Clinical Trials of Cellular Therapies in Solid Tumors.

In the past years cancer treatments have drastically changed, mainly due to the development of immune checkpoint inhibitors capable of immune modulation in vivo, thus providing major clinical benefit in a number of malignancies. Simultaneously, considerable technical refinements have opened new prospects for the development of immune cell-based medicinal products and unprecedented success with chimeric antigen receptor (CAR)-T cells targeting B-cell hematologic malignancies has been obtained. However, T cell therapies introduced and performed in the field of solid tumors have produced so far only limited responses in selected patient populations. This standstill is attributable to the difficulty in identifying target antigens which are homogeneously expressed by all tumor cells while absent from normal tissues, and the limited T cell persistence and proliferation in a hostile tumor microenvironment that favors immune escape. Replicating the results observed in hematology is a major scientific challenge in solid tumors, and ongoing translational and clinical research is focused on obtaining insight into the mechanisms of tumor recognition and evasion, and how to improve the efficacy of cellular therapies, also combining them with immune checkpoint inhibitors or other agents targeting either the cancer cell or the tumor environment. This paper provides an overview of current adaptive T cell therapy approaches in solid tumors, the research performed to increase their efficacy and safety, and results from ongoing clinical trials.

The Role of Pre-treatment Inflammatory Biomarkers in the Prediction of an Early Response to Panitumumab in Metastatic Colorectal Cancer.

Background Systemic inflammation is a critical component of the development and progression of several types of cancer. Neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) are simple, inexpensive, and reliable predictors of the systemic inflammatory response to the therapy in different malignant tumors, including colorectal cancer. Methods Metastatic colorectal cancer (mCRC) patients treated with panitumumab plus chemotherapy at first-line at the medical oncology unit of Fondazione Institute for Research, Hospitalization and Health Care (IRCCS) Policlinico San Matteo di Pavia between January 1st 2016 and February 1st 2021 were retrospectively analyzed. NLR and LMR were divided into two groups (high and low) based on the cut-off points, with the estimation of the prognostic accuracy of NLR for the early treatment response as the primary end-point of this study. Results The receiver operating characteristic (ROC) analysis showed a fair prognostic accuracy of NLR for early treatment response (area under the curve (AUC)=0.76, 95% CI: 0.62-0.89). A slightly lower prognostic accuracy was found for LMR (AUC=0.71, 95% CI: 0.57-0.85). In the univariable proportional hazard Cox model, no effect of NLR on PFS was found (NLRHigh vs. NLRLow HR=1.3; 95% CI: 0.7-2.4, p=0.414). Patients with higher levels of LMR showed a trend towards higher PFS (LMRHigh vs. LMRLow HR=0.4; 95% CI: 0.2-1.1, p=0.066). No association was found between NLR (or LMR) and skin toxicity. Conclusions NLR and LMR may be used as biomarkers of prognostic accuracy for the early treatment response in mCRC patients treated with panitumumab.

G-CSF and G-CSF-related vasculitis: a systematic review of the literature and intriguing future research perspectives.

Background: There are several case reports suggesting that G-CSFs may, in rare conditions, produce serious side effects, such as vasculitis. Materials & methods: A systematic search was conducted in Medline via PubMed, Embase and Cochrane Library to describe this unusual side effect to raise awareness among clinicians for early recognition and treatment. Results: Fifty-seven patients were analyzed. The most prevalent cancer type was breast cancer (47%). Long-acting G-CSF was used in 38 patients (67%). Only 47% of patients were treated with steroids. Conclusion: Although the benefit of G-CSF treatment outweighs the potential damage, oncologists should consider the possibility of triggering a vascular toxicity and try to identify patients at increased risk for this side effect.

Lay abstract Background: Several case reports suggest that a type of drug called granulocyte colony-stimulating factor (G-CSFs) may, in rare cases, produce serious side effects, such as vasculitis. Materials & methods: A systematic search was conducted to describe this unusual side effect. Results: Fifty-seven patients were analyzed. The most prevalent cancer type in which this side effect was observed was breast cancer (47%). Only 47% of patients were treated with steroids. The main symptoms, such as fever, chest/epigastric pain and general malaise, are nonspecific and cannot be used to diagnose the side effect; laboratory findings are suggestive of inflammation. Conclusion: Accurate assessment of what causes this adverse event is extremely important. Although the benefit of G-CSF treatment outweighs the potential damage, oncologists should consider the possibility of triggering vascular toxicity and try to identify patients at increased risk.