EHA 2019 – How to manage the toxicity of new agents used in oncohematology

  • Elena Riboldi — Agenzia Zoe
  • Univadis
L'accesso ai contenuti di questo sito è riservato agli operatori del settore sanitario italiano L'accesso ai contenuti di questo sito è riservato agli operatori del settore sanitario italiano


  • Adverse events (AEs) related to immune- and targeted therapy are different from the classical chemotherapy-related toxicities and their recognition may be challenging.
  • Oncologists should inform patients and treating physician on the possible toxicities and discuss with specialists how to manage comorbidities and comedications.


Why this matters

  • The use of immunotherapy and targeted therapy is on the rise.


Key points from the symposium


Immune checkpoint inhibitors (ICIs)

  • Immune-related adverse events (irAEs) can virtually affect every tissue or organ.
  • Different agents have different toxicity profiles (anti-PD-1: pneumonitis, myalgia, arthralgia, hypothyroidism; anti-CTLA: colitis, hypophysitis).
  • Patients, relatives, and caregivers should be briefed on potential irAEs symptoms.
  • Any new unclear symptom should be timely worked-up.
  • Full work-up is also needed in asymptomatic laboratory changes.
  • Rapid treatment to inhibit acute phase of inflammation and its sustainment is recommended (0.5-2 mg/kg body weight prednisolone).
  • Immunosuppressive strategy should be based on the tissue affected and predominant immune infiltrate.
  • Grade 1 AE: continue ICI (close monitoring); grade 2-3: hold; grade 4: discontinue.


Bruton's tyrosine kinase (BTK) inhibitors

  • AEs include cardiotoxicity, bleeding, infections, arthralgia, skin rash.
  • Infection prophylaxis: same guidelines as with chemotherapy but monitor for opportunistic infections.
  • Ventricular and atrial arrhythmias (atrial fibrillation [AF]: up to 16%) and hypertension incidence is increased in patients on ibrutinib.
  • The first step for AF management is risk assessment.
  • In case of ibrutinib-associated AF, cardiologist advice is mandatory.
  • If AF is adequately controlled, hold ibrutinib.
  • Outside anticoagulant and antiplatelet therapy bleeding risk is low.
  • When antiplatelet therapy is needed, bleeding risk is higher with one drug (consider ibrutinib+low-dose aspirin) but unacceptable with two drugs (discontinue ibrutinib).
  • When anticoagulants are needed bleeding risk is higher and increased by drug interactions.
  • Ibrutinib treatment decision should include assessment of cardiovascular risk and extensive analysis of comedications (CYP3A4/5 inducers/inhibitors).


Expert commentary

  • “Oncologists are quite well aware of the problem, what is more important is that the physician and the patient are aware of it. We should not forget that we do not see these patients all the time, they are not in hospital, these are oral drugs. We really have to raise awareness among their treating physicians.”
  • “For ibrutinib the most important is cardiovascular toxicity. Personally, I always prescribe Holter and echography before starting treatment. It does not mean that I am not going to give ibrutinib, it means that I am aware of the possible toxicities and I have discussed with the cardiologists on how to use the drug, if I should I treat the patient preventively or not. This is the safe way to do it.” Florence Cymbalista, MD at Hôpital Avicenne and Professor at Université Paris 13 (France).