Triple Combination Therapy With 2 Antivirals and Monoclonal Antibodies for Persistent or Relapsed Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Immunocompromised Patients.

BACKGROUND: Severely immunocompromised patients are at risk for prolonged or relapsed Coronavirus Disease 2019 (COVID-19), leading to increased morbidity and mortality. We aimed to evaluate efficacy and safety of combination treatment in immunocompromised COVID-19 patients. METHODS: We included all immunocompromised patients with prolonged/relapsed COVID-19 treated with combination therapy with 2 antivirals (remdesivir plus nirmatrelvir/ritonavir, or molnupiravir in case of renal failure) plus, if available, anti-spike monoclonal antibodies (mAbs), between February and October 2022. The main outcomes were virological response at day 14 (negative Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2] swab) and virological and clinical response (alive, asymptomatic, with negative SARS-CoV-2 swab) at day 30 and the last follow-up. RESULTS: Overall, 22 patients (Omicron variant in 17/18) were included: 18 received full combination of 2 antivirals and mAbs and 4 received 2 antivirals only; in 20 of 22 (91%) patients, 2 antivirals were nirmatrelvir/ritonavir plus remdesivir. Nineteen (86%) patients had hematological malignancy, and 15 (68%) had received anti-CD20 therapy. All were symptomatic; 8 (36%) required oxygen. Four patients received a second course of combination treatment. The response rate at day 14, day 30, and last follow-up was 75% (15/20 evaluable), 73% (16/22), and 82% (18/22), respectively. Day 14 and 30 response rates were significantly higher when combination therapy included mAbs. Higher number of vaccine doses was associated with better final outcome. Two patients (9%) developed severe side effects (bradycardia leading to remdesivir discontinuation and myocardial infarction). CONCLUSIONS: Combination therapy including 2 antivirals (mainly remdesivir and nirmatrelvir/ritonavir) and mAbs was associated with high rate of virological and clinical response in immunocompromised patients with prolonged/relapsed COVID-19.

Intravenous immunoglobulin bridging to rituximab in NMDAR encephalitis patients non-responders to first-line treatments.

BACKGROUND: The immunotherapy strategy for autoimmune encephalitis is based on several types and schedules of both first- and second-line drugs. Failing to respond to the latter prompts the use of non-conventional rescue therapies, with higher risks of severe adverse effects. We report on a protocol that entails the use of intravenous immunoglobulin cycles to bridge the 4-month period that the second-line drug rituximab needs to exert its full therapeutic effects. METHODS: Three patients with NMDAR encephalitis who were non-responders to first-line treatments entered the study. The protocol consisted of six monthly cycles of intravenous immunoglobulins (IVIG, 0.4 mg/kg/die for 5 days), starting 1 month after the last rituximab infusion (1000 mg at days 0 and 15). Brain MRI and [18F]-FDG-PET were performed at onset and at six and 18 months after onset. RESULTS: In the three patients, substantial improvements of disability or complete recovery were achieved, without modifications over the 30-to-50-month follow-up. No adverse events nor laboratory test abnormalities were recorded. Imaging findings paralleled the favorable disease courses. Brain [18F]-FDG-PET was more sensitive than MRI in detecting abnormalities. DISCUSSION: Our observations suggest that the herein-described protocol might be used in patients with NMDAR encephalitis at risk for poor prognosis in the mid-term when they need to shift to rituximab. [18F]-FDG-PET confirmed to be a sensitive tool to detect the minimal brain lesions that can underlie isolated cognitive and psychiatric symptoms.

Parsonage-Turner syndrome following coronavirus disease 2019 immunization with ChAdOx1-S vaccine: a case report and review of the literature.

BACKGROUND: Parsonage-Turner syndrome is an acute peripheral neuropathy that affects the upper brachial plexus region. Previously published reports demonstrate that the condition can be triggered by surgery, infection, autoimmune diseases, strenuous exercise, trauma, radiation, and vaccination. Parsonage-Turner syndrome has already been reported in three other patients who were vaccinated against coronavirus disease 2019. CASE PRESENTATION: We report the case of a 51-year-old Caucasian man without comorbidities who received the first dose of the ChAdOx1-S recombinant vaccine (Vaxzevria, AstraZeneca, Oxford, UK) against coronavirus disease 2019 and was diagnosed with Parsonage-Turner syndrome. A few days after getting vaccinated, the patient reported a progressive increase in pain in the region of vaccine administration. One month later, the shoulder pain was followed by symptoms of hypoesthesia and muscle weakness on abduction and elevation of the left upper limb. Neurological examination revealed an atrophy of the proximal muscles of the left upper limb, accompanied by paresis of the left deltoid, biceps brachii, triceps brachii, and infraspinatus muscles. Electroneuromyography carried out 3 months after the onset of symptoms showed signs consistent with brachial plexus neuritis. The adverse reaction has been properly reported to the Italian Pharmacovigilance System (Italian Medicines Agency-Agenzia Italiana del Farmaco. CONCLUSION: The increased awareness of such association is essential for early identification and diagnosis and, thus, better clinical outcomes.

Belagenpumatucel-L for the treatment of non-small cell lung cancer.

INTRODUCTION: Immunotherapy has become a promising approach for the treatment of NSCLC. In order to stimulate the host immune system against tumour antigens, several cancer vaccines have been generated and evaluated. Belagenpumatucel-L is a whole tumour cell vaccine expressing the antisense strand of the TGF-ß2 gene. AREAS COVERED: The purpose of this article is to review the most relevant findings of clinical trials testing belagenpumatucel-L in advanced NSCLC patients. EXPERT OPINION: Although the Phase III trial investigating belagenpumatucel-L in stage III/IV patients did not meet its primary end point, a survival benefit was observed in several subgroups of patients. Further studies are needed in order to select patients who may benefit from this vaccine.

Oral vinorelbine in the treatment of non-small-cell lung cancer.

INTRODUCTION: Originally formulated as an intravenous (i.v.) agent, vinorelbine is also currently available as an oral chemotherapeutic agent. Oral vinorelbine has demonstrated significant activity in different settings for NSCLC, including adjuvant treatment for resected disease, concurrent chemoradiation for locally advanced NSCLC and palliative chemotherapy for recurrent/metastatic NSCLC, as part of combination schedules or as a single-agent treatment. AREAS COVERED: The authors explored the available data describing the use of oral vinorelbine in NSCLC. PubMed articles and abstracts presented at international conferences were analysed, and relevant trials were reported and discussed. Specific settings, including the treatment of elderly and unfit patients and metronomic schedules including oral vinorelbine, were evaluated. Available pharmacoeconomic data were also assessed. EXPERT OPINION: Oral vinorelbine is an appealing agent, particularly as part of combination regimens containing platinum derivatives, although it can have a role as a single-agent treatment as well. Its safety profile is generally favourable and its route of administration is generally preferred by patients receiving chemotherapy. Compared to i.v. vinorelbine and other antineoplastic agents, oral vinorelbine has been reported to be advantageous in terms of cost savings.

Free drugs in clinical trials and their potential cost saving impact on the National Health Service: a retrospective cost analysis in Italy.

BACKGROUND: The cost of new anti-cancer drugs has dramatically increased in recent years, and countermeasures are required in order to limit pharmaceutical expenses. Sponsored clinical trials that provide drugs free of charge may be a useful tool in order to reduce drug costs. The aim of this analysis is to evaluate the effect of clinical trials on pharmaceutical expenditure savings. METHODS: We evaluated the cost of drugs administered in clinical practice and in clinical trials (considering only the standard regimens that were administered also in clinical practice) in 2010 at the Lung Cancer Unit of the National Institute for Cancer Research in Genoa, Italy. The cost of drugs was calculated on the price charged at our Institute in 2010. The supposed cost of experimental treatment replacing standard therapy was converted in the cost of the treatments that would have been chosen in clinical practice, considering histology, line of treatment and number of administered cycles. RESULTS: From 1/1/2010 to 12/31/2010, 196 patients affected by lung cancer or pleural mesothelioma were treated. 152 patients (78%) received treatment in clinical practice or in non-sponsored trials (18 patients in 4 trials), while 44 (22%) were treated in one of the 12 sponsored clinical trials recruiting in 2010. Globally, 606 cycles of treatment would have been administered to patients, of which 436 (72%) were administered in clinical practice or in non-sponsored trials and 170 (28%) were administered in pharmaceutical company sponsored clinical trials. The overall cost of those anti-neoplastic drugs, based on the prices charged at our Institute in 2010, was €799 803. The cost of drugs administered in clinical practice or in non-sponsored trials was €556 649 (70%), whereas the cost of standard drugs administered in clinical trials was €243 154 (30%). The grants provided by pharmaceutical companies were evaluated and amounted to €235 965. CONCLUSIONS: The participation in sponsored clinical trials in which drugs are provided free of charge offers substantial cost savings for the National Health Service; moreover, the grants received for each enrolled patient produced additional income.