Despite lower virulence, the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) still poses a relevant threat for immunocompromised patients. A retrospective multicentric study was conducted to evaluate the efficacy of pre-exposure prophylaxis with tixagevimab/cilgavimab (Evusheld) with a 6-month follow-up for preventing severe COVID-19 in adult patients with hematology malignancy. Among the 606 patients in the cohort, 96 (16%) contracted COVID-19 with a median of 98.5 days after Evusheld administration. A total of 75% of patients had asymptomatic or mild severity of COVID-19, while just 25% of patients with SARS-CoV-2 positivity had to be hospitalized. Two patients (2%) died directly, and one patient (1%) in association with COVID-19. Eight patients (1.3%) of every cohort experienced adverse events related to Evusheld, mostly grade 1 and of reversible character. It was found that complete vaccination status or positive seroconversion was not associated with lower risk of COVID-19 infection. Previous treatment with an anti-CD20 monoclonal antibody was associated with higher rates of COVID-19, while previous treatment with anti-CD38 monoclonal antibody was not, as was the case for recipients of hematopoietic stem cell transplantation or CAR-T cell therapy. Presence of other comorbidities was not associated with more severe COVID-19. The results support the growing evidence for Evusheld's efficacy against severe COVID-19 in patients with hematology malignancies.
- MeSH
- COVID-19 * MeSH
- dospělí MeSH
- hematologické nádory * komplikace farmakoterapie epidemiologie MeSH
- lidé MeSH
- monoklonální protilátky MeSH
- preexpoziční profylaxe * MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Česká republika MeSH
- MeSH
- COVID-19 * mortalita komplikace MeSH
- dexamethason * terapeutické užití MeSH
- dospělí MeSH
- farmakoterapie COVID-19 * MeSH
- hematologické nádory * mortalita farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- registrace * MeSH
- SARS-CoV-2 * izolace a purifikace MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. METHODS: Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. RESULTS: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death. CONCLUSIONS: Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy.
- MeSH
- antivirové látky terapeutické užití MeSH
- COVID-19 * MeSH
- farmakoterapie COVID-19 MeSH
- hematologické nádory * komplikace farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- ritonavir terapeutické užití MeSH
- SARS-CoV-2 MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
The protein cereblon (CRBN) is a substrate receptor of the cullin 4-really interesting new gene (RING) E3 ubiquitin ligase complex CRL4CRBN. Targeting CRBN mediates selective protein ubiquitination and subsequent degradation via the proteasome. This review describes novel thalidomide analogs, immunomodulatory drugs, also known as CRBN E3 ubiquitin ligase modulators or molecular glues (avadomide, iberdomide, CC-885, CC-90009, BTX-1188, CC-92480, CC-99282, CFT7455, and CC-91633), and CRBN-based proteolysis targeting chimeras (PROTACs) with increased efficacy and potent activity for application in hematologic malignancies. Both types of CRBN-binding drugs, molecular glues, and PROTACs stimulate the interaction between CRBN and its neosubstrates, recruiting target disease-promoting proteins and the E3 ubiquitin ligase CRL4CRBN. Proteins that are traditionally difficult to target (transcription factors and oncoproteins) can be polyubiquitinated and degraded in this way. The competition of CRBN neosubstrates with endogenous CRBN-interacting proteins and the pharmacology and rational combination therapies of and mechanisms of resistance to CRL4CRBN modulators or CRBN-based PROTACs are described.
- MeSH
- hematologické nádory * farmakoterapie MeSH
- lidé MeSH
- proteasy * chemie genetika metabolismus MeSH
- transkripční faktory metabolismus MeSH
- ubikvitinace MeSH
- ubikvitinligasy chemie genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- MeSH
- antitumorózní látky škodlivé účinky MeSH
- chronická myeloidní leukemie epidemiologie farmakoterapie MeSH
- hematologické nádory * epidemiologie farmakoterapie klasifikace MeSH
- inhibitory tyrosinkinasy škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- mnohočetný myelom epidemiologie farmakoterapie prevence a kontrola MeSH
- nežádoucí účinky léčiv klasifikace MeSH
- terciární prevence MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- buněčná a tkáňová terapie * metody MeSH
- hematologické nádory * farmakoterapie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
It has been recommended that patients with leukaemias and lymphomas undergo universal screening for SARS-COV-2 using RT-qPCR before each treatment on the grounds of their high risk of experiencing severe forms of COVID-19. This raises a conflict with different recommendations which prioritise testing symptomatic patients. We found that among 56 RT-qPCR obtained in asymptomatic patients with hematologic neoplasms before chemotherapy administration, 2 (3.5%) were positive. A negative result did not exclude SARS-COV-2 infection in 1 patient (1.8%). It is unclear what the benefit of screening for SARS-COV-2 using RT-qPCR in patients with hematologic neoplasms who receive chemotherapy is.
- MeSH
- COVID-19 * diagnóza MeSH
- hematologické nádory * diagnóza farmakoterapie genetika MeSH
- leukemie * MeSH
- lidé MeSH
- SARS-CoV-2 MeSH
- senzitivita a specificita MeSH
- testování na COVID-19 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- antitumorózní látky farmakologie terapeutické užití MeSH
- diferenciální diagnóza MeSH
- hematologické nádory * diagnóza farmakoterapie terapie MeSH
- individualizovaná medicína metody MeSH
- leukemie diagnóza farmakoterapie terapie MeSH
- lidé MeSH
- lymfom diagnóza terapie MeSH
- příznaky a symptomy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
