Table 3. Key unanswered questions and... | American Society of Hematology

Table 3.

Key unanswered questions and future directions

Key unanswered questions	Future directions
Diagnosis and surveillance
What is the optimal method of monitoring patients for the development of cardiotoxicity? Can biomarkers be used for the early detection of cardiotoxicity? What are the most effective biomarker cutoff values for the detection/monitoring of cardiotoxicity?	More support for large-scale postmarketing pharmacovigilance studies investigating the link between biomarker changes and the development of cardiovascular toxicity. Large-scale RCTs comparing different surveillance strategies.
Management and prevention
CRS Does prophylactic therapy against CRS improve overall survival? Which drugs/drug combinations (tocilizumab, siltuximab, corticosteroids, and anakinra) are the most effective for the treatment/prevention of CRS? When is the best timing to initiate prophylactic therapy against CRS? Non-CRS What is the role of contemporary cardioprotective therapies (eg, beta blockers, ACE inhibitor, and statins, etc) in the management and prevention of cardiotoxicity? What is the ideal balance between maintaining adequate cancer therapy levels and cardiotoxicity, that is, permissive cardiotoxicity?	RCTs assessing the comparative efficacy of CRS prophylactic regimens. Develop unified pretreatment risk assessment tools based on known risk factors and the integration of cardio-oncology services in high-risk patients. RCTs assessing the comparative efficacy of cardioprotective therapies at preventing new-onset cardiac dysfunction. RCTs comparing different levels of permissive cardiotoxicity with respect to eventual outcomes.
Risk factors
What are the key risk factors for developing cardiotoxicity from cellular therapies? What are the unique cardiotoxicity risks of individual cellular therapies?	Conduct studies to identify and validate risk factors for cardiotoxicity.
Long-term prognostic implications
What are the long-term cardiovascular consequences of cellular therapies and how does this affect overall survival and patient quality of life?	Conduct long-term follow-up studies to assess the late-onset cardiovascular effects of cellular therapies.

Key unanswered questions	Future directions
Diagnosis and surveillance
What is the optimal method of monitoring patients for the development of cardiotoxicity? Can biomarkers be used for the early detection of cardiotoxicity? What are the most effective biomarker cutoff values for the detection/monitoring of cardiotoxicity?	More support for large-scale postmarketing pharmacovigilance studies investigating the link between biomarker changes and the development of cardiovascular toxicity. Large-scale RCTs comparing different surveillance strategies.
Management and prevention
CRS Does prophylactic therapy against CRS improve overall survival? Which drugs/drug combinations (tocilizumab, siltuximab, corticosteroids, and anakinra) are the most effective for the treatment/prevention of CRS? When is the best timing to initiate prophylactic therapy against CRS? Non-CRS What is the role of contemporary cardioprotective therapies (eg, beta blockers, ACE inhibitor, and statins, etc) in the management and prevention of cardiotoxicity? What is the ideal balance between maintaining adequate cancer therapy levels and cardiotoxicity, that is, permissive cardiotoxicity?	RCTs assessing the comparative efficacy of CRS prophylactic regimens. Develop unified pretreatment risk assessment tools based on known risk factors and the integration of cardio-oncology services in high-risk patients. RCTs assessing the comparative efficacy of cardioprotective therapies at preventing new-onset cardiac dysfunction. RCTs comparing different levels of permissive cardiotoxicity with respect to eventual outcomes.
Risk factors
What are the key risk factors for developing cardiotoxicity from cellular therapies? What are the unique cardiotoxicity risks of individual cellular therapies?	Conduct studies to identify and validate risk factors for cardiotoxicity.
Long-term prognostic implications
What are the long-term cardiovascular consequences of cellular therapies and how does this affect overall survival and patient quality of life?	Conduct long-term follow-up studies to assess the late-onset cardiovascular effects of cellular therapies.

RCT, randomized controlled trial.