Safety Of Immunotherapy In Patients Research Articles

Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis.

Gastric cancer (GC) is the fifth most common type of cancer and has the fourth highest death rate among all cancers. There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC. To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC. This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023. The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method. The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases. The analysis comprised 48 patients diagnosed with advanced GC, who were categorized into two groups: A liver metastasis cohort (n = 20) and a non-liver metastatic cohort (n = 28). Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis. The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0% and 35.7% (P > 0.05), respectively. Similarly, the disease control rates in these two cohorts were 65.0% and 82.1% (P > 0.05), respectively. The median progression-free survival was 5.0 months in one group and 11.2 months in the other group, with a hazard ratio of 0.40 and a significance level (P) less than 0.05. The median overall survival was 12.0 months in one group and 19.0 months in the other group, with a significance level (P) greater than 0.05. Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.

Efficacy and safety of pembrolizumab as first-line treatment for advanced non-small cell lung cancer complicated with chronic obstructive pulmonary disease: protocol for a prospective, single-arm, single-center, phase II clinical trial.

The first-line standard treatment option for patients with NSCLC complicated with Chronic obstructive pulmonary disease (COPD) is still unclear and relies on the treatment option of NSCLC alone. To date, a limited number of retrospective studies have explored the efficacy and safety of immunotherapy in patients with NSCLC complicated with COPD. We therefore designed this study to further explore the efficacy and safety of first-line immunotherapy in patients with NSCLC complicated with COPD. This study was designed as a single-armed, single-center, prospective, phase II clinical study. It will include 30 advanced (stage IV) NSCLC combined with COPD primary treatment subjects. Each subject's diagnosis will be confirmed by clinical, radiographic, pathologic, and pulmonary function evaluation. A fixed dose of 200 mg pembrolizumab will be administered by intravenous infusion on day1 every 3 weeks (Q3W). The management of stable and acute exacerbations of COPD include home oxygen therapy, and the use of conventional medications are also administered. Imaging evaluation will be performed every 6 weeks for 6 months from the first pembrolizumab dose and approximately every 12 weeks thereafter until disease progression or early withdrawal. COPD status will be evaluated every 3 months by pulmonary function, GOLD grading, mMRC score, CAT score, ABCD grouping, and AECOPD severity. The primary outcome is Progression-free survival. The secondary outcome measures include objective response rate, overall survival, rate of acute exacerbations of COPD (times/year), lung function, mMRC score, CAT score, impact of treatment on patient's health-related quality of life, antibiotic use (including duration and classes), and adverse events associated with immune checkpoint inhibitors. Exploratory endpoint is to explore the association between COPD grade and the degree of immune cell (CD4+ T lymphocytes and CD8+ T lymphocytes) infiltration, as well as the association between COPD grade and the efficacy of immune checkpoint inhibitors. ClinicalTrials.gov, identifier NCT05578222.

Immunotherapy in Elderly Patients-Single-Center Experience.

Cancer management faces a substantial challenge posed by the aging demographic. Aging is marked by accumulated DNA damage, and this phenomenon is implicated in the process of tumorigenesis. The concept of immunosenescence, postulated to manifest in elderly individuals, is defined by an age-related decline in T cells and a simultaneous elevation in proinflammatory status, leading to a diminished efficacy in response to immunotherapy. Notably, despite the rising prevalence of cancer in the elderly population, their underrepresentation in clinical trials persists. This underscores the unmet need to evaluate the safety and efficacy of cancer treatment in the elderly. This retrospective, single-center cohort study aimed to assess and evaluate the effectiveness and safety of immunotherapy in patients compared to younger individuals with metastatic solid tumors receiving ICI. A total of 220 patients were included, mostly males, with a median age of 64. The proportion of patients ≥ 65 years old was 56.5%. The use of ICI showed no significant differences concerning overall survival (OS) and progression-free survival (PFS) among age groups across different cancer types (melanoma, non-small-cell lung cancer (NSCLC), renal, and bladder cancer; p = 0.388). Concerning the response to treatment in renal cancer patients, a significant difference was observed (p = 0.041), suggesting a potential negative impact of age on the treatment response. In patients that presented immune-related adverse events (irAEs), oral corticosteroid therapy was marginally associated (p = 0.059) with the elderly population. When evaluating the NSCLC population alone (n = 131, 59.5%), our study revealed a strong association between the development of irAEs, patients' PFS and OS, and the duration of ICI treatment, but not directly correlated with age. The NSCLC elderly population presented a marginally greater number of irAEs, although without statistical significance (p = 0.86). ICI maintained efficacy and safety in elderly patients, challenging the notion that age alone should determine treatment decisions. The findings emphasize the necessity of a comprehensive geriatric assessment rather than relying solely on chronological age for personalized cancer treatment in the elderly population. Further prospective studies are needed to better understand immune responses in older adults and derive predictive biomarkers for cancer treatment.

Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study

Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce. This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit. Long-term benefit was defined as progression-free survival (PFS) exceeding 24 months. All patients who received immunotherapy for an MMRd/MSI mCRC were included. Patients who received immunotherapy in combination with another known effective therapeutic class agent (chemotherapy or tailored therapy) were excluded. Overall, 284 patients across 19 tertiary cancer centers were included. After a median follow-up of 26.8 months, the median overall survival (mOS) was 65.4 months [95% confidence interval (CI) 53.8 months-not reached (NR)] and the median PFS (mPFS) was 37.9 months (95% CI 30.9 months-NR). There was no difference in terms of efficacy or toxicity between patients treated in the real-world or as part of a clinical trial. Overall, 46.6% of patients had long-term benefit. Independent markers associated with long-term benefit were Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 (P= 0.025) and absence of peritoneal metastases (P= 0.009). Our study confirms the efficacy and safety of immunotherapy in patients with advanced MMRd/MSI CRC in the routine clinical practice. ECOG-PS score and absence of peritoneal metastases provide simple markers that could help identify patients who benefit the most from this treatment.

Clinical analysis of combined immunotherapy in patients with malignant pleural mesothelioma

Objective: To observe the present situation, efficacy and safety of immunotherapy in patients with malignant pleural mesothelioma (MPM). Methods: The data of 39 patients with MPM in two centers from 2016 to 2021 were collected and the efficacy and safety were evaluated. According to the application of immune checkpoint inhibitors (ICIs), these patients, whose median clinical follow-up amounting to 18.97 months, were divided into immunotherapy group (19 cases) and control group (20 cases). Kaplan-Meier method and Log-rank test were used for the survival analysis. Results: The objective response rate (ORR) and the disease control rate (DCR) in the immunotherapy group is 21.05% and 79.0% respectively, compared with 10.0% and 55.0% in the control group; and the difference was not statistically significant (P>0.05). The median overall survival (OS) in the immunotherapy group was significantly longer than that in the control group (14.53 months vs 7.07 months, P=0.015), but there was no significant difference in the median progression free survival (PFS) between two groups (4.80 months vs 2.03 months, P=0.062). Single factor survival analysis showed that the nature of pleural effusion, pathological subtype and the efficacy of immunotherapy were related to both PFS and OS of the patients with MPM (P<0.05). The incidence of adverse reactions in immunotherapy group was 89.5% (17 out of 19 cases), and the most common adverse event was hematological toxicity (9 cases), followed by nausea and vomiting (7 cases), fatigue (6 cases) and skin damage (6 cases). Five patients had immune checkpoint inhibitors (ICIs) related adverse reactions with grade 1-2. Conclusions: Patients with MPM have begun to receive immunotherapy in more than 2-line mainly combined chemotherapy in the real world, and the median treatment line is 2-line. Either combined with chemotherapy or anti-angiogenesis therapy, ICI inhibitors have significant efficacy, controllable adverse events and good clinical value.

Variation of renal function in patients with urothelial carcinoma treated by tislelizumab-based immunochemotherapy.

494 Background: Treatment based on PD-1 ICIs brings advances to the treatment of urothelial carcinoma (UC). Although acute renal insufficiency is not common in iRAEs, the safety of immunotherapy in patients with renal impairment is still unknown. Consequently, we intend to investigate the effect of immunochemotherapy on nephritic function in the short term. Methods: Between July 2019 and September 2022, data of patients (pts) with UC that underwent tislelizumab based immunochemotherapy, including demographic information (age, gender), and creatinine level in baseline, after the first, second and third cycle (C1, C2 and C3) of immunotherapy in the Second Hospital of Tianjin medical University was collected and analyzed retrospectively. Estimated glomerular filtration rate (eGFR) is calculated according to CKD-EPI formula 2009, while pts were subdivided into different groups according to baseline eGFR, referencing to CKD categories in the K-DIGO 2012 guidelines for CKD classes. Data analyses were conducted using paired samples Wilcoxon Signed Rank Test and Kruskal-Wallis H test. Results: 163 pts have been included in our analyse totally. The median age was 67 years (IQR 61-74) and 128 (78.5%) were male. 135 (82%) pts received ICIs as perioperative treatment, while 19 (12%) pts were treated after radical operation. Metastasis is found in 9 (6%) pts before firstly received immunotherapy. Median creatinine (Cr) in baseline was 80.2umol/L (IQR 68.3-95.8), while median EGFR was 82.6 (IQR 64.3-93.8) mL/min/1. 73m2 in all pts. According to CKD categories in the K-DIGO 2012 guidelines, at baseline, 57 pts are classified as G1 (eGFR≥90 mL/min/1.73m2), 74 pts as G2(eGFR &lt;90 mL/min/1.73 m2 and≥60 mL/min/1.73 m2), 30 as G3 (eGFR &lt;60 mL/min/1.73 m2 and≥30 mL/min/1.73 m2), and 2 as G4 (eGFR &lt;30 mL/min/1.73 m2 and≥15 mL/min/1.73 m2). No significant difference in eGFR between pts with CKD G1-2 in comparison to baseline and after the first (C1), second (C2) or third cycle(C3) of tislelizumab based immunotherapy (All p &gt;0.05). Notably, we found that eGFR improved in pts with CKD G3-4 when the first, second and third cycle completed, in comparison to the baseline.(p&lt;0.001, &lt;0.001, =0.002). Conclusions: Despite renal impairment is common in pts with UC, no evidence suggests that it is contraindicated for tislelizumab based treatment. More importantly, PD-1 immunotherapy may provide better nephritic benefits in patients with renal insufficiency. [Table: see text]

Effectiveness and safety of allergen immunotherapy in patients with allergic rhinitis complicated by rheumatic autoimmune diseases: a case series study

BackgroundAllergen immunotherapy (AIT) is the only treatment that has modified the natural history of allergic diseases. However, since its overall effect on the immune system has not been elucidated, AIT is either absolutely or relatively contraindicated in patients with rheumatic autoimmune diseases (RADs). Therefore, there have been no long-term observations of patients with RADs receiving AIT; thus, the effectiveness and safety of AIT in these patients remain unclear.MethodsThis was a single-center retrospective observational study. RAD patients receiving AIT for allergic rhinitis at our institution were selected. Changes in the activity of RAD patients were investigated for 2 years from baseline, including those who discontinued AIT. The effectiveness of AIT was also investigated using the Japan Allergic Rhinitis Standard Quality of Life Questionnaire.ResultsThirteen patients with RADs were enrolled in the study. All patients received sublingual immunotherapy, of which four discontinued AIT owing to adverse events. Among all patients, the symptoms of RADs in three patients worsened during the observation period; however, none of them were causally related to AIT. Most of the adverse events associated with AIT were mild, in which only one patient required drug intervention due to worsening rhinitis symptoms. In the nine patients who were able to continue AIT, their eye and nasal symptom scores showed a significant improvement from 1.67 (1.5–2.0) at baseline to 0.67 (0–1.17) in the 2nd year of treatment (p = 0.0141).ConclusionsAIT is a safe and effective treatment modality for patients with allergic rhinitis complicated by RADs.

Brief Report of Anti–Programmed Cell Death Protein-1 in Human Immunodeficiency Virus Setting: Relevant and Breaking Results in First-Line NSCLC Therapy

In the recent past, we observed an increased risk of cancer in the population with human immunodeficiency virus (HIV) owing to the development of antiretroviral therapies that decreased mortality caused by HIV-specific infections. This particularly fragile population is frequently excluded from clinical trials, and up-to-date recommendations for these patients are lacking. Only few cases of patients with HIV suffering from cancer and undergoing first-line immunotherapy have been reported so far. Here, we report the largest known study of patients with HIV with NSCLC (five patients) undergoing first-line immunotherapy by pembrolizumab, after CANCERVIH group selection. Our results are consistent with those of previous case reports concerning safety of immunotherapy in patients with HIV, revealing no severe or fatal toxicity, opportunistic infections, or immune reconstitution inflammatory syndrome. Moreover, pembrolizumab did not seem to modify HIV viral parameters. We also evaluated the effectiveness of immunotherapy in these HIV-immunosuppressed patients: the average survival was 9.8 months, with three patients having rapid progression and two partial response. Nevertheless, besides safety and drug-to-drug interactions, the effectiveness of first-line immunotherapy in people living with HIV needs to be supported by larger studies.

The efficiency and safety of immune checkpoint inhibitors in the treatment of small cell lung cancer: a meta-analysis.

Small cell lung cancer (SCLC) is highly invasive and fatal, sensitive to chemotherapy and radiotherapy but prone to relapse, with a poor overall survival rate. It is particularly urgent for SCLC patients to receive effective follow-up treatment. In the past 20 years, there has been no breakthrough in clinical treatment of SCLC. Currently, clinical studies on immunotherapy for SCLC with extensive stage disease (ED) have achieved good efficacy, bringing new hope for the treatment of small-cell lung cancer. PD-1 inhibitors used to treat small cell lung cancer include Pembrolizumab and Nivolumab. PD-L1 inhibitors mainly include Atezolizumab and Durvalumab. Other PD-1/PD-L1 inhibitors, such as Avelumab, are currently being tried for SCLC and the results have not yet been published. This study is to evaluate the efficacy and safety of immunotherapy in patients with ED SCLC. A literature search of the PubMed, Embase, and Cochrane Library databases were performed. Two reviewers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. RevMan 5.3 software was used for meta-analysis. Four studies involving 1,981 patients with ED SCLC were included. Both overall survival (OS) [hazard ratio (HR) =0.80, 95% confidence interval (CI) (0.68, 0.95), P=0.009] and progression-free survival (PFS) [HR =0.82, 95% CI (0.75, 0.90), P<0.00001] were longer in the immunotherapy group than in the chemotherapy group. The incidence of total treatment-related adverse events in the immunotherapy group were lower than those in the chemotherapy group [relative risk (RR) =1.050, 95% CI (1.010, 1.080), P=0.007], and the differences were statistically significant. Immunotherapy has better efficacy and safety than chemotherapy for the treatment of ED SCLC.

Safety and efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer and hepatitis B or hepatitis C infection

ObjectivesThe safety and efficacy of immunotherapy among patients with history of hepatitis B (HBV) or hepatitis C virus (HCV) infection and non-small cell lung cancer (NSCLC) remains unclear as this population has traditionally been excluded from clinical trials with immune checkpoint inhibitors (ICIs). Materials and methodsWe retrospectively evaluated treatment toxicities and clinical outcomes in nineteen patients with NSCLC and history of past or chronic HBV (16 cases, two of these had HCV co-infection) or chronic HCV infection (five cases), who received a programmed death-1 (PD-1) pathway inhibitor. ResultsThe overall response rate to immunotherapy was 35 %, and the median progression-free survival was 4.5 months. After ICI initiation, increases in liver function tests (LFTs) from baseline were infrequent and mild, and no patients experienced grade 3 or 4 hepatic immune-related adverse events or required ICI discontinuation or corticosteroid administration for management of hepatic toxicity. There were no significant changes in viral load or cases of HBV reactivation or HCV flare while on ICI therapy. ConclusionIn this case series, treatment with immunotherapy in patients with NSCLC and past or chronic viral hepatitis appears to be safe, and responses to ICIs can be durable in this population. Additional studies are needed in larger cohorts of patients to determine the safety of immunotherapy in patients with chronic viral infections.

Immunotherapy (excluding checkpoint inhibitors) for stage I to III non-small cell lung cancer treated with surgery or radiotherapy with curative intent.

Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for approximately 80% to 85% of all cases. For patients with localised NSCLC (stages I to III), it has been speculated that immunotherapy may be helpful for reducing postoperative recurrence rates, or improving the clinical outcomes of current treatment for unresectable tumours. While several new agents have now entered phase III clinical trials, we felt a systematic review was needed to address the question of the effectiveness and safety of immunotherapy in patients with stages I to III NSCLC. To evaluate the effectiveness and safety of immunotherapy (excluding checkpoint inhibitors) in patients with localised NSCLC (stages I to III) who received surgery or radiotherapy with curative intent. We searched the following databases (from inception to 20 January 2017): CENTRAL, MEDLINE, Embase, and CINAHL, and five trial registers. We also manually checked abstracts or reports from relevant conference proceedings and the reference lists of included trials. We searched for randomised controlled trials (RCTs) in adults (≥ 18 years) with histologically-confirmed early-stage (stages I to III) NSCLC after surgical resection, and those with unresectable locally advanced stage III NSCLC who had received radiotherapy with curative intent. For patients who had received primary surgical treatment, postoperative radiotherapy or chemoradiotherapy was allowed if it was used for both experimental and control groups. Two review authors independently selected eligible trials, assessed risk of bias, and extracted data. We used survival analysis to pool time-to-event data, expressing the intervention effect as a hazard ratio (HR). We calculated risk ratios (RR) for dichotomous data, and mean differences for continuous data, with 95% confidence intervals (CI). Due to clinical heterogeneity (immunotherapeutic agents with different underlying mechanisms), we used random-effects models for our meta-analyses. We identified nine eligible trials that randomised 4940 participants, who had received surgical resection or curative radiotherapy, to either an immunotherapy group or a control group. Included immunological interventions were active immunotherapy (i.e. Bacillus Calmette-Guérin (BCG)), adoptive cell transfer (i.e. transfer factor (TF), tumour-infiltrating lymphocytes (TIL), dendritic cell-cytokine induced killer (DC-CIK), and antigen-specific cancer vaccines (melanoma-associated antigen 3 (MAGE-A3) and L-BLP25). Except for one small trial, which provided insufficient information for risk assessment, we assessed five studies at high risk of bias for at least one of the seven biases studied; we considered the risk of bias in the other three trials to be low. We included data from seven of the nine trials in the meta-analyses (4695 participants). We pooled data from 3693 participants from the three high quality RCTs to evaluate overall survival (OS) and progression-free survival (PFS). We found a small, but not statistically significant, improvement in OS (HR 0.94, 95% CI 0.83 to 1.06; P = 0.35), and PFS (HR 0.93, 95% CI 0.81 to 1.07; P = 0.19; high-quality evidence). The addition of immunotherapy resulted in a small, but not statistically significant, increased risk of having any adverse event (RR 1.15, 95% CI 0.97 to 1.37; P = 0.11, three trials, 3955 evaluated participants, moderate-quality evidence), or severe adverse events (RR 1.10, 95% CI 0.88 to 1.39; four trials, 4362 evaluated participants; low-quality evidence).We analysed data from six studies for one-, two-, and three-year survival rates (4265 participants), and from six studies for five-year survival rates (4234 participants). We observed no clear between-group differences (low-quality evidence for one- and two-year survival rates, and moderate-quality evidence for three- and five-year survival rate).No trial reported the overall response rates; only one trial provided health-related quality of life results. The current literature does not provide evidence that suggests a survival benefit from adding immunotherapy (excluding checkpoint inhibitors) to conventional curative surgery or radiotherapy, for patients with localised NSCLC (stages I to III). The addition of vaccine-based immunotherapy might increase the risk of adverse events. Several ongoing trials with immune checkpoints inhibitors (PD-1/PD-L1) might bring new insights for role of immunotherapy for patients with stages I to III NSCLC.

The efficacy and safety of immunotherapy in patients with advanced NSCLC: a systematic review and meta-analysis.

Immunotherapy is a novel treatment for advanced non-small cell lung cancer (NSCLC) patients. Immunotherapy includes two main broad classes of therapeutic vaccines and immune checkpoint inhibitors, as well as cytokines, biological response modifiers and cellular therapy. The present systematic review and meta-analysis aims to evaluate the efficacy and safety of different classes of immunotherapy in patients with advanced NSCLC. Literature search was done on Medline, Embase and Cochrane Library. The primary endpoints were overall survival (OS) and grade ≥3 adverse events. Twenty randomized controlled trials were finally identified in our study. Efficacy analysis indicated an improvement of OS in advanced NSCLC patients after treating by therapeutic vaccines and immune checkpoint inhibitors, but not for other immunomodulators. Safety analysis showed that immunotherapy was well-tolerated. All kinds of grade ≥3 adverse events were similar between experimental group and control group except that neutropenia and thrombocytopenia had a higher incidence in patients received vaccines. In conclusion, immunotherapy is a promising treatment for advanced NSCLC patients. Our findings will be further confirmed and supplemented by several phase II and phase III RCTs which are going to complete in near future.

Safety of immunotherapy in patients with rhinitis, asthma or atopic dermatitis using an ultra-rush buildup. A retrospective study

BackgroundAllergen-specific immunotherapy is a proven, highly effective treatment for IgE–mediated diseases. However, ultra-rush immunotherapy is prescribed infrequently because of the perception that accelerated immunotherapy buildup leads to a higher rate of systemic reactions. ObjectiveTo evaluate the frequency of adverse reactions in patients with IgE–mediated diseases receiving house dust mite (HDM) ultra-rush immunotherapy. MethodsA retrospective, observational study was conducted for patients with IgE–mediated diseases receiving allergen-specific immunotherapy. Subcutaneous immunotherapy with depigmented polymerized mites extract was administered in two refracted doses of 0.2 and 0.3ml at first injection, and in single 0.5ml doses in subsequent monthly injections. A 30min observation time was required after each injection. Systemic reactions were graded using the World Allergy Organisation grading system. Results575 patients were included. The age range was 1–83 years. Most patients had respiratory diseases (544) and 101 patients had atopic dermatitis. A total of 27 patients (4.6%) experienced 139 reactions (reactions/injections: 1.9%); 22 patients (3.8%) experienced 134 local reactions (local reactions/injections: 1.8%). Eight patients (1.3%) experienced eight systemic reactions (systemic reactions/injections: 0.1%). Five systemic reactions were grade 2 and three grade 1. Two systemic reactions were reported during buildup. There were no fatalities. ConclusionTaking into account the possible bias for the retrospective design of this study we observed that immunotherapy for patients with IgE–mediated diseases using a depigmented polymerized mites extract, with an ultra-rush buildup, has similar frequency of systemic reactions than that seen in slower buildup immunotherapy in other studies. Accelerated buildup could improve patients’ adherence and reduce dropout rates.

Treatment of advanced renal cell carcinoma with tumor lysate pulsed IL-12 secreting autologous dendritic cells

14585 Background: We have conducted a clinical phase I trial to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with advanced renal cell carcinoma (RCC). As opposed to previous cancer vaccination studies, dendritic cells were specifically enabled to secrete interleukin 12 (IL-12). Methods: Patients with advanced RCC (n = 11) received six weekly intranodal vaccinations with autologous monocyte-derived dendritic cells (mDCs). MDCs were loaded with autologous tumor cell lysate and were specifically stimulated to secrete IL-12 to polarize type-1 T-helper lymphocytes (Th1) and to directly present tumor antigens to cytotoxic T lymphocytes (CTL). Results: There was no significant treatment-related toxicity and no clinical evidence of autoimmunity. Vaccination was very well tolerated. Five patients had stable disease for at least five months, while four patients had progressive disease. Two patients with early clinically significant disease progression had to be excluded before completion of the treatment. In addition, we could detect enhanced anti-tumor immunity in vitro comparing immune response before versus after cancer vaccination. Conclusions: Our findings indicate that cancer vaccination with IL-12 secreting mDCs is well tolerated and has potential clinical and clear immunological effects in patients with advanced RCC. No significant financial relationships to disclose.

Effect of pretreatment with fexofenadine on the safety of immunotherapy in patients with allergic rhinitis

Allergen-specific immunotherapy, although not a cure, remains the only treatment available that can alter the natural course of an allergic disease. However, the risk of allergen specific immunotherapy-related systemic reactions (SRs), reported to occur in approximately 1% to 14% of patients and which can range from mild to fatal in seriousness, represents a barrier to implementing this unique and effective treatment option. To explore the possibility that pretreatment with the H1-antihistamine fexofenadine could prevent the occurrence of severe SRs induced by immunotherapy in Japanese patients with allergic rhinitis. In this open-label, multicenter study, 134 patients receiving immunotherapy for allergic rhinitis were randomized 1:1 to a group receiving pretreatment with fexofenadine hydrochloride (60 mg) 2 hours before immunization injection (n = 67) or to a control group receiving no pretreatment (n = 67). Patients were further grouped into those who received cedar pollen immunotherapy and those who received dust mite immunotherapy. Pretreatment with fexofenadine 2 hours before immunotherapy significantly reduced the occurrence of severe SRs (P = .03), significantly increased the proportion of patients receiving cedar pollen immunotherapy who achieved the target maintenance dose (TMD) (P = .03), and significantly reduced the length of time to attain the TMD (P = .047 and P = .003 for patients receiving cedar pollen and dust mite immunotherapy, respectively). This study suggests a novel role for fexofenadine in enhancing the safety of immunotherapy and increasing the proportion of patients achieving the TMD.

The Safety of Immunotherapy in Patients with Allergic Asthma and Allergic Rhinitis

We studied systemic reactions associated with immunotherapy in a group of 50 patients with mean age 31.4 years. The group consisted of 36 women and 14 men who followed a three-year immunotherapy treatment with pollen and mite allergen extracts (HAL-Holland Corporation). A total number of 2550 injections were administered. Eight patients developed systemic reactions; 6 had allergic rhinitis and 2 allergic asthma. None developed severe anaphylaxis. Seven of the systemic reactions occurred immediately after injection while one was a late reaction manifested as generalized urticaria, local edema and rubor at the site of the injection. From the 7 patients who showed an immediate reaction, 5 developed generalized urticaria with local edema and rubor at the site of the injection, while 2 presented with bronchial spasm. We did not observe any reaction when the quantity of the extract injection was reduced by 50%. Our study points out that, in the vast majority of cases, immunotherapy is free of severe systemic reactions. Those that occur are associated with the injection of high-density extracts and none of them is severe.