Infections in relapsed myeloma patients treated with isatuximab plus pomalidomide and dexamethasone during the COVID-19 pandemic: Initial results of a UK-wide real-world study.

OBJECTIVES: There are no real-world data describing infection morbidity in relapsed/refractory myeloma (RRMM) patients treated with anti-CD38 isatuximab in combination with pomalidomide and dexamethasone (IsaPomDex). In this UK-wide retrospective study, we set out to evaluate infections experienced by routine care patients who received this novel therapy across 24 cancer centres during the COVID-19 pandemic. METHODS: The primary endpoint was infection morbidity (incidence, grading, hospitalization) as well as infection-related deaths. Secondary outcomes were clinical predictors of increased incidence of any grade (G2-5) and high grade (≥G3) infections. RESULTS: In a total cohort of 107 patients who received a median (IQR) of 4 cycles (2-8), 23.4% of patients experienced ≥1 any grade (G2-5) infections (total of 31 episodes) and 18.7% of patients experienced ≥1 high grade (≥G3) infections (total of 22 episodes). Median time (IQR) from start of therapy to first episode was 29 days (16-75). Six patients experienced COVID-19 infection, of whom 5 were not vaccinated and 1 was fully vaccinated. The cumulative duration of infection-related hospitalizations was 159 days. The multivariate (MVA) Poisson Regression analysis demonstrated that a higher co-morbidity burden with Charlson Co-morbidity Index (CCI) score ≥4 (incidence rate ratio (IRR) = 3, p = 0.012) and sub-optimal myeloma response less than a partial response (

The influence of leprosy-related clinical and epidemiological variables in the occurrence and severity of COVID-19: A prospective real-world cohort study.

BACKGROUND: Protective effects of Bacillus Calmette-Guérin (BCG) vaccination and clofazimine and dapsone treatment against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. Patients at risk for leprosy represent an interesting model for assessing the effects of these therapies on the occurrence and severity of coronavirus disease 2019 (COVID-19). We assessed the influence of leprosy-related variables in the occurrence and severity of COVID-19. METHODOLOGY/PRINCIPAL FINDINGS: We performed a 14-month prospective real-world cohort study in which the main risk factor was 2 previous vaccinations with BCG and the main outcome was COVID-19 detection by reverse transcription polymerase chain reaction (RT-PCR). A Cox proportional hazards model was used. Among the 406 included patients, 113 were diagnosed with leprosy. During follow-up, 69 (16.99%) patients contracted COVID-19. Survival analysis showed that leprosy was associated with COVID-19 (p<0.001), but multivariate analysis showed that only COVID-19-positive household contacts (hazard ratio (HR) = 8.04; 95% CI = 4.93-13.11) and diabetes mellitus (HR = 2.06; 95% CI = 1.04-4.06) were significant risk factors for COVID-19. CONCLUSIONS/SIGNIFICANCE: Leprosy patients are vulnerable to COVID-19 because they have more frequent contact with SARS-CoV-2-infected patients, possibly due to social and economic limitations. Our model showed that the use of corticosteroids, thalidomide, pentoxifylline, clofazimine, or dapsone or BCG vaccination did not affect the occurrence or severity of COVID-19.

Repurposing of thalidomide and its derivatives for the treatment of SARS-coV-2 infections: Hints on molecular action.

AIMS: The SARS-coV-2 pandemic continues to cause an unprecedented global destabilization requiring urgent attention towards drug and vaccine development. Thalidomide, a drug with known anti-inflammatory and immunomodulatory effects has been indicated to be effective in treating a SARS-coV-2 pneumonia patient. Here, we study the possible mechanisms through which thalidomide might affect coronavirus disease-19 (COVID-19). METHODS: The present study explores the possibility of repurposing thalidomide for the treatment of SARS-coV-2 pneumonia by reanalysing transcriptomes of SARS-coV-2 infected tissues with thalidomide and lenalidomide induced transcriptomic changes in transformed lung and haematopoietic models as procured from databases, and further comparing them with the transcriptome of primary endothelial cells. RESULTS: Thalidomide and lenalidomide exhibited pleiotropic effects affecting a range of biological processes including inflammation, immune response, angiogenesis, MAPK signalling, NOD-like receptor signalling, Toll-like receptor signalling, leucocyte differentiation and innate immunity, the processes that are aberrantly regulated in severe COVID-19 patients. CONCLUSION: The present study indicates thalidomide analogues as a better fit for treating severe cases of novel viral infections, healing the damaged network by compensating the impairment caused by the COVID-19.

COVID-19 patients with psoriasis and psoriatic arthritis on biologic immunosuppressant therapy vs apremilast in North Spain.

Immunosuppressive and immunomodulatory treatments are critical for the management of inflammatory and autoimmune conditions such as psoriasis or psoriatic arthritis. Similar to those illnesses, the lung injury and acute respiratory distress shown in coronavirus disease 2019 (COVID-19) patients are the result of a disruption in the balance of pro- and anti-inflammatory cytokines. This hyperinflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), associated with the severity of the coronavirus disease, is called the cytokine storm. There is a growing concern regarding how patients on immunosuppressant biologic therapies might be at higher risk of being infected and whether they need to discontinue their treatment preemptively. Clinical data on COVID-19-infected patients with psoriasis or psoriatic arthritis are still scarce. Here, we presented seven cases of these type of patients. The patient infected with COVID-19 on apremilast and the one on apremilast with infected spouse showed the best safety profile and mildest symptoms. One of the secukinumab patients also presented a relatively good outcome. Infliximab patients and the one with serious comorbidities showed the worst outcome. Even though more clinical data are yet needed to draw strong conclusions, apremilast could be a safer alternative for dermatology and rheumatology patients in case of clinically important active infection.

Ixazomib-based frontline therapy in patients with newly diagnosed multiple myeloma in real-life practice showed comparable efficacy and safety profile with those reported in clinical trial: a multi-center study.

The induction therapy containing ixazomib, an oral proteasome inhibitor, has shown favorable efficacy and safety in clinical trials, but its experience in real-life remains limited. In routine practice, few patients received ixazomib-based induction therapy due to reasons including (1) patients' preference on oral regimens, (2) concerns on adverse events (AEs) of other intravenous/subcutaneous regimens, (3) requirements for less center visits, and (4) fears of COVID-19 and other infectious disease exposures. With the aim of assessing the real-life effectiveness and safety of ixazomib-based induction therapy, we performed this multi-center, observational study on 85 newly diagnosed multiple myeloma (NDMM) patients from 14 medical centers. Ixazomib-based regimens included ixazomib-lenalidomide-dexamethasone (IRd) in 44.7% of patients, ixazomib-dexamethasone (Id) in 29.4%, and Id plus another agent (doxorubicin, cyclophosphamide, thalidomide, or daratumumab) in 25.9%. Different ixazomib-based therapies were applied due to (1) financial burdens or limitations on local health insurance coverage, (2) concerns on treatment tolerance, and (3) drug accessibility issue. Ten patients received ixazomib maintenance. The median age was 67 years; 43.5% had ISS stage III disease; 48.2% had an Eastern Cooperative Oncology Group performance score ≥ 2; and 17.6% with high-risk cytogenetic abnormalities. Overall response rate for all 85 patients was 95.3%, including 65.9% very good partial response or better and 29.5% complete responses. The median time to response was 30 days. The response rate was similar across different ixazomib-based regimens. Median progression-free survival was not reached. Severe AEs (≥ grade 3) were reported in 29.4% of patients. No grade 3/4 peripheral neuropathy (PN) occurred. Patients received a median of 6 (range 1-20) cycles of ixazomib treatment; 56.6% remained on treatment at data cutoff; 15.3% discontinued treatment due to intolerable AEs. These results support that the ixazomib-based frontline therapy was highly effective with acceptable toxicity in routine practice and the ixazomib oral regimens could be good alternative options for NDMM patients.

Can roflumilast become steroid-sparing alternative in the treatment of COVID-19?

According to WHO the worst of the COVID-19 pandemic is yet to come. Despite of the exceptional measures being undertaken by regulatory agencies to expedite vaccine development, we may be several months if not years away from an effective vaccine. In such unprecedented times, the only resort nations have at their disposal is to identify and repurpose existing drugs against COVID-19 based on their known clinical or pharmacological profile which can provide direct or corroborative evidence of favorable benefit: risk in the management of COVID-19. Immune-mediated inflammation remains the hallmark of severe complications related to COVID-19 and while corticosteroids have shown preliminary evidence of benefit, they can act like a double-edged sword for majority of COVID-19 patients. Therefore, there is a need to identify 'non-steroid' potent and safe anti-inflammatory agents for use in therapeutic armamentarium against COVID-19. This article makes a case for one such existing drug, roflumilast, that can emerge as a steroid-sparing alternative against COVID-19.

Outcome of COVID-19 in multiple myeloma patients in relation to treatment.

COVID-19 has emerged as a global pandemic. Cancer patients have been reported to be at higher risk for adverse outcome of COVID-19. Studies are ongoing to decipher the risk factors and risk groups among cancer patients as well as strategies to refine treatment approaches. Here, we report eight patients with multiple myeloma that underwent immunomodulatory therapies with daratumumab or lenalidomide-based combination treatments and one patient with smoldering multiple myeloma, all of which presented with symptomatic COVID-19. We report that patients that succumbed to COVID-19 presented with either progressive tumor disease under daratumumab treatment or were in remission under lenalidomide-dexamethasone treatment.

Alternative management of Covid-19 infection.

Cytokine storm is a life-threatening complication of Covid-19 infection. Excessive cytokines are the products of hyperactive immune inflammatory response mounted by the host against the virus. There is no agreed treatment for cytokine storm. Three therapeutic agents with proven immune-modulatory properties in regular use in a wide range of inflammatory disorders (high dose intravenous immunoglobulin, Rituximab and thalidomide) are proposed for the treatment of cytokine storm. Safety and efficacy of the proposed treatment should be assessed by randomised controlled clinical trials. The use of the proposed treatment is expected to reduce the mortality rate and alter the overall management of the pandemic.