Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome

Hines, Melissa; Knight, Tristan; McNerney, Kevin O.; Leick, Mark B.; Jain, Tania; Ahmed, Sairah; Frigault, Matthew J.; Hill, Joshua A.; Jain, Michael D.; Johnson, William T.; Lin, Yi; Mahadeo, Kris Michael; Maron, Gabriela; Marsh, Rebecca; Neelapu, Sattva S.; Nikiforow, Sarah; Ombrello, Amanda K.; Shah, Nirav N.; Talleur, Aimee C; Turicek, David P; Vatsayan, Anant; Wong, Sandy W.; Maus, Marcela V.; Komanduri, Krishna V.; Berliner, Nancy; Henter, Jan‐Inge; Perales, Miguel Angel; Frey, Noelle V.; Teachey, David T.; Frank, Matthew J.; Shah, Nirali N.

doi:10.1016/j.jtct.2023.03.006

Cited by 106 publications

(88 citation statements)

References 148 publications

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“…Grade 2 IEC-HS represents mild-moderate symptoms requiring intervention with immunosuppression and fibrinogen concentrate/cryoprecipitate for asymptomatic hypofibrinogenaemia. Grade 3 IEC-HS events are severe/clinically significant, for example hospitalisation for coagulopathy-bleeding/kidney injury/hypotension/respiratory distress, whilst grade 4 events are life-threatening, requiring urgent intervention 36 . Treatments include the interleukin-1 receptor antagonist anakinra and corticosteroids.…”

Section: Supportive Care For Car-t Therapy Admission (From Ld To Day 28)mentioning

confidence: 99%

“…IEC-HS (grades 1-5) is a rare, life-threatening hyperinflammatory syndrome with features of macrophage activation/haemophagocytic lymphohistiocytosis that can occur as CRS is resolved/resolving [36]. Hallmarks include fever, cytopenias, hyperferritinaemia [ > 2× upper limit of normal (ULN) or baseline (at infusion)], new onset splenomegaly, transaminitis [ > 5× ULN if baseline normal or > 5× baseline (if baseline abnormal)] and coagulopathy with hypofibrinogenaemia (< 150 mg/dl or < lower limit of normal) [36]. Grade 1 IEC-HS presents as asymptomatic/mild symptoms and requires close observation/twice daily blood tests.…”

Section: Immune Effector Cell-associated Haemophagocytic Lymphohistio...mentioning

confidence: 99%

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Supportive care for chimeric antigen receptor T-cell patients

Springell

O’Reilly

Roddie

2023

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of review The purpose of this review is to provide clear guidance to health professionals delivering chimeric antigen receptor T-cell (CAR-T) therapy on the best supportive management throughout the CAR-T pathway, from referral to long-term follow-up, including psychosocial aspects. Recent findings CAR-T therapy has changed the treatment landscape for relapsed/refractory (r/r) B-cell malignancy. Approximately 40% of r/r B-cell leukaemia/lymphoma patients receiving CD19-targeted CAR-T therapy achieve durable remission following a single dose. The field is rapidly expanding to encompass new CAR-T products for indications such as multiple myeloma, mantle cell lymphoma and follicular lymphoma, and the number of patients eligible to receive CAR-T therapy is likely to continue to grow exponentially. CAR-T therapy is logistically challenging to deliver, with involvement of many stakeholders. In many cases, CAR-T therapy requires an extended inpatient hospital admission, particularly in older, comorbid patients, and is associated with potentially severe immune side effects. Further, CAR-T therapy can lead to protracted cytopenias that can last for several months accompanied by a susceptibility to infection. Summary For the reasons listed above, standardised, comprehensive supportive care is critically important to ensure that CAR-T therapy is delivered as safely as possible and that patients are fully informed of the risks and benefits, as well as the requirement for extended hospital admission and follow-up, to fully realise the potential of this transformative treatment modality.

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Section: Supportive Care For Car-t Therapy Admission (From Ld To Day 28)mentioning

confidence: 99%

Section: Immune Effector Cell-associated Haemophagocytic Lymphohistio...mentioning

confidence: 99%

Supportive care for chimeric antigen receptor T-cell patients

Springell

O’Reilly

Roddie

2023

Current Opinion in Supportive &Amp; Palliative Care

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“…26 Furthermore, cytopenias can be delayed in nature, and the expected "on target off-tumor" effects result in long-term B-cell aplasia and antibody deficiencies (Figure 1). 25,[27][28][29][30][31][32] The risk for infection after CAR-T-cell therapy is high due to these and other factors, 33 creating unique challenges and opportunities for infection prevention.…”

Section: Introductionmentioning

confidence: 99%

Infections after chimeric antigen receptor (CAR)‐T‐cell therapy for hematologic malignancies

Kampouri,

Little,

Rejeski

et al. 2023

Transplant Infectious Dis

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BackgroundChimeric antigen receptor (CAR)‐T‐cell therapies have revolutionized the management of acute lymphoblastic leukemia, non‐Hodgkin lymphoma, and multiple myeloma but come at the price of unique toxicities, including cytokine release syndrome, immune effector cell‐associated neurotoxicity syndrome, and long‐term “on‐target off‐tumor” effects.MethodsAll of these factors increase infection risk in an already highly immunocompromised patient population. Indeed, infectious complications represent the key determinant of non‐relapse mortality after CAR‐T cells. The temporal distribution of these risk factors shapes different infection patterns early versus late post‐CAR‐T‐cell infusion. Furthermore, due to the expression of their targets on B lineage cells at different stages of differentiation, CD19, and B‐cell maturation antigen (BCMA) CAR‐T cells induce distinct immune deficits that could require different prevention strategies. Infection incidence is the highest during the first month post‐infusion and subsequently decreases thereafter. However, infections remain relatively common even a year after infusion.ResultsBacterial infections predominate early after CD19, while a more equal distribution between bacterial and viral causes is seen after BCMA CAR‐T‐cell therapy, and fungal infections are universally rare. Cytomegalovirus (CMV) and other herpesviruses are increasingly breported, but whether routine monitoring is warranted for all, or a subgroup of patients, remains to be determined. Clinical practices vary substantially between centers, and many areas of uncertainty remain, including CMV monitoring, antibacterial and antifungal prophylaxis and duration, use of immunoglobulin replacement therapy, and timing of vaccination.ConclusionRisk stratification tools are available and may help distinguish between infectious and non‐infectious causes of fever post‐infusion and predict severe infections. These tools need prospective validation, and their integration in clinical practice needs to be systematically studied. image

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“…Promising breakthroughs in the treatment of solid organ malignancies and autoimmune diseases raise hope that CAR‐T cell therapy may play an even broader role in the future 15,16 . CAR‐T cell therapy is associated with well‐known early toxicities including cytokine release syndrome (CRS), immune effector cell‐associated neurotoxicity syndrome (ICANS), and immune effector‐cell associated hemophagocytic lymphohistiocytosis‐like syndrome (IEC‐HS), the assessment and management of which have been thoroughly described in consensus guidelines by the American Society for Transplantation and Cellular Therapy (ASTCT), European Society for Blood and Marrow Transplantation (EBMT), National Comprehensive Cancer Network (NCCN), and American Society of Clinical Oncology (ASCO) 17–21 . However, comparatively less is known about the late effects of CAR‐T cell therapy, an issue of growing importance given the rapidly increasing number of long‐term survivors.…”

Section: Introductionmentioning

confidence: 99%

“…15,16 CAR-T cell therapy is associated with well-known early toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and immune effectorcell associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), the assessment and management of which have been thoroughly described in consensus guidelines by the American Society for Transplantation and Cellular Therapy (ASTCT), European Society for Blood and Marrow Transplantation (EBMT), National Comprehensive Cancer Network (NCCN), and American Society of Clinical Oncology (ASCO). [17][18][19][20][21] However, comparatively less is known about the late effects of CAR-T cell therapy, an issue of growing importance given the rapidly increasing number of long-term survivors. Indeed, CAR-T cells may persist in vivo for >10 years after infusion 22,23 and have been implicated in a variety of persistent and/or delayed onset complications that pose unique clinical challenges.…”

mentioning

confidence: 99%

Long‐term survivorship care after CAR‐T cell therapy

Puckrin,

Jamani,

Jimenez‐Zepeda

2023

European J of Haematology

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While cytokine release syndrome and immune effector cell‐associated neurotoxicity syndrome are well‐recognized acute toxicities of chimeric antigen receptor (CAR) T cell therapy, these complications have become increasingly manageable by protocolized treatment algorithms incorporating the early administration of tocilizumab and corticosteroids. As CAR‐T cell therapy expands to new disease indications and the number of long‐term survivors steadily increases, there is growing recognition of the need to appropriately evaluate and manage the late effects of CAR‐T cell therapy, including late‐onset or persistent neurotoxicity, prolonged cytopenias, delayed immune reconstitution and infections, subsequent malignancies, organ dysfunction, psychological distress, and fertility implications. In this review, we provide a practical approach to the long‐term survivorship care of the CAR‐T cell recipient, with a focus on the optimal strategies to address the common and challenging late complications affecting this unique population.

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Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome

Cited by 106 publications

References 148 publications

Supportive care for chimeric antigen receptor T-cell patients

Supportive care for chimeric antigen receptor T-cell patients

Infections after chimeric antigen receptor (CAR)‐T‐cell therapy for hematologic malignancies

Long‐term survivorship care after CAR‐T cell therapy

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