Stage 4 lung adenocarcinoma with RET fusion responding to pralsetinib

What happened, in summary

This 60-year-old man was diagnosed with lung adenocarcinoma in April 2019. He underwent right upper lobectomy with visible pleural nodule resection on April 26, 2019, and pathology confirmed adenocarcinoma with malignant pleural dissemination. The postoperative stage was pT2aN1M1a, Stage IVA. Next-generation sequencing identified a KIF5B-RET fusion, making RET-targeted treatment relevant later in his course. His first 3 systemic treatment lines were pemetrexed plus cisplatin plus pembrolizumab, then paclitaxel plus carboplatin plus bevacizumab, then anlotinib. These were stopped because of progression or intolerance. On February 10, 2022, he started pralsetinib 400 mg daily as fourth-line therapy and developed grade 2 neutropenia. About 2.5 months later, he was hospitalized with fever and then severe dyspnea. CT showed widespread ground-glass opacities with many cystic lesions in both lungs and right lower-lung consolidations. Pralsetinib was held, and several empiric anti-infective treatments were tried. His oxygen saturation worsened, and bronchoalveolar lavage testing confirmed Pneumocystis jirovecii pneumonia with a high sequence count. He was treated with trimethoprim/sulfamethoxazole, caspofungin, and clindamycin, then continued oral TMP-SMZ after early discharge. The infection was classified as grade 3 PJP. During this episode, CT also showed reduced metastatic lesion size, consistent with partial response to pralsetinib. After clinical recovery, he restarted pralsetinib because treatment options were limited and the drug was controlling the cancer. Three-month follow-up CT showed disappearance of the lung infection changes and further decrease in metastatic disease. As of March 2025, after 13 months of continued pralsetinib, there was no progressive disease and no recurrence of the adverse event.