Francesco Pesola

In patients with advanced non-small cell lung cancer (NSCLC), MET exon 14 ( MET ex14) skipping mutations are rare and are associated with a poor prognosis. Capmatinib, a selective oral MET inhibitor, was recently approved for the treatment of advanced MET ex14 skipping NSCLC. However, data from real-world experiences are limited. This was a retrospective analysis using real-world data from Italian patients with advanced MET ex14 skipping NSCLC who had received at least one treatment with immunotherapy and/or platinum-based chemotherapy and received compassionate use treatment with capmatinib. Patient characteristics, treatment details, discontinuations, and adverse events are reported. Overall, 53 patients received capmatinib after receiving treatment with immunotherapy and/or platinum-based chemotherapy in Italy. Patients had a median age of 74 years, mostly metastatic disease (92.5% of patients), and previously received one (66.0%) or more (2: 28.3%; 3: 5.7%) lines of standard treatment (immunotherapy and/or platinum-based chemotherapy). Most patients (98.1%) started treatment with capmatinib at the full recommended dose of 400 mg twice daily and 77.4% did not require a dose reduction. Twenty-four patients (45.3%) discontinued treatment; the most frequent reason for discontinuing treatment was disease progression, with a median estimated time to treatment discontinuation of 15.2 months. This real-world retrospective analysis confirms that capmatinib is a valuable treatment option for difficult-to-treat MET ex14 skipping NSCLC, in agreement with the data from the registration trial.

Background: Immune-checkpoint inhibitors (ICIs) as second-line therapy showed an overall survival (OS) benefit, but only 18-20% of aNSCLC patients respond with a median progression-free survival (mPFS) of 2-4 months. The identification of biomarkers to select patients most likely to benefit from ICIs is still an unmet need in clinical practice.

Background: Second-line immunotherapy showed an overall survival (OS) benefit, but only a low percentage of aNSCLC patients (pts) respond to therapy. The identification of new biomarkers to select patients for immunotherapy (IO) is a crucial topic. In our study we aim to investigate the role of peripheral blood biomarkers (PBBs) that can predict response and outcome in aNSCLC pts treated with IO.

SUMMARY: Hepatitis C virus (HCV) infection has been detected in a large proportion of patients with mixed cryoglobulinaemia (MC). Circulating ‘free’ non-enveloped HCV core protein has been demonstrated in HCV-infected patients, and this suggests its possible involvement in the formation of cryoprecipitable immune complexes (ICs). Thirty-two anti-HCV, HCV RNA-positive patients with type II MC were evaluated. Non-enveloped HCV core protein, HCV RNA sequences, total IgM, rheumatoid factor (RF) activity, IgG and IgG subclasses, C3 and C4 fractions, C1q protein and C1q binding activity were assessed in both cryoprecipitates and supernatants. Non-enveloped HCV core protein was demonstrated in 30 of 32 (93·7%) type II MC patients. After separation of cold-precipitable material, the protein was removed completely from supernatant in 12 patients (40%), whereas it was enriched in the cryoprecipitates of the remaining 18. In addition, HCV RNA and IgM molecules with RF activity were concentrated selectively in the cryoprecipitates. Differential precipitation was found for both total IgG and IgG subclasses, as they were less represented in the cryoglobulins and no selective enrichment was noted. Immunological characterization of HCV core protein-containing cryoprecipitating ICs after chromatographic fractionation showed that the IgM monoclonal component had RF activity, whereas anti-HCV core reactivity was confined to the IgG fraction. C1q enrichment in addition to high avidity of ICs for C1q binding in the cryoprecipitates suggest that complement activation may occur through the C1q protein pathway. The present data demonstrate that non-enveloped HCV core protein is a constitutive component of cryoprecipitable ICs in type II MC patients.