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Adverse Event Management

Adverse Event Management

Infusion-related reactions

Incidence1


Table adapted from BESPONSA Hong Kong Prescribing Information November 2018

Characterisation with BESPONSA1

  • All events were Grade ≤2 in severity
  • They generally occurred in Cycle 1 and shortly after the end of the BESPONSA infusion
  • They resolved spontaneously or with medical management

Management1

Before treatment

  • BESPONSA is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients (sucrose, polysorbate 80, sodium chloride, tromethamine)
  • Premedication with a corticosteroid, antipyretic and antihistamine is recommended prior to dosing

During treatment

  • Patients should be monitored closely during and for at least 1 hour after the end of the infusion for the potential onset of infusion-related reactions, including symptoms such as hypotension, hot flush or breathing problems
  • If an infusion-related reaction occurs, the infusion should be interrupted and appropriate medical management should be instituted
  • Depending on the severity of the infusion-related reaction, discontinuation of the infusion or administration of steroids and antihistamines should be considered
  • For severe or life-threatening infusion-related reactions, treatment should be permanently discontinued

Click here to refer to the abbreviated PI, and learn more about the management of infusion-related reactions.

Tumour lysis syndrome

Incidence1


Table adapted from BESPONSA Hong Kong Prescribing Information November 2018

Characterisation with BESPONSA1

Tumour lysis syndrome (TLS), which may be life-threatening or fatal, was reported in 4/164 (2%) of pateints:

  • Grade 3/4 TLS was reported in 3/164 (2%) of patients
  • TLS occurred shortly after the end of the BESPONSA infusion and resolved with medical management

Management

  • Premedication to reduce uric acid levels and hydration is recommended before BESPONSA dosing for patients with a high tumour burden1
  • Patients should be monitored for signs and symptoms of TLS and treated according to standard medical practice1

Click here to refer to the abbreviated PI, and learn more about the management of TLS.

Increased amylase and lipase

Incidence1


Table adapted from BESPONSA Hong Kong Prescribing Information November 2018

Management1

  • Patients should be monitored for increases in amylase and lipase. Potential hepatobiliary disease should be evaluated and treated according to standard medical practice

Click here to refer to the abbreviated PI, and learn more about the management of increased amylase and lipase.

Myelosuppression/cytopenias

Incidence1


Table adapted from BESPONSA Hong Kong Prescribing Information November 2018

Characterisation with BESPONSA1

  • In patients receiving BESPONSA, neutropenia, thrombocytopenia, anaemia, leucopenia, febrile neutropenia, lymphopenia and pancytopenia, some of which were life-threatening, have been reported
  • Complications associated with neutropenia and thrombocytopenia (including infections and bleeding/haemorrhagic events, respectively) were reported in some patients

Management

  • Complete blood counts should be monitored prior to each dose of BESPONSA and signs and symptoms of infection, bleeding/haemorrhage and other effects of myelosuppression should be monitored during treatment1
  • As appropriate, prophylactic anti-infectives should be administered and surveillance testing should be employed during and after treatment
    – Consider using granulocyte-colony stimulating factor as a management technique for myelosuppression/ cytopenias4
  • Management of severe infection, bleeding/haemorrhage and other effects of myelosuppression, including severe neutropenia or thrombocytopenia, may require dosing interruption, dose reduction or discontinuation of BESPONSA1
  • Platelet transfusion remains a common intervention in the management of thrombocytopenia in patients with leukaemia3

Click here to refer to the abbreviated PI, and learn more about the management of myelosuppression/cytopenias.

Bleeding events

Incidence1


*The most common bleeding event was epistaxis, which was reported in 15% of patients.

Table adapted from BESPONSA Hong Kong Prescribing Information November 2018

Management1

  • Complete blood counts should be monitored before each dose of BESPONSA, and signs and symptoms of bleeding/haemorrhage should be monitored during treatment
  • Management of bleeding/haemorrhage may require a dosing interruption, dose reduction or discontinuation of BESPONSA

Click here to refer to the abbreviated PI, and learn more about the management of bleeding events.

Infection

Incidence1


*Fatal infections included pneumonia, neutropenic sepsis, sepsis, septic shock and Pseudomonas sepsis.

Table adapted from BESPONSA Hong Kong Prescribing Information November 2018

Management1

  • Complete blood counts should be monitored before each dose of BESPONSA, and signs and symptoms of infection should be monitored during treatment. As appropriate, prophylactic anti-infectives should be administered and surveillance testing should be employed during and after treatment
  • Management of severe infection may require a dosing interruption, dose reduction or discontinuation of treatment

Click here to refer to the abbreviated PI, and learn more about the management of infection.

Hepatotoxicity

Incidence1


Table adapted from BESPONSA Hong Kong Prescribing Information November 2018

Click here to refer to the abbreviated PI, and learn more about the management of Hepatotoxicity.

Characterisation with BESPONSA1

  • Hepatotoxicity, including severe, life-threatening and sometimes fatal hepatic VOD/SOS, was reported in patients with relapsed or refractory ALL receiving BESPONSA

Monitoring

  • In all patients, liver tests should be monitored, including, ALT, AST, total bilirubin, and ALP, prior to and following each dose of BESPONSA
  • For patients who develop abnormal liver tests, liver tests and clinical signs and symptoms of hepatotoxicity should be monitored more frequently
  • For patients who proceed to HSCT, liver tests should be monitored closely during the first month post‑HSCT, then less frequently thereafter, according to standard medical practice

Dose modifications

  • No adjustment to the starting dose is required in patients with hepatic impairment defined by total bilirubin ≤1.5 × ULN and AST/ALT ≤2.5 × ULN
  • Interrupt dosing until recovery of total bilirubin to ≤1.5 × ULN and AST/ALT to ≤2.5 × ULN prior to each dose unless due to Gilbert’s syndrome or haemolysis
  • Permanently discontinue treatment if total bilirubin does not recover to ≤1.5 × ULN or AST/ALT does not recover to ≤2.5 × ULN

VOD/SOS

Characterisation with BESPONSA1

BESPONSA significantly increased the risk of VOD/SOS above that of standard chemotherapy regimens in this patient population. This risk was most marked in patients who underwent subsequent haematopoietic stem cell transplantation (HSCT).

  • VOD/SOS was reported in 23/164 (14%) patients receiving BESPONSA during or after treatment, or after an HSCT after completion of treatment
  • VOD/SOS was reported in 5/164 (3%) patients during BESPONSA treatment or during follow-up without an intervening HSCT (two of these five patients had also received an HSCT before BESPONSA treatment)
  • VOD/SOS was reported in 18/79 (23%) patients treated with BESPONSA who proceeded to HSCT

Signs and symptoms of VOD/SOS2

  • Elevations in total bilirubin
  • Rapid weight gain
  • Fluid retention
  • Ascites
  • Hepatomegaly
  • Jaundice

Risk factors relating to BESPONSA1

The reported frequency of VOD/SOS post HSCT was highest in the following subgroups:

  • Patients who received an HSCT-conditioning regimen containing two alkylating agents
  • Patients aged ≥65 years
  • Patients with a serum bilirubin ≥ upper limit of normal before HSCT

Other patient factors that appear to be associated with an increased risk of VOD/SOS after HSCT include a prior HSCT, age ≥55 years, a history of liver disease or hepatitis before treatment, later salvage lines and a greater number of treatment cycles.

VOD/SOS: Diagnosis and risk factors

Professor Matthias Stelljes talks about diagnosis of VOD/SOS and the main risk factors.

Prevention and management of VOD/SOS1

  • BESPONSA is contraindicated in:
    • Patients who have experienced prior confirmed severe or ongoing VOD/SOS
    • Patients with serious ongoing hepatic disease (e.g. cirrhosis, nodular regenerative hyperplasia, active hepatitis)
  • The use of HSCT-conditioning regimens containing two alkylating agents should be avoided. The benefit–risk should be carefully considered before administering BESPONSA to patients in whom the future use of HSCT-conditioning regimens containing two alkylating agents is likely unavoidable
  • For patients proceeding to HSCT the recommended duration of treatment is two cycles, with a maximum of three cycles, to reduce the risk of VOD/SOS
  • Signs and symptoms of VOD/SOS should be monitored closely in all patients, especially post HSCT
  • Treatment should be permanently discontinued if VOD/SOS occurs. If severe VOD/SOS occurs, the patient should be treated according to standard medical practice

VOD/SOS: clinical characterisation, prevention and management

Professor David Marks discusses clinical characterisation, prevention and management of VOD/SOS.

Click here to refer to the abbreviated PI, and learn more about diagnosis, prevention and management of VOD/SOS.

  1. BESPONSA®​ Prescribing Information. Pfizer Corporation Hong Kong Limited. Version Nov 2018.
  2. Mohty M et al. Bone Marrow Transplant 2016;51:906-912.
  3. Tfayli A, et al. Management of Thrombocytopenia in Patients With Leukemia. Medscape (Accessed February 20, 2020, at https://www.medscape.org/viewarticle/569207).
  4. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the Use of WBC Growth Factors: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2015;33(28):3199-3212. doi:10.1200/JCO.2015.62.3488.