Safety of mRNA-COVID-19 Vaccines in Patients With Thoracic Cancers.

BACKGROUND: Pivotal trials of COVID-19 vaccines did not include cancer patients with questions remaining in this population. Particularly in patients with thoracic malignancies receiving anticancer treatments, the safety of these vaccines has so far been little investigated. METHODS: This is a prospective trial of patients with thoracic cancer receiving anticancer treatments and COVID-19 vaccines at the Division of Thoracic Oncology of European Institute of Oncology between February and September 2021. RESULTS: A total 207 patients affected by thoracic cancers (199 lung cancers and 8 mesotheliomas) had received Covid-19 vaccines (206 mRNA vaccines and 1 virus-vectored vaccine). The majority of patients had at least one comorbidity (76.3%). They were concomitantly treating with targeted therapy (TT) (45.9%), immunotherapy (IO) (22.7%), and chemotherapy (CT) (14%). A total of 64 AEs (15.6%) were observed after administration of Sars-Cov-2 vaccine. The majority of AEs were grade 1 [G1] (6.3%) and G2 (8.8%), only two events were G3 (0.5%). The median follow-up was 9 months (range 1-22 months), during this follow-up 21 patients (10.1%) had a positive nasal swab, most of the patients were asymptomatic (67%) and the symptomatic ones (33%) had mild symptoms and fewer complications and hospitalizations. CONCLUSIONS: COVID-19 m-RNA vaccines appear to be safe in the cohort of patients with thoracic malignances in active treatment, including those receiving immunotherapy. Considering the high morbidity and mortality associated with COVID-19 in patients with lung cancer receiving active treatments, our study supports the current vaccine prioritization, third and/or fourth dose, of all cancer patients with active treatment.

Immune thrombocytopenia during COVID-19 pandemic: An italian monocentric experience

Background : Since the pandemic caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV2), known as COVID-19, has started in February 2020, different cases of immune thrombocytopenia (ITP) in patients (pts) affected by SARS-CoV2 have been reported. The management of COVID-19 in pts with simultaneous/previous ITP is challenging for the involvement of the haemostatic system. Aims : To describe the management and outcome of pts with ITP and COVID-19. Methods : Data were collected from clinical charts. All pts expressed their agreement. Results : 17 pts had RT-PCR confirmed SARS-CoV2 infection on a nasopharyngeal swab (October 2020-January 2021). Six pts were male (35.3%), 11 female (64.7%);median age 57 years (30-90). At the time of the infection, as regards ITP, pts were grouped as follows: 3 had simultaneous newly-diagnosed (ND) ITP (17.6%) and 1 experienced a relapse (5.8%) [median platelet count 5.5 × 109 /L (2-30 × 109 /L)];7 had chronic ITP on treatment (41.2%) (eltrombopag, n = 5;romiplostim, n = 1;prednisone, n = 1) and 2 had stable chronic ITP off-therapy (11.8%) [(median platelet count 63 × 109 /L (30-100 × 109 /L)];4 pts had a previous ITP (complete responders, CR) on follow-up (23.6%) (platelet count >100 × 109 /L). Only 2 pts had no COVID-related symptoms (11.8%). The most common symptoms were fever, anosmia, articular pain, mild-to-moderate respiratory distress. Three pts required hospitalization for acute platelet decrease and mucocutaneous bleeding (ND-ITP, n = 2;relapse, n = 1) and were responsive to intravenous dexamethasone (40 mg/ day, days 1-4) and immunoglobulins (1 g/kg) (17.6%). Three pts were hospitalized for pneumonia (ND-ITP, n = 1;chronic ITP, n = 1;CR, n = 1) and required antibiotics and oral corticosteroid (17.6%). Eleven pts recovered at home without bleeding;their platelet count did not show any change at the evaluation after quarantine (64.7%). All pts had seroconversion;no death occurred. Conclusions : ND-ITP triggered by COVID-19 is responsive to immunoglobulins and steroids. Outcome is favourable also for COVID-19 pts with off-therapy or on treatment ITP.

Immune thrombocytopenia during covid-19 pandemic: An italian monocentric experience

Background: Immune thrombocytopenia (ITP) is an acquired immune disorder characterised by a platelet count < 100x109/L, leading to an increased bleeding risk. Infectious diseases, especially from viral agents, may potentially cause ITP. Since the novel pandemic caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV2), known as COVID-19, has started in February 2020, different cases of ITP in patients affected by SARS-CoV2 have been reported. The management of COVID-19 in patients with simultaneous or previous ITP can be challenging because of the great involvement of the haemostatic system in this viral infection. Aims: To describe the management and outcome of patients with newly diagnosed (ND), chronic and previous ITP, infected by COVID-19. Methods: Data were collected from clinical charts and updated through telephone contacts. All patients expressed their agreement to participate to the study. Results: Seventeen patients had RT-PCR confirmed SARS-CoV2 infection on a nasopharyngeal swab (October 2020-January 2021). Six patients were male (35.3%) and 11 female (64.7%). The median age was 57 years (range 30-90). At the time of the COVID-19 infection, as regards ITP, patients were grouped as follows: 3 had simultaneous ND ITP (17.6%) and 1 experienced a relapse (5.8%) (median platelet count 5.5x109/L;range 2-30x109/L);7 had chronic ITP on treatment (41.2%) (eltrombopag, n=5;romiplostim, n=1;prednisone, n=1) and 2 patients had stable chronic ITP off-therapy (11.8%) (median platelet count 63x109/L;range 30-100x109/L);4 patients had a previous ITP on follow-up (FU) (23.6%) (platelet count >100x109/L). Fever, anosmia, dysgeusia, articular pain and mild-to-moderate respiratory distress were considered typically COVID19-related symptoms. Overall, 15 patients were symptomatic: 11 had only COVID19- related symptoms (64.8%), 1 presented with isolated mucocutaneous bleeding (5.8%) and 3 reported both (17.6%). Two patients did not refer any symptoms throughout the course of the infection (11.8%). Six cases required hospitalization (35.3%): 3 for acute decrease of platelet count and bleeding symptoms (17.6%) (ND ITP=2;ITP relapse=1);3 for pneumonia (17.6%) (ND ITP=1;chronic ITP on treatment=1;ITP on FU=1). Patients with bleeding symptoms were responsive to dexamethasone (40 mg/day, days 1-4) and immunoglobulins (1 g/kg). Patients with pneumonia were successfully treated with antibiotics and oral corticosteroids. The median duration of stay in the hospital was 10.5 days (range 3-20). Eleven patients recovered at home without any bleeding;they did not show any significant change in the platelet count at the first evaluation after quarantine (64.7%). Twelve patients had previously received either steroids (n=8) or steroid+splenectomy (n=4) (70.5%). Serious respiratory distress, requiring mechanic ventilation, was not recorded. Anti-thrombotic prophylaxis of COVID-related thromboembolism was not used and no cases of thrombosis were observed. The viral seroconversion was observed in all patients and no death occurred. Summary/Conclusion: In our experience, ND ITP triggered by COVID- 19 has been responsive to immunoglobulins and steroids. Overall outcome has been favourable also for COVID-19 patients with a stable off-therapy or on treatment ITP.

ITP World Impact Survey (I-WISh) 2.0: Further Exploration of the Impact of ITP on Patients

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder defined by a platelet count < 100 × 109/L without explanation, and an increased risk of bleeding. ITP itself as well as its treatments have multifaceted, often poorly understood impacts on patients’ quality of life (QoL). These effects include impact on activities of daily living, emotional health, energy, ability to think well and clearly, and productivity in the workplace. There are limited data on which individual aspects of ITP are perceived both by patients and physicians as having the greatest impact on QoL. Understanding patients’ perspectives is vital to optimize their QoL by specifying particular areas in need of therapy. I-WISh 1.0 was an exploratory, cross-sectional survey in which 1507 patients with ITP and 472 physicians across 13 countries completed separate, but related, online surveys that included assessments of ITP signs and symptoms, impact of symptoms, and patient-physician relationships. These findings have been presented at previous ASH and EHA congresses, and manuscripts are currently in preparation. However, although I-WISh 1.0 provided considerable insights into unexplored facets of the effects of ITP, an all-too-large number of gaps in understanding still remain. In response to this, I-WISh 2.0 is currently being developed. The objectives of the I-WISh 2.0 patient and physician cross-sectional surveys include: (1) to further explore the burden of fatigue and how it affects patients' lives, including what makes it better or worse;(2) to assess the emotional impact of living with chronic ITP, especially in relation to depression;(3) to assess how treatments for ITP can impact activities of daily living (positively and negatively);(4) to further relate effects of treatment to patients' QoL;and (5) to explore how telemedicine affects healthcare delivery for patients with ITP. Furthermore, data from subsets of patients will address (6) the impact of COVID-19 in patients with ITP;and (7) special issues affecting ITP in pregnancy. A steering committee of ITP expert physicians and patient advocacy group representatives are designing and will endorse the patient and physician surveys now nearing readiness after several meetings to determine the areas of greatest need of assessment. In addition, a control group will be included. Survey launch and data collection are scheduled to commence in early Q4 2020. Patients and physicians will complete similar online surveys. Both patient and physician surveys include a screener and sections of questions related to the specific objectives of I-WISh 2.0. The surveys include updates to key topics in I-WISh 1.0 (impact of fatigue, impact on daily life, treatment of ITP, emotional impact of ITP);validated patient-reported outcome tools to measure fatigue (MFIS-5), presence and severity of depression (PHQ-9), work-related burden (WPAI), and impact on quality of life (ILQI) tools;and questions related to COVID-19, telemedicine (remote patient monitoring), and pregnancy and ITP. Patients will be recruited to I-WISh 2.0 via treating physicians and patient advocacy groups, and will be included if they are ≥ 18 years of age, diagnosed with ITP, and agree to participate. Participating physicians will be required to be actively managing patients with ITP and have a minimum caseload of 3 ITP patients currently under their care;physicians must also have a primary specialty of hematology or hematology-oncology. Approval will be sought from an independent centralized Institutional Review Board. Data analysis will be primarily descriptive and correlative in nature. Breakdown by country and geographic areas will be included. A global sample is planned from 21 countries across 6 continents, with the aim of surveying more than 2000 patients and 600 physicians. I-WISh 2.0 will be the largest observational global survey ever conducted in ITP. If accepted, preliminary data are planned to be presented at the ASH meeting. I-WISh 2.0 will build on the strengths of I-WISh 1.0, which highlighted areas requir ng further assessment and will explore aspects of ITP of great interest that were neither conclusively addressed in the first survey nor well-studied in the past. Disclosures: Ghanima:Bristol Myers Squibb:Research Funding;Principia:Honoraria, Speakers Bureau;Pfizer:Honoraria, Research Funding, Speakers Bureau;Amgen:Honoraria, Speakers Bureau;Novartis:Honoraria, Speakers Bureau;Bayer:Research Funding.Provan:ONO Pharmaceutical:Consultancy;MedImmune:Consultancy;UCB:Consultancy;Amgen:Honoraria, Research Funding;Novartis:Honoraria, Research Funding.Cooper:Amgen:Honoraria, Speakers Bureau;Novartis:Honoraria, Speakers Bureau.Matzdorff:Roche Pharma AG:Other: Family stockownership;Amgen GmbH:Consultancy, Other: Honoraria paid to institution;Grifols Deutschland GmbH:Consultancy, Other: Honoraria paid to institution;Swedish Orphan Biovitrium GmbH:Consultancy, Other: Honoraria paid to institution;UCB Biopharma SRL:Consultancy, Other: Honoraria paid to institution;Novartis Oncology:Consultancy, Other: Honoraria paid to institution.Santoro:Novartis:Honoraria, Speakers Bureau;Takeda:Honoraria, Speakers Bureau;Amgen:Honoraria, Speakers Bureau;Novo Nordisk:Honoraria, Speakers Bureau;Bayer:Honoraria, Speakers Bureau;CSL Behring:Honoraria, Speakers Bureau;Roche:Honoraria, Speakers Bureau;Sobi:Honoraria, Speakers Bureau.Morgan:Sobi:Other: Consultancy fees paid to the ITP Support Association;UCB:Other: Consultancy fees paid to the ITP Support Association;Novartis:Other: Consultancy fees paid to the ITP Support Association.Kruse:Principia:Other: Grant paid to PDSA;Pfizer:Other: Grant and consultancy fee, all paid to PDSA;Argenx:Other: Grant paid to PDSA;Novartis:Other: PDSA received payment for recruiting patients to I-WISh and for promoting I-WISh on the globalitp.org website. Grant and consultancy fee, all paid to PDSA outside the submitted work;CSL Behring:Other: Grant paid to PDSA;UCB:Other: Grant and consultancy fee, all paid to PDSA;Rigel:Other: Grant paid to PDSA;Amgen:Other: Grant and honorarium, all paid to PDSA.Zaja:Janssen-Cilag:Honoraria, Speakers Bureau;Takeda:Honoraria, Speakers Bureau;Bristol Myers Squibb:Honoraria, Speakers Bureau;Grifols:Honoraria, Speakers Bureau;Amgen:Honoraria, Speakers Bureau;AbbVie:Honoraria, Speakers Bureau;Kyowa Kirin:Honoraria, Speakers Bureau;Mundipharma:Honoraria, Speakers Bureau;Novartis:Honoraria, Patents & Royalties: Pending patent (No. PAT058521) relating to TAPER trial (NCT03524612), Speakers Bureau;Roche:Honoraria, Speakers Bureau.Lahav:Novartis:Other: Consultancy fees paid to the Israeli ITP Support Association.Tomiyama:Novartis:Consultancy, Honoraria;Kyowa Kirin:Honoraria;Sysmex:Consultancy.Winograd:Novartis:Other: Consultancy fees paid to the Israeli ITP Support Association.Lovrencic:UCB:Other: Consultancy fees paid to AIPIT;Novartis:Other: Honorarium paid to AIPIT.Bailey:Adelphi Real World:Current Employment;Novartis:Other: Employee of Adelphi Real World, which has received consultancy fees from Novartis.Haenig:Novartis:Current Employment.Bussel:Novartis:Consultancy;Argenx:Consultancy;UCB:Consultancy;CSL Behring:Consultancy;Shionogi:Consultancy;Regeneron:Consultancy;3SBios:Consultancy;Dova:Consultancy;Principia:Consultancy;Rigel:Consultancy;Momenta:Consultancy;RallyBio:Consultancy;Amgen:Consultancy.

Peculiar clinical presentation of COVID-19 and predictors of mortality in the elderly: A multicentre retrospective cohort study.

BACKGROUND: The spectrum of COVID-19 clinical manifestations is not yet known. In the elderly, mortality and extrapulmonary involvement appears more frequent than expected. METHODS: A multicentre-retrospective-case-series study of COVID-19 patients, aged ≥65 years, hospitalised between March 1 and June 15, 2020. Patients were classified at admission into 3 groups based on their Clinical Frailty Scale (CFS) score: 1-3 (group A), 4-6 (group B) and 7-9 (group C). RESULTS: Of the 206 patients in the study, 60 (29%) were assigned to group A, 60 (29%) to B and 86 (42%) to C. Significantly more frequent in group C than in B or A were: mental confusion (respectively 65%, 33%, 7%; P < 0.001), kidney failure (39%, 22%, 20%; P = 0.019), dehydration syndrome (55%, 27%, 13%; P < 0.001), electrolyte imbalance (54%, 32%, 25%; P = 0.001), and diabetic decompensation (22%, 12%, 7%; P = 0.026). Crude mortality was 27%. By multivariate logistic regression model independent predictors of death were male sex (adjusted odds ratio (aOR) = 2.87,95%CI = 1.15-7.18), CFS 7-9 (aOR = 9.97,95%CI = 1.82-52.99), dehydration at admission (aOR = 4.27,95%CI = 1.72-10.57) and non-invasive/invasive ventilation (aOR = 4.88,95%CI = 1.94-12.26). CONCLUSIONS: Elderly patients with a high CFS showed frequent extrapulmonary signs at admission, even in the absence of lung involvement. These findings, along with a high CFS, predicted a significant risk of mortality.

Tocilizumab and corticosteroids for covid-19 treatment in elderly patients

Background. The mortality rate for coronavirus disease-19 (COVID-19) increases with age. Some anti-inflammatory drugs such as tocilizumab or steroids have been proposed for the treatment of severe disease;however, few data are available in the elderly. Methods. A retrospective case-series of patients hospitalized between March 1st and June 15th, 2020 with confirmed COVID-19 by RT-PCR testing on throat/nasopharyngeal swabs and age ≥ 65 years was analysed. Patients were retrospectively divided into three groups according to the chosen treatment [standard of care (SOC), tocilizumab or corticosteroids] and patient characteristics and occurrence of adverse events were compared among groups. Results. Overall, 206 patients were included, 148 treated with standard of care, 42 with steroids and 16 with tocilizumab. Patients treated with steroids or Tocilizumab presented more frequently with fever (p =.003), dyspnea (p <.001), bilateral opacities/infiltrates at chest X-ray (p =.026) or CT-scan (p =.020), and more frequently required non-invasive/invasive ventilation (p <.001). Crude mortality was 27%, without differences among groups (p =.074). No specific adverse events were observed during/after the administration of steroids or tocilizumab;however, a trend towards an increased risk of secondary infections was described compared to SOC (p =.097). At multivariate logistic regression, only tocilizumab administration was an independent predictor of secondary infections (aOR = 6.72, 95% CI = 1.43-31.39, p =.015). Conclusions. Tocilizumab and corticosteroid could have a possible role for severe form of pneumonia in course of COVID-19 also in elderly patients, even if great attention to the monitoring of infectious complications should be paid in this special population.