Summary Patients affected by lymphoid malignancies (LM) are frequently immune‐compromised, suffering increased mortality from COVID‐19. This prospective study evaluated serological and T‐cell responses after complete mRNA vaccination in 263 patients affected by chronic lymphocytic leukaemia, B‐ and T‐cell lymphomas and multiple myeloma. Results were compared with those of 167 healthy subjects matched for age and sex. Overall, patient seroconversion rate was 64·6%: serological response was lower in those receiving anti‐cancer treatments in the 12 months before vaccination: 55% vs 81·9% ( P < 0·001). Anti‐CD20 antibody plus chemotherapy treatment was associated with the lowest seroconversion rate: 17·6% vs. 71·2% ( P < 0·001). In the multivariate analysis conducted in the subgroup of patients on active treatment, independent predictors for seroconversion were: anti‐CD20 treatment ( P < 0·001), aggressive B‐cell lymphoma diagnosis ( P = 0·002), and immunoglobulin M levels <40 mg/dl ( P = 0·030). The T‐cell response was evaluated in 99 patients and detected in 85 of them (86%). Of note, 74% of seronegative patients had a T‐cell response, but both cellular and humoral responses were absent in 13·1% of cases. Our findings raise some concerns about the protection that patients with LM, particularly those receiving anti‐CD20 antibodies, may gain from vaccination. These patients should strictly maintain all the protective measures.

Background: In clinical trials, the expansion and persistence of CAR-T cells correlate with therapeutic efficacy. However, properties of CAR-T cells that enable their in vivo proliferation have still to be consistently defined and the role of CAR-T bag content has never been investigated in a real life setting. Experimental Design: Residual cells obtained after washing 61 anti-CD19 CAR-T product bags were analysed to identify tisagenlecleucel/Tisa-cel and axicabtagene ciloleucel/Axi-cel phenotypic features associated with post-infusion CAR-T cell in vivo expansion and with response and survival. Results: While Tisa-cel was characterized by a significant enrichment in CAR+CD4+ T cells with central memory (P&lt;0.005) and effector (P&lt;0.005) phenotypes and lower rates of CAR+CD8+ with effector memory (P&lt;0.005) and naive-like (P&lt;0.05) phenotypes as compared to Axi-cel, the two products displayed similar expansion kinetics. In vivo CAR-T cell expansion was influenced by the presence of CAR-T with a CD8+ T central memory signature (P&lt;0.005) in both Tisa-cel and Axi-cel infusion products and was positively associated with response and progression-free survival (P&lt;0.05). Conclusions: Our data indicate that despite the great heterogeneity of Tisa-cel and Axi-cel products, the differentiation status of the infused cells mediates CAR-T cell in vivo proliferation that is necessary for anti tumor response.

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Background: Previous data, mostly from clinical trials, reported that HER2-low status is associated with low pathological complete response (pCR), and favourable prognosis. Since these findings suggest the existence of an additional breast cancer subtype, we questioned if the predictive/prognostic value of HER2-low was also relevant in the real world.Methods: Data from non-metastatic breast cancer patients treated with neoadjuvant chemotherapy and surgery (2009–2020) were retrieved from our institutional prospectively-maintained registry. Univariable and multivariable logistic models were implemented to study the association between pCR and baseline HER2 status. Univariable analysis of disease-free survival (DFS) was performed through Kaplan-Meier survival curves and log-rank tests.Results: Starting from a total of 790 consecutive cases, we identified 444 newly-diagnosed breast cancer patients featuring HER2 immunohistochemistry (IHC) 0 (HER2-0, n = 109), and 1 + or IHC 2+/in situ hybridization negative (HER2-low, n = 335) receiving anthracycline and taxane-based regimens in 88.9% of cases. Most of the patients were diagnosed with stage II (67.3%) and there was no difference of disease presentation according to HER2-status. pCR was attained by 71 (16.0%) patients and was significantly associated with increased DFS (p = 0.031). Compared to HER2-0, HER2-low cases were more likely hormone receptor-positive (81.2% vs. 43.1%, p &lt; 0.001), well-differentiated (47.5% vs. 26.6%, p = 0.001), less proliferative (21.5% vs. 8.3%, p = 0.001) and less responsive to treatment (pCR 11.6% vs. 29.4%, p &lt; 0.0001). There was no difference in DFS according to HER2 status, though hormone-receptor (HR) negative/HER2-low cases tended to have a worse prognosis compared to HR-negative/HER2-0. By pCR achievement, 3-years DFS was 87.5.% (75.1–100%) vs. 71.6% (65.9–77.8%) (p = 0.161) in HER2-low and 89.1% (75.8–100%) vs. 72.1% (59.7–87.0%) (p = 0.092) in HER2-0.Conclusion: Our real-world data show that HER2-low breast cancer patients represent roughly a half of the cases treated with neoadjuvant therapy, and have poor treatment response. In absence of pCR, HER2-low breast cancer patients have a dismal prognosis, especially when primary tumor hormone receptor status is negative. Studies are therefore needed to define the biology of these tumors for new therapeutic targets and to incorporate HER2-targeting agents in early-stage treatment.

Purpose: Inflammatory biomarkers and neutrophil-to-lymphocyte ratio (NLR) are associated with prognosis in several tumors. Data on sarcomas are limited, and insufficient on retroperitoneal sarcoma (RPS). Experimental Design: Patients with primary RPS operated between 2002 and 2016 were included. Hemoglobin, monocytes, NLR, platelet-to-lymphocyte ratio (PLR) were retrieved and analyzed both individually and combined into a prognostic index (IBPI). Correlation with clinicopathologic variables was studied, as well as postoperative morbidity according to NLR and IBPI risk categories. The association between overall survival (OS) and biomarkers and, in addition, the 7-year Sarculator-predicted OS probability (pOS) was analyzed using univariable and multivariable Cox models. Results: 423/463 patients had complete data. The median follow-up was 84 months. The median NLR was 3.3 (IQR, 2.4-4.7), with significant variation across histologies. NLR was the only biomarker that independently predicted OS (HR 1.2, 95% CI 1.03 – 1.40; p=0.02). The IBPI showed good discrimination for subgroups at different OS (log-rank test p &lt;0.0001). The Cox model for pOS alone showed a 7-year Index of Prediction Accuracy of 26.9, which increased to 29.5 when IBPI was added to pOS as a complementary prognostic tool. IBPI was also associated with the risk of serious infectious postoperative complications (p=0.0094; non-infectious complications, p=0.6463). Conclusions: NLR was an independent prognostic factor for OS in RPS. When combined into a prognostic index with hemoglobin, monocytes, and PLR, it serves as a readily available prognostic tool addressing tumor-related inflammation and helps in classifying RPS risk in addition to the Sarculator nomogram.