May Ibrutinib Have Activity in Respiratory Complications by SARS-CoV-2? Clinical Experience in a Patient with Chronic Lymphocytic Leukemia

Molina‐Cerrillo, Javier; Marquet-Palomanes, Juan; Alonso‐Gordoa, Teresa; López‐Jiménez, Javier; Grande, Enrique

doi:10.3390/healthcare9010078

Cited by 5 publications

(5 citation statements)

References 13 publications

(11 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acalabrutinib treatment similarly ameliorates LPS/galactosamine-induced infiltration of macrophages and reduces serum levels of MCP-1 in a mouse model of hepatic damage by inhibiting TLR4-induced NF-κB activation (Shaker et al, 2020). Interestingly, a number of case studies have reported the effects of ibrutinib or acalabrutinib on attenuating inflammatory cytokine and chemokine release, lung injury and respiratory failure in patients with severe COVID-19 (Lin et al, 2020;Rada et al, 2020;Scarfo et al, 2020;Treon et al, 2020;Alsuliman et al, 2021;Benner and Carson, 2021;Fiorcari et al, 2021;Molina-Cerrillo et al, 2021). Specifically, Roschewski et al (2020) found that acalabrutinib treatment improves oxygenation and reduces IL-6 production in monocytes of patients with severe COVID-19.…”

Section: Monocytes and Macrophagesmentioning

confidence: 99%

Multifaceted Immunomodulatory Effects of the BTK Inhibitors Ibrutinib and Acalabrutinib on Different Immune Cell Subsets – Beyond B Lymphocytes

Zhu

Gokhale

Jung

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The clinical success of the two BTK inhibitors, ibrutinib and acalabrutinib, represents a major breakthrough in the treatment of chronic lymphocytic leukemia (CLL) and has also revolutionized the treatment options for other B cell malignancies. Increasing evidence indicates that in addition to their direct effects on B lymphocytes, both BTK inhibitors also directly impact the homeostasis, phenotype and function of many other cell subsets of the immune system, which contribute to their high efficacy as well as adverse effects observed in CLL patients. In this review, we attempt to provide an overview on the overlapping and differential effects of ibrutinib and acalabrutinib on specific receptor signaling pathways in different immune cell subsets other than B cells, including T cells, NK cells, monocytes, macrophages, granulocytes, myeloid-derived suppressor cells, dendritic cells, osteoclasts, mast cells and platelets. The shared and distinct effects of ibrutinib versus acalabrutinib are mediated through BTK-dependent and BTK-independent mechanisms, respectively. Such immunomodulatory effects of the two drugs have fueled myriad explorations of their repurposing opportunities for the treatment of a wide variety of other human diseases involving immune dysregulation.

show abstract

Section: Monocytes and Macrophagesmentioning

confidence: 99%

Multifaceted Immunomodulatory Effects of the BTK Inhibitors Ibrutinib and Acalabrutinib on Different Immune Cell Subsets – Beyond B Lymphocytes

Zhu

Gokhale

Jung

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…Emerging clinical evidence shows that both acalabrutinib and ibrutinib have protective effects against pulmonary injury, decreasing the duration of mechanical ventilation and mortality rate for hospitalized patients with severe COVID-19 (138)(139)(140)(141). The protective effects of BTK inhibitors have also been observed in CLL patients with COVID-19, as the hospitalization rate and duration for severe COVID-19 is lower and shorter for CLL patients on ibrutinib versus those on other regimens or off treatment (142,(144)(145)(146).…”

Section: Covid-19 Sepsis and Other Infectious And Inflammatory Diseasesmentioning

confidence: 99%

Clinical Trials of the BTK Inhibitors Ibrutinib and Acalabrutinib in Human Diseases Beyond B Cell Malignancies

et al. 2021

View full text Add to dashboard Cite

The BTK inhibitors ibrutinib and acalabrutinib are FDA-approved drugs for the treatment of B cell malignances. Both drugs have demonstrated clinical efficacy and safety profiles superior to chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia. Mounting preclinical and clinical evidence indicates that both ibrutinib and acalabrutinib are versatile and have direct effects on many immune cell subsets as well as other cell types beyond B cells. The versatility and immunomodulatory effects of both drugs have been exploited to expand their therapeutic potential in a wide variety of human diseases. Over 470 clinical trials are currently registered at ClinicalTrials.gov to test the efficacy of ibrutinib or acalabrutinib not only in almost every type of B cell malignancies, but also in hematological malignancies of myeloid cells and T cells, solid tumors, chronic graft versus host disease (cGHVD), autoimmune diseases, allergy and COVID-19 (http:www.clinicaltrials.gov). In this review, we present brief discussions of the clinical trials and relevant key preclinical evidence of ibrutinib and acalabrutinib as monotherapies or as part of combination therapies for the treatment of human diseases beyond B cell malignancies. Adding to the proven efficacy of ibrutinib for cGVHD, preliminary results of clinical trials have shown promising efficacy of ibrutinib or acalabrutinib for certain T cell malignancies, allergies and severe COVID-19. However, both BTK inhibitors have no or limited efficacy for refractory or recurrent solid tumors. These clinical data together with additional pending results from ongoing trials will provide valuable information to guide the design and improvement of future trials, including optimization of combination regimens and dosing sequences as well as better patient stratification and more efficient delivery strategies. Such information will further advance the precise implementation of BTK inhibitors into the clinical toolbox for the treatment of different human diseases.

show abstract

“…Thus, there is a link between inflammation, immunity, angiotensin-converting enzyme 2, and cardiovascular damage. Systemic disease triggered by SARS-CoV-2 infection is primarily due to an exaggerated and inadequate immune response ( 13 ). The inflammatory response triggered by the virus is involved in increasing the production of proinflammatory cytokines, including TNFα, IL-1 and IL-6.…”

Section: Introductionmentioning

confidence: 99%

“…Hematopoietic cells contribute to increased VEGF production, which stimulates angiogenesis, and increases T-cell differentiation to Th17 cells and Tregs, as well as B-cell activation. This inflammatory process causes damage to various organs and tissues ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…Bruton tyrosine kinase inhibitors (BTKi) exhibit anti-inflammatory action due to their effects on both the innate immune system and platelets ( 14 ). Ibrutinib, through its immunomodulatory properties, may serve as a candidate for the treatment of clinical complications caused by excessive immune activation produced by the SARS-CoV-2 virus ( 13 ). Ibrutinib is able to reduce the production of TNFα, IL-1, IL-6, monocyte chemo-attractant protein-1, and VEGF, and it inhibits the hematopoietic cell kinase from neutrophils and macrophages involved in the regulation of cell survival and proliferation in response to IL-6 and related cytokines ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Management of patients with chronic lymphocytic leukemia during the SARS‑CoV‑2 pandemic (Review)

Mihăilă

2021

Oncol Lett

View full text Add to dashboard Cite

Oncohematological patients are prone to develop infections due to immunosuppression caused by the disease and chemo-immunotherapy. The aim of this review was to outline the details of the management of patients with chronic lymphocytic leukemia (CLL) during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Patients with CLL often exhibit inadequate humoral and cellular immune responses to various infections and vaccinations. Patients under the 'watch and wait' strategy have a lower risk of infections, including with SARS-CoV-2, compared with those undergoing therapeutic interventions, but they still have a higher risk than age-matched controls. Patients with CLL have a high risk of developing severe forms of coronavirus disease-2019 (COVID-19), particularly if they are undergoing chemo-immunotherapy. The total anti-SARS-CoV-2 antibody titer demonstrates a slower increase in patients with CLL infected with the virus, and the antibody levels tend to decrease after reaching a maximum level sooner than in healthy individuals. This leads to a late negativation of the PCR tests and a longer duration of hospitalization. In total, ~1/3 of patients with CLL do not develop a persistent titer of antiviral antibodies, and this is associated with the presence of hypogammaglobulinemia. It appears that patients with CLL have the worst outcomes amongst patients with malignant hemopathies and SARS-CoV-2 infection. Bruton tyrosine kinase inhibitors reduce the hyperinflammatory status of patients with CLL with COVID-19, which is accompanied by decreased levels of serum inflammatory markers, ferritin and D-dimer, and serum levels of pro-inflammatory cytokines, but they increase the risk of infections and impaired humoral immunity. An abrupt discontinuation of these may promote the rapid decompensation of CLL, which may even mimic the clinical manifestations of COVID-I9, including a significant increase in cytokine release. In conclusion, therapeutic decisions must be personalized to each patient with CLL and each at risk patient must be quarantined during the SARS-CoV-2 pandemic to reduce their risk of contraction. Contents

show abstract

May Ibrutinib Have Activity in Respiratory Complications by SARS-CoV-2? Clinical Experience in a Patient with Chronic Lymphocytic Leukemia

Cited by 5 publications

References 13 publications

Multifaceted Immunomodulatory Effects of the BTK Inhibitors Ibrutinib and Acalabrutinib on Different Immune Cell Subsets – Beyond B Lymphocytes

Multifaceted Immunomodulatory Effects of the BTK Inhibitors Ibrutinib and Acalabrutinib on Different Immune Cell Subsets – Beyond B Lymphocytes

Clinical Trials of the BTK Inhibitors Ibrutinib and Acalabrutinib in Human Diseases Beyond B Cell Malignancies

Management of patients with chronic lymphocytic leukemia during the SARS‑CoV‑2 pandemic (Review)

Contact Info

Product

Resources

About