Martina Imbimbo

BACKGROUND: Steroids are frequently used in patients with metastatic non-small cell lung cancer (mNSCLC), but they could be detrimental for patients treated with immune checkpoint inhibitors (ICIs). Here, we assessed the association between early use of steroids, clinical outcomes and peripheral immune blood cells modulation in patients with mNSCLC treated with ICIs. METHODS: We reviewed patients with mNSCLC treated at our institution between April 2013 and December 2017. Early use of steroids was defined as the use of a daily prednisone-equivalent dose ≥10 mg for at least 1 day within 28 days after ICI initiation. Peripheral immune blood cell counts were retrieved at baseline and at 4 and 6 weeks after ICI initiation. RESULTS: Out of 151 patients included, 35 (23%) made early use of steroids that was associated with poor disease control (OR 0.32, p=0.006), progression-free survival (HR 1.80, p=0.003) and overall survival (HR 2.60, p<0.001). Early use of steroids significantly correlated with higher median absolute neutrophil count, neutrophil to lymphocyte ratio (NLR) and derived NLR, and lower median absolute and relative eosinophil count, both at 4 and 6 weeks after ICI initiation. CONCLUSIONS: In patients with mNSCLC treated with ICIs, early use of steroids was associated with worse clinical outcomes and remarkable modulation of peripheral blood immune cells, which could contribute to restraining the activation of antitumour immunity. If confirmed in prospective studies, these findings would highlight the importance of carefully evaluating and, whenever possible, avoiding steroids during early phases of ICI treatment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy but frequently cause immune-related adverse events (irAEs). Description of late-onset and duration of irAEs in the literature is often incomplete. METHODS: To investigate reporting and incidence of late-onset and long-lasting irAEs, we reviewed all registration trials leading to ICI's approval by the US FDA and/or EMA up to December 2019. We analysed real-world data from all lung cancer (LC) and melanoma (Mel) patients treated with approved ICIs at the University Hospital of Lausanne (CHUV) from 2011 to 2019. To account for the immortal time bias, we used a time-dependent analysis to assess the potential association between irAEs and overall survival (OS). RESULTS: Duration of irAEs and proportion of patients with ongoing toxicities at data cut-off were not specified in 56/62 (90%) publications of ICIs registration trials. In our real-world analysis, including 437 patients (217 LC, 220 Mel), 229 (52.4%) experienced at least one grade ≥2 toxicity, for a total of 318 reported irAEs, of which 112 (35.2%) were long-lasting (≥6 months) and about 40% were ongoing at a median follow-up of 369 days [194-695] or patient death. The cumulative probability of irAE onset from treatment initiation was 42.8%, 51.0% and 57.3% at 6, 12 and 24 months, respectively. The rate of ongoing toxicity from the time of first toxicity onset was 42.8%, 38.4% and 35.7% at 6, 12 and 24 months. Time-dependent analysis showed no significant association between the incidence of irAEs and OS in both cohorts (log Rank p = 0.67 and 0.19 for LC and Mel, respectively). CONCLUSIONS: Late-onset and long-lasting irAEs are underreported but common events during ICIs therapy. Time-dependent survival analysis is advocated to assess their impact on OS. Real-world evidence is warranted to fully capture and characterise late-onset and long-lasting irAEs in order to implement appropriate strategies for patient surveillance and follow-up.

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies. Despite surgery and chemotherapy, 5-years survival rates have improved only modestly over the past few decades remaining at 45% for advanced stages. Therefore, novel therapies are urgently needed. The presence of tumor-infiltrating lymphocytes (TILs) in OC tumor microenvironment (TME) has already proved to be correlated with overall survival (OS), while immune evasion mechanisms are associated with poor prognosis. Although these data indicate that immunotherapy has a strong rationale in OC, single agent immune-checkpoints inhibitors (ICIs) have shown only modest results in this malignancy. In this review, we will discuss immune-targeting combination therapies and adoptive cell therapy (ACT), highlighting the challenges represented by these strategies, which aim at disrupting the stroma-tumor barrier to boost immune system against ovarian cancer.