Multi-omics analysis identifies repurposing bortezomib in the treatment of kidney-, nervous system-, and hematological cancers.

Repurposing of FDA-approved drugs is a quick and cost-effective alternative to de novo drug development. Here, we identify genes involved in bortezomib sensitivity, predict cancer types that may benefit from treatment with bortezomib, and evaluate the mechanism-of-action of bortezomib in breast cancer (BT-474 and ZR-75-30), melanoma (A-375), and glioblastoma (A-172) cells in vitro. Cancer cell lines derived from cancers of the blood, kidney, nervous system, and skin were found to be significantly more sensitive to bortezomib than other organ systems. The in vitro studies confirmed that although bortezomib effectively inhibited the ß5 catalytic site in all four cell lines, cell cycle arrest was only induced in G2/M phase and apoptosis in A-375 and A-172 after 24h. The genomic and transcriptomic analyses identified 33 genes (e.g. ALDH18A1, ATAD2) associated with bortezomib resistance. Taken together, we identified biomarkers predictive of bortezomib sensitivity and cancer types that might benefit from treatment with bortezomib.

Effectiveness of the antiviral medications azvudine and nirmatrelvir-ritonavir in treating COVID-19 in patients with hematological malignancies.

BACKGROUND: Patients with Hematological Malignancies (HM) are at a high risk of mortality from Coronavirus disease 2019 (COVID-19). The available antivirals were different between China and other countries. In China, azvudine was obtained for emergency use to treat adult COVID-19 patients with moderate symptoms in July 2022. While nirmatrelvir-ritonavir was well-known and used in many countries. The purpose of the present study was to assess whether there was any difference in the efficacy and safety of the two drugs. METHODS: This study was a prospective observational study of patients with HM who developed COVID-19. Patients were divided into three treatment groups: nirmatrelvir-ritonavir, azvudine, and observation. Treatment outcomes, first nucleic acid test negative time, hospitalization time, and the conversion rate of mild or moderate disease to severe disease were recorded. RESULTS: First nucleic acid test negative time (23.5 days vs. 34 days, p = 0.015), hospitalization time (p = 0.015), and conversion rate (31.8 % vs. 8 %, p = 0.046) were statistically different between the nirmatrelvir-ritonavir and observation groups. First nucleic acid test negative time (20 days vs. 34 days, p = 0.009) and hospitalization time (p = 0.026) were statistically different between the azvudine and observation groups. ECOG score and liver disease were significantly associated with the conversion rate from mild or moderate disease to severe disease using multivariate analysis (p < 0.05). CONCLUSIONS: The authors found no significant differences existed in outcome measures between patients with HM and COVID-19 who were treated with nirmatrelvir-ritonavir or azvudine.

Vitamin C Supplementation in the Treatment of Autoimmune and Onco-Hematological Diseases: From Prophylaxis to Adjuvant Therapy.

Vitamin C is a water-soluble vitamin introduced through the diet with anti-inflammatory, immunoregulatory, and antioxidant activities. Today, this vitamin is integrated into the treatment of many inflammatory pathologies. However, there is increasing evidence of possible use in treating autoimmune and neoplastic diseases. We reviewed the literature to delve deeper into the rationale for using vitamin C in treating this type of pathology. There is much evidence in the literature regarding the beneficial effects of vitamin C supplementation for treating autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) and neoplasms, particularly hematological neoplastic diseases. Vitamin C integration regulates the cytokines microenvironment, modulates immune response to autoantigens and cancer cells, and regulates oxidative stress. Moreover, integration therapy has an enhanced effect on chemotherapies, ionizing radiation, and target therapy used in treating hematological neoplasm. In the future, integrative therapy will have an increasingly important role in preventing pathologies and as an adjuvant to standard treatments.

Update of antibody-drug conjugates for hematological malignancies.

PURPOSE OF REVIEW: Antibody-drug conjugates (ADCs), consisting of monoclonal antibodies (mAbs) covalently linked to cytotoxic drugs via chemical linkers, are a kind of promising tumor immunotherapy. ADCs also face a number of challenges, including unavoidable adverse effects, drug resistance, tumor targeting and payload release. To address these issues, in addition to optimizing the individual components of ADCs, such as new payloads, linkage sites and new targets, and using bispecific antibodies to increase precision, attention should be paid to optimizing the dosage of ADCs. RECENT FINDINGS: There are currently 7 ADCs approved for marketing by the Food and Drug Administration (FDA) for hematological malignancies, and dozens of other ADCs are either in clinical trials or in the process of applying for marketing. In recent clinical studies targeting ADCs in hematologic malignancies, in addition to validating effectiveness in different indications, researchers have attempted to combine ADCs with other chemotherapeutic agents in anticipation of increased therapeutic efficacy. Furthermore, the availability of bispecific antibodies may increase the safety and efficacy of ADCs. SUMMARY: This review summarized the progress of research on ADCs in hematological malignancies, the challenges being faced, and possible future directions to improve the efficacy of ADCs, which can provide novel insight into the future exploration of ADCs in the treatment of hematological malignancies.

The role of signaling lymphocyte activation molecule family receptors in hematologic malignancies.

PURPOSE OF REVIEW: In this review, we provide an overview of the current understanding of SLAM-family receptors in hematologic malignancies. We highlighted their contribution to the disease pathogenesis and targeting strategies to improve therapeutic outcomes. RECENT FINDINGS: Emerging studies have reported the tumor-promoting role of SLAM-family receptors in various hematologic malignancies, including chronic lymphocytic leukemia, acute myeloid leukemia, and multiple myeloma. Specifically, they regulate the interaction between malignant cells and the tumor microenvironment to promote apoptosis resistance, therapeutic resistance, impairment of antitumor and tumor progression. SUMMARY: SLAM-family receptors promote the progression of hematologic malignancies by regulating the interaction between malignant cells and the tumor microenvironment. This provides the rationale that SLAM-targeted therapies are appealing strategies to enhance therapeutic outcomes in patients.

Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments.

In this editorial, we discussed the apparent discrepancy between the findings described by Colapietro et al, in their case report and data found in the literature. Colapietro et al reported a case of hepatitis B virus (HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton's tyrosine kinase (BTK) inhibitor therapy. First of all, we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response, focusing our attention on the protective role of anti-HBs. We then carefully analyzed literature data on the risk of HBV reactivation (HBVr) in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies. Based on literature data, we suggested that several factors may contribute to the different risks of HBVr: The type of hematologic malignancy; the type of therapy (BTK inhibitors, especially second-generation, seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors); previous exposure to an anti-CD20 as first-line therapy; and ethnicity and HBV genotype. Therefore, the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

Development and validation of an LC-MS/MS method for ruxolitinib quantification: advancing personalized therapy in hematologic malignancies.

Background: Hematologic malignancies such as leukemia and lymphoma present treatment challenges due to their genetic and molecular heterogeneity. Ruxolitinib, a Janus kinase (JAK) inhibitor, has demonstrated efficacy in managing these cancers. However, optimal therapeutic outcomes are contingent upon maintaining drug levels within a therapeutic window, highlighting the necessity for precise drug monitoring. Methods: We developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify ruxolitinib in human plasma, improving upon traditional methods in specificity, sensitivity, and efficiency. The process involved the use of advanced chromatographic techniques and robust mass spectrometric conditions to ensure high accuracy and minimal matrix effects. The study was conducted using samples from 20 patients undergoing treatment, with calibration standards ranging from 10 to 2000 ng/mL. Results: The method displayed linearity (R 2 > 0.99) across the studied range and proved highly selective with no significant interference observed. The method's precision and accuracy met FDA guidelines, with recovery rates consistently exceeding 85%. Clinical application demonstrated significant variability in ruxolitinib plasma levels among patients, reinforcing the need for individualized dosing schedules. Conclusion: The validated LC-MS/MS method offers a reliable and efficient tool for the therapeutic drug monitoring of ruxolitinib, facilitating personalized treatment approaches in hematologic malignancies. This approach promises to enhance patient outcomes by optimizing dosing to reduce toxicity and improve efficacy.

Discovery of a Highly Potent and Selective BRD9 PROTAC Degrader Based on E3 Binder Investigation for the Treatment of Hematological Tumors.

BRD9 is a pivotal epigenetic factor involved in cancers and inflammatory diseases. Still, the limited selectivity and poor phenotypic activity of targeted agents make it an atypically undruggable target. PROTAC offers an alternative strategy for overcoming the issue. In this study, we explored diverse E3 ligase ligands for the contribution of BRD9 PROTAC degradation. Through molecular docking, binding affinity analysis, and structure-activity relationship study, we identified a highly potent PROTAC E5, with excellent BRD9 degradation (DC50 = 16 pM) and antiproliferation in MV4-11 cells (IC50 = 0.27 nM) and OCI-LY10 cells (IC50 = 1.04 nM). E5 can selectively degrade BRD9 and induce cell cycle arrest and apoptosis. Moreover, the therapeutic efficacy of E5 was confirmed in xenograft tumor models, accompanied by further RNA-seq analysis. Therefore, these results may pave the way and provide the reference for the discovery and investigation of highly effective PROTAC degraders.

PIM kinase inhibitors: an updated patent review (2016-present).

INTRODUCTION: PIM Kinases (PIM-1, PIM-2, and PIM-3) have been reported to play crucial role in signaling cascades that govern cell survival, proliferation, and differentiation. Over-expression of these kinases leads to hematological malignancies such as diffuse large B cell lymphomas (DLBCL), multiple myeloma, leukemia, lymphoma and prostate cancer etc. PIM kinases as biomarkers and potential therapeutic targets have shown promise toward precision cancer therapy. The selective PIM-1, PIM-2, and/or PIM-3 isoform inhibitors have shown significant results in patients with advanced stages of cancer including relapsed/refractory cancer. AREAS COVERED: A comprehensive literature review of PIM Kinases (PIM-1, PIM-2, and PIM-3) in oncogenesis, the patented PIM kinase inhibitors (2016-Present), and their pharmacological and structural insights have been highlighted. EXPERT OPINION: Recently, PIM kinases viz. PIM-1, PIM-2, and PIM-3 (members of the serine/threonine protein kinase family) as therapeutic targets have attracted considerable interest in oncology especially in hematological malignancies. The patented PIM kinase inhibitors comprised of heterocyclic (fused)ring structure(s) like indole, pyridine, pyrazine, pyrazole, pyridazine, piperazine, thiazole, oxadiazole, quinoline, triazolo-pyridine, pyrazolo-pyridine, imidazo-pyridazine, oxadiazole-thione, pyrazolo-pyrimidine, triazolo-pyridazine, imidazo-pyridazine, pyrazolo-quinazoline and pyrazolo-pyridine etc. showed promising results in cancer chemotherapy.

Metformin as a therapeutic tool for resistant hematological malignancies: a literature review.

BACKGROUND AND OBJECTIVE: Hematological malignancies (HMs) are a group of neoplasms with hematopoietic origin, currently divided into leukemias, lymphomas and multiple myeloma (MM). Although the advances in the management of HMs, the rate of drug resistance, relapse and refractory disease has been increasing, requiring new therapeutic strategies. In this review, we aim to summarize metformin's antitumoral mechanisms of action and present the latest studies of metformin action in HMs, including in resistant ones. METHODS: For this review of literature, studies published between 1996 and 2023 from PubMed and clinical trials submitted to clinicaltrials.gov were considered. KEY CONTENT AND FINDINGS: Throughout this review we demonstrated the capacity of metformin to act as an anti-HMs drug, being able to re-sensitize HMs to classical anti-HMs agents and to overcome relapse and refractory HMs, as shown in vitro and in vivo studies. Associated with the potential anti-HM effect of metformin, some clinical trials are in progress, including in the view of reducing resistance and recurrence rate of HMs, which requires further exploration. The relationship among HMs cancer stem cells (HMs CSCs), drug resistance, cancer recurrence, and the effect of metformin in inhibiting CSCs were also discussed, despite this field needing more attention. CONCLUSIONS: In summary, metformin is a promising anti-HMs drug that can enhance patients' survival and prognosis through its action in the improvement of HMs response.

Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo.

Background: Chimeric antigen receptor T (CAR-T) cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies. However, there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T (CAR-T) cell therapy, as well as the optimal timing for CAR-T cell infusion post-chemotherapy. Materials and Methods: We employed cell-derived tumor xenograft (CDX) murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment. Furthermore, transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen. Results: Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine, followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy, exerts the most efficacious therapeutic effect in B-cell hematological malignancies. Concurrently, RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism, primarily through the inhibition of key mitochondrial targets, such as C-Jun Kinase enzyme (C-JUN). Conclusion: In summary, the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

Population Pharmacokinetic Models of Venetoclax in Hematologic Malignancies: A Systematic Review.

Several population pharmacokinetic (PPK) models of B cell lymphoma-2 (BCL-2) venetoclax (VEN) have been developed and published to characterize the influencing factors of pharmacokinetics in hematologic malignancies. This review described PPK models of VEN examining the magnitude and types of covariate effects in PK parameters, as well as identified areas that require further investigation in order to facilitate their use. Currently, there are six analyses on PPK models of VEN summarized in this review. Most analyses described the pharmacokinetics of VEN with a two-compartment model and all covariates are categorical. The median estimated apparent clearance (CL/F) was 446 L/Day and apparent volume of distribution of the central compartment (V2/F) was 114.5 L. The median IIV of CL/F reported was 39.5% and V2/F was 46.7%. Most commonly, CYP3A inhibitors, OATP1B3 inhibitors and rituximab co-administration were found to be significant covariates on CL/F. In addition, sex and population were influential covariates on V2/F. A detailed description of the characteristics of PPK models of VEN is provided in this review, as well as the effects of covariates on the PK parameters. For future development of the VEN PPK model, CYP3A inhibitors, rituximab co-administration, OATP1B1 transporter inhibitors, sex, population, and food might be considered. Further research and comprehensive investigations should be undertaken to explore reference ranges for therapeutic drug monitoring, define the potential role of patients with cerebrospinal fluid complications, and assess new or potential covariates. These endeavors will facilitate the development of personalized VEN therapy.

Determination of a vancomycin nephrotoxicity threshold and assessment of target attainment in hematology patients.

An area-under-the-curve (AUC24)-based approach is recommended to guide vancomycin therapeutic drug monitoring (TDM), yet trough concentrations are still commonly used despite associated risks. A definitive toxicity target is lacking, which is important for hematology patients who have a higher risk of nephrotoxicity. The aims were to (1) assess the impact of trough-based TDM on acute kidney injury (AKI) incidence, (2) establish a vancomycin nephrotoxicity threshold, and (3) evaluate the proportion of hematology patients achieving vancomycin therapeutic targets. Retrospective data was collected from 100 adult patients with a hematological malignancy or aplastic anemia who received vancomycin between April 2020 and January 2021. AKI occurrence was determined based on serum creatinine concentrations, and individual pharmacokinetic parameters were estimated using a Bayesian approach. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pharmacokinetic indices to predict AKI occurrence. The proportion of patients who achieved target vancomycin exposure was evaluated based on an AUC24/MIC ≥400 and the determined toxicity threshold. The incidence of AKI was 37%. ROC curve analysis indicated a maximum AUC24 of 644 mg.h/L over the treatment period was an important predictor of AKI. By Day 4 of treatment, 29% of treatment courses had supratherapeutic vancomycin exposure, with only 62% of courses achieving AUC24 targets. The identified toxicity threshold supports an AUC24 target range of 400-650 mg.h/L, assuming an MIC of 1 mg/L, to optimize vancomycin efficacy and minimize toxicity. This study highlights high rates of AKI in this population and emphasizes the importance of transitioning from trough-based TDM to an AUC-based approach to improve clinical outcomes.

Navigating the complex terrain of hepatitis B virus reactivation in the era of Bruton tyrosine kinase inhibitors.

In this editorial, we offer a summary of the risk associated with hepatitis B reactivation (HBVr) in the setting of both solid and hematologic malignancies treated with Bruton tyrosine kinase (BTK) inhibitors, with insights derived from current studies. Furthermore, we emphasize the critical need for a framework regarding robust risk evaluation in patients undergoing such treatments. This framework is essential for identifying those at increased risk of HBVr, enabling healthcare providers to implement proactive measures to prevent reactivation and ensure the safe administration of BTK inhibitor therapy.

High mortality associated with inappropriate initial antibiotic therapy in hematological malignancies with Klebsiella pneumoniae bloodstream infections.

Bloodstream infections caused by multidrug-resistant organisms such as Klebsiella pneumoniae are a significant challenge in managing hematological malignancies. This study aims to characterize the epidemiology of Klebsiella pneumoniae bloodstream infections specifically in patients with hematological malignancies, delineate the patterns of initial antibiotic therapy, assess the prevalence of resistant strains, identify risk factors for these resistant strains, and evaluate factors influencing patient outcomes. A retrospective analysis was conducted at a single center from January 2017 to December 2020, focusing on 182 patients with hematological malignancies who developed Klebsiella pneumoniae bloodstream infections. We compared the 30-day mortality rates between patients receiving appropriate and inappropriate antibiotic treatments, including the effectiveness of both single-drug and combination therapies. Kaplan-Meier survival analysis and multivariate logistic and Cox regression were used to identify factors influencing mortality risk. The 30-day all-cause mortality rate was 30.2% for all patients. The 30-day all-cause mortality rates were 77.2% and 8.8% in patients who received inappropriate initial treatment and appropriate initial treatment (p < 0.001). Inappropriate initial treatment significantly influenced mortality and was a key predictor of 30-day mortality, along with septic shock and previous intensive care unit (ICU) stays. Patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections exhibited more severe clinical symptoms compared to the CSKP group. The study demonstrates a significant association between empirical carbapenem administration and the escalating prevalence of CRKP and multidrug-resistant K. pneumoniae (MDR-KP) infections. Furthermore, the study identified inappropriate initial antibiotic therapy, septic shock, and ICU admission as independent risk factors for 30-day mortality.

Revisiting intrathecal thiotepa: Efficacy and safety in secondary CNS malignancies.

Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal (IT) drug administration into the cerebrospinal fluid (CSF) is a strategy to overcome this problem. Thiotepa has effective CNS penetration but its popularity has waned over the last two decades due to concerns about its efficacy and potential systemic toxicity. This review evaluates the available evidence for the use of IT thiotepa in hematologic malignancies and non-CNS solid tumors with leptomeningeal disease metastases (LMD). Our search shows that IT thiotepa is a reasonable alternative in hematologic malignancies and LMD due to solid organ malignancies. This suggests a potential role of IT thiotepa in second-or third-line treatment or a substitute role in cases of drug-shortages and adverse effects with other agents. Future research should focus on rigorous comparative trials to establish its definitive role in the evolving landscape of CNS-directed chemotherapy.

A real-world pharmacovigilance study on cardiovascular adverse events of tisagenlecleucel using machine learning approach.

Chimeric antigen receptor T-cell (CAR-T) therapies are a paradigm-shifting therapeutic in patients with hematological malignancies. However, some concerns remain that they may cause serious cardiovascular adverse events (AEs), for which data are scarce. In this study, gradient boosting machine algorithm-based model was fitted to identify safety signals of serious cardiovascular AEs reported for tisagenlecleucel in the World Health Organization Vigibase up until February 2024. Input dataset, comprised of positive and negative controls of tisagenlecleucel based on its labeling information and literature search, was used to train the model. Then, we implemented the model to calculate the predicted probability of serious cardiovascular AEs defined by preferred terms included in the important medical event list from European Medicine Agency. There were 467 distinct AEs from 3,280 safety cases reports for tisagenlecleucel, of which 363 (77.7%) were classified as positive controls, 66 (14.2%) as negative controls, and 37 (7.9%) as unknown AEs. The prediction model had area under the receiver operating characteristic curve of 0.76 in the test dataset application. Of the unknown AEs, six cardiovascular AEs were predicted as the safety signals: bradycardia (predicted probability 0.99), pleural effusion (0.98), pulseless electrical activity (0.89), cardiotoxicity (0.83), cardio-respiratory arrest (0.69), and acute myocardial infarction (0.58). Our findings underscore vigilant monitoring of acute cardiotoxicities with tisagenlecleucel therapy.

Targeting hematological malignancies with isoxazole derivatives.

Compounds with a heterocyclic isoxazole ring are well known for their diverse biologic activities encompassing antimicrobial, antipsychotic, immunosuppressive, antidiabetic and anticancer effects. Recent studies on hematological malignancies have also shown that some of the isoxazole-derived compounds feature encouraging cancer selectivity, low toxicity to normal cells and ability to overcome cancer drug resistance of conventional treatments. These characteristics are particularly promising because patients with hematological malignancies face poor clinical outcomes caused by cancer drug resistance or relapse of the disease. This review summarizes the knowledge on isoxazole-derived compounds toward hematological malignancies and provides clues on their mechanism(s) of action (apoptosis, cell cycle arrest, ROS production) and putative pharmacological targets (c-Myc, BET, ATR, FLT3, HSP90, CARM1, tubulin, PD-1/PD-L1, HDACs) wherever known.

MEG3 in hematologic malignancies: from the role of disease biomarker to therapeutic target.

Maternally expressed gene 3 ( MEG3 ) is a noncoding RNA that is known as a tumor suppressor in solid cancers. Recently, a line of studies has emphasized its potential role in hematological malignancies in terms of tumorigenesis, metastasis, and drug resistance. Similar to solid cancers, MEG3 can regulate various cancer hallmarks via sponging miRNA, transcriptional, or posttranslational regulation mechanisms, but may regulate different key elements. In contrast with solid cancers, in some subtypes of leukemia, MEG3 has been found to be upregulated and oncogenic. In this review, we systematically describe the role and underlying mechanisms of MEG3 in multiple types of hematological malignancies. Particularly, we highlight the role of MEG3 in drug resistance and as a novel therapeutic target.

Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment.

OBJECTIVE: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies. DESIGN: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies. RESULTS: Patients with a history of anti-CD20 therapies showed a prolonged time-to-negative RT-PCR for SARS-CoV-2 infection compared to non-treated patients (33 d (28;75) vs 15 (11;25); p = .002). Similar results were observed in patients with solid tumours in comparison to those with haematological malignancies (13 (10;16) vs 26 (17;50); p < .001). No serious adverse events were documented. CONCLUSIONS: Patients with haematological malignancies appear to be at a heightened risk for delayed SARS-CoV-2 clearance and subsequent clinical complications. These findings support plitidepsin as a well-tolerated treatment in this high-risk group. A phase II clinical trial (NCT05705167) is ongoing to evaluate plitidepsin as an antiviral drug in this population.KEY POINTSHaematological patients face an increased risk for severe COVID-19.Anti-CD20 therapies could increase fatal outcomes in COVID-19 patients.Persistent viral replication is increased in immunocompromised patients.Plitidepsin does not lead to new serious adverse events in immunocompromised patients.