Continuous renal replacement therapy in cytokine release syndrome following immunotherapy or cellular therapies?

Abstract

Recently, an increasing number of novel drugs were approved in oncology and hematology. Nevertheless, pharmacology progress comes with a variety of side effects, of which cytokine release syndrome (CRS) is a potential complication of some immunotherapies that can lead to multiorgan failure if not diagnosed and treated accordingly. CRS generally occurs with therapies that lead to highly activated T cells, like chimeric antigen receptor T cells or in the case of bispecific T-cell engaging antibodies. This, in turn, leads to a proinflammatory state with subsequent organ damage. To better manage CRS there is a need for specific therapies or to repurpose strategies that are already known to be useful in similar situations. Current management strategies for CRS are represented by anticytokine directed therapies and corticosteroids. Based on its pathophysiology and the resemblance of CRS to sepsis and septic shock, as well as based on the principles of initiation of continuous renal replacement therapy (CRRT) in sepsis, we propose the rationale of using CRRT therapy as an adjunct treatment in CRS where all the other approaches have failed in controlling the clinically significant manifestations.

Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward

“…This study has demonstrated that CRRT is effective in mitigating sepsis which has a similar pathophysiological mechanism to CRS (111). However, as such studies themselves indicate that there are still various unanswered questions in this field that require addressing (111).…”

“…It is important to state that in this case, tocilizumab and glucocorticoids were not successful in controlling the mentioned adverse events (110). Furthermore, another study has also proposed that continuous renal replacement therapy (CRRT) can be an additional approach for controlling CAR-T therapy-related CRS that is resistant to conventional treatment (111). This study has demonstrated that CRRT is effective in mitigating sepsis which has a similar pathophysiological mechanism to CRS (111).…”

“…Furthermore, another study has also proposed that continuous renal replacement therapy (CRRT) can be an additional approach for controlling CAR-T therapy-related CRS that is resistant to conventional treatment (111). This study has demonstrated that CRRT is effective in mitigating sepsis which has a similar pathophysiological mechanism to CRS (111). However, as such studies themselves indicate that there are still various unanswered questions in this field that require addressing (111).…”

Continuous Renal Replacement Therapy with oXiris Filter May Not Be an Effective Resolution to Alleviate Cytokine Release Syndrome in non-AKI Patients with Severe and Critical COVID-19

“…Using CRRT for immunomodulation has a long history in clinic for tapering cytokine storms and controlling the associated dysregulation of the immune system. This approach has also been proposed as adjuvant therapy in many diseases, including sepsis (22), septic AKI (35), septic shock (32), severe Middle East Respiratory Syndrome (MERS) (5), severe acute pancreatitis (SAP) with or without ARDS (9,11), CRS induced by some immunotherapies (7), severe burns (27), etc. Yet, a non-selective way allows harmful and bene cial substances to be simultaneously removed during CRRT (33).…”

Overview of the Side-Effects of FDA- and/or EMA-Approved Targeted Therapies for the Treatment of Hematological Malignancies

“…These are T-cells that are engineered to present a receptor for a specific antigen that, when encountering the antigen, activate the engineered T-cell. A common effect among this class of therapeutics is cytokine release syndrome (CRS) that occurs between 60% and 80% of treated patients [ 38 , 39 , 40 , 41 ]. CRS is characterized by a massive release of inflammatory cytokines and subsequent multiorgan dysfunction.…”