Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer

Ragoonanan, Dristhi; Khazal, Sajad; Abdel‐Azim, Hisham; McCall, David; Cuglievan, Branko; Tambaro, Francesco Paolo; Ahmad, Ali; Rowan, Courtney M.; Gutiérrez, Cristina; Schadler, Keri; Li, Shulin; Nardo, Matteo Di; Chi, Linda; Gulbis, Alison; Shoberu, Basirat; Mireles, Maria E.; McArthur, Jennifer; Kapoor, Neena; Miller, Jeffrey D.; Fitzgerald, Julie C.; Tewari, Priti; Petropoulos, Demetrios; Gill, Jonathan; Duncan, Christine; Lehmann, Leslie; Hingorani, Sangeeta; Angelo, Joseph; Swinford, Rita D.; Steiner, Marie; Tejada, Fiorela N. Hernandez; Martin, Paul L.; Auletta, Jeffery J.; Choi, Sung Won; Bajwa, Rajinder; Garnes, Natalie Dailey; Kebriaei, Partow; Rezvani, Katayoun; Wierda, William G.; Neelapu, Sattva S.; Shpall, Elizabeth J.; Corbacioglu, Selim; Mahadeo, Kris Michael

doi:10.1038/s41571-021-00474-4

Cited by 43 publications

(46 citation statements)

References 186 publications

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“…Importantly, a broad consensus statement offering updated comprehensive recommendations for the treatment of toxicities associated with immunotherapies has been recently published. 65 Though many aspects remain unknown, mechanisms underlying CRS and ICANS have become clearer. Several factors contribute to different toxicity rates.…”

Section: Chimeric Antigen Receptor T-cell Toxicity In Multiple Myelomamentioning

confidence: 99%

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European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma

Bruno¹,

Wäsch

Engelhardt

et al. 2021

haematol

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Chimeric antigen receptor (CAR) T cells (CAR-T) have dramatically changed the treatment landscape of B-cell malignancies, providing a potential cure for relapsed/refractory patients. Long-term responses in patients with acute lymphoblastic leukemia and non Hodgkin lymphomas have encouraged further development in myeloma. In particular, B-cell maturation antigen (BCMA)-targeted CAR-T have established very promising results in heavily pre-treated patients. Moreover, CAR-T targeting other antigens (i.e., SLAMF7 and CD44v6) are currently under investigation. However, none of these current autologous therapies have been approved, and despite high overall response rates across studies, main issues such as long-term outcome, toxicities, treatment resistance, and management of complications limit as yet their widespread use. Here, we critically review the most important pre-clinical and clinical findings, recent advances in CAR-T against myeloma, as well as discoveries in the biology of a still incurable disease, that, all together, will further improve safety and efficacy in relapsed/refractory patients, urgently in need of novel treatment options.

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Section: Chimeric Antigen Receptor T-cell Toxicity In Multiple Myelomamentioning

confidence: 99%

“…Several factors contribute to different toxicity rates. 65 Moreover, incidence and severity of adverse effects vary between diseases. While the incidence of any grade CRS is comparable between diseases, CRS severity (≥grade 3) is highest in patients with ALL and lowest in MM.…”

Section: Chimeric Antigen Receptor T-cell Toxicity In Multiple Myelomamentioning

confidence: 99%

European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma

Bruno¹,

Wäsch

Engelhardt

et al. 2021

haematol

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“…Despite the aforementioned benefits, targeted therapies and immunologic strategies are also fraught with side effects and even life-threatening toxicities which require special caution, early detection, and initiation of age-appropriate countermeasures in children and adolescents [ 73 ]. For molecular targeted therapies, the majority of adverse effects are of low to moderate severity and predictable on-target toxicities of the inhibited signaling pathway but life-threatening complications may also occur [ 74 ].…”

Section: Cancer Therapies and Risks Of Second Primary Malignanciesmentioning

confidence: 99%

Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies

Zahnreich

Schmidberger

2021

Cancers

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Cancer represents the leading cause of disease-related death and treatment-associated morbidity in children with an increasing trend in recent decades worldwide. Nevertheless, the 5-year survival of childhood cancer patients has been raised impressively to more than 80% during the past decades, primarily attributed to improved diagnostic technologies and multiagent cytotoxic regimens. This strong benefit of more efficient tumor control and prolonged survival is compromised by an increased risk of adverse and fatal late sequelae. Long-term survivors of pediatric tumors are at the utmost risk for non-carcinogenic late effects such as cardiomyopathies, neurotoxicity, or pneumopathies, as well as the development of secondary primary malignancies as the most detrimental consequence of genotoxic chemo- and radiotherapy. Promising approaches to reducing the risk of adverse late effects in childhood cancer survivors include high precision irradiation techniques like proton radiotherapy or non-genotoxic targeted therapies and immune-based treatments. However, to date, these therapies are rarely used to treat pediatric cancer patients and survival rates, as well as incidences of late effects, have changed little over the past two decades in this population. Here we provide an overview of the epidemiology and etiology of childhood cancers, current developments for their treatment, and therapy-related adverse late health consequences with a special focus on second primary malignancies.

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“…Targeting those antigens with CAR T-cells may result in profound myelosuppression due to lack of specificity and, hence, may mainly be a bridge to transplant [4][5][6]. In addition, immunotherapies have been associated with severe off-target systemic toxicities, including cytokine-release syndrome, immune cell-associated neurotoxicity syndrome, and graft-versus-host-disease [32].…”

Section: Oncolytic Virusesmentioning

confidence: 99%

Paving the Way for Immunotherapy in Pediatric Acute Myeloid Leukemia: Current Knowledge and the Way Forward

Koedijk

Werf

Calkoen

et al. 2021

Cancers

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Immunotherapeutic agents may be an attractive option to further improve outcomes and to reduce treatment-related toxicity for pediatric AML. While improvements in outcome have been observed with immunotherapy in many cancer types, immunotherapy development and implementation into patient care for both adult and pediatric AML has been hampered by an incomplete understanding of the bone marrow environment and a paucity of tumor-specific antigens. Since only a minority of patients respond in most immunotherapy trials across different cancer types, it will be crucial to understand which children with AML are likely to respond to or may benefit from immunotherapies. Immune cell profiling efforts hold promise to answer this question, as illustrated by the development of predictive scores in solid cancers. Such information on the number and phenotype of immune cells during current treatment regimens will be pivotal to generate hypotheses on how and when to intervene with immunotherapy in pediatric AML. In this review, we discuss the current understanding of the number and phenotype of immune cells in the bone marrow in pediatric AML, ongoing immunotherapy trials and how comprehensive immune profiling efforts may pave the way for successful clinical trials (and, ultimately, implementation into patient care).

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Diagnosis, grading and management of toxicities from immunotherapies in children, adolescents and young adults with cancer

Cited by 43 publications

References 186 publications

European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma

European Myeloma Network perspective on CAR T-Cell therapies for multiple myeloma

Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies

Paving the Way for Immunotherapy in Pediatric Acute Myeloid Leukemia: Current Knowledge and the Way Forward

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