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ESMO management and treatment adapted recommendations in the COVID-19 era: Multiple myeloma

The tiered approach of ESMO in delivering a guidance for cancer patients during the COVID-19 pandemic is designed across three levels of priorities, namely: tier 1 (high priority intervention), 2 (medium priority) and 3 (low priority) – defined according to the criteria of the Cancer Care Ontario, Huntsman Cancer Institute and ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS), incorporating the information on the value-based prioritisation and clinical cogency of the interventions

  • High priority: Patient's condition is immediately life threatening, clinically unstable, and/or the magnitude of benefit qualifies the intervention as high priority (e.g. significant overall survival [OS] gain and/or substantial improvement in quality of life [QoL]);
  • Medium priority: Patient's situation is non-critical but delay beyond 6 weeks could potentially impact overall outcome and/or the magnitude of benefit qualifies for intermediate priority;
  • Low priority: Patient's condition is stable enough that services can be delayed for the duration of the COVID-19 pandemic and/or the intervention is non-priority based on the magnitude of benefit (e.g. no survival gain with no change nor reduced QoL).

Priorities for Multiple Myeloma patients

Priorities for Multiple Myeloma: Medical Oncology*

Young, transplant-eligible patients

High Priority

  • Patients with newly diagnosed active/high-risk disease (SLiM-CRAB criteria present):
    • Treatment should not be postponed
    • Therapeutic decisions should be made on a case-by-case basis, considering disease stage, risk, age, cytogenetics/FISH, comorbidities
    • Consider G-CSF support to minimise risk of neutropaenia

Medium Priority

  • Patients on continuous first-line treatment:
    • Consider delaying ASCT and prolong induction regimen for up to 6-8 cycles
    • Patients scheduled to undergo ASCT should be tested for COVID-19 before ASCT
    • For standard-risk patients, consider delaying ASCT by additional induction cycles and/or lenalidomide maintenance (no proven OS benefit for early treatment in this setting compared with modern 3-drug induction followed by lenalidomide maintenance therapy without ASCT consolidation)
    • Use interval phone and/or virtual visits whenever possible to monitor tolerability of treatment, to decrease clinic visits
    • Consider extending access to lenalidomide for up to 2 months for patients receiving maintenance therapy (with telemedicine/remote lab tests in between)
    • In patients in need of IVIg replacement, consider administration at reduced frequency
    • Consider G-CSF support to minimise neutropaenia

 Low Priority

  • Patients in stable remission (currently without active treatment):
    • Delay follow-up visits and/or perform by telemedicine if possible
    • Delay antiresorptive therapy (zoledronic acid, denosumab) and/ or reduce frequency (e.g. every 3 months)
 
Elderly, transplant non-eligible patients with newly diagnosed MM

High Priority

  • Patients with newly diagnosed active/high-risk disease (SLiM-CRAB criteria present):
    • Treatment should not be postponed
    • Therapeutic decisions should be made on a case-by-case basis, considering disease stage, risk, age, cytogenetics/FISH, comorbidities
    • Consider G-CSF support to minimise risk of neutropaenia

Medium Priority

  • Patients on continuous treatment:
    • Patients responding to lenalidomide/dexamethasone: consider discontinuation of dexamethasone and maintain response with lenalidomide alone
    • Prefer prescription of orally available drugs
    • If parenteral drug administration is necessary, consider using it at reduced frequency
    • Use interval phone and/or virtual visits whenever possible to monitor tolerability and outcome
    • Reduce dexamethasone dose to ≤20 mg weekly
    • Consider G-CSF support to minimise risk of neutropaenia

 Low Priority

  • Patients in stable remission on continuous treatment (or without active treatment):
    • Delay follow-up visits and/or perform by telemedicine if possible
    • Delay antiresorptive therapy (zoledronic acid, denosumab) and/or reduce frequency (e.g. every 3 months)

  

Patients with relapsed/refractory MM

High Priority

  • Patients with relapsed disease requiring therapy (development of new SLiM-CRAB criteria or significant paraprotein relapse) or refractory MM:
    • Treatment should not be postponed
    • Therapeutic decisions should be made on a case-by-case basis, considering disease stage, risk, cytogenetics/FISH, age, comorbidities
    • Consider G-CSF support to minimise risk of neutropaenia

Medium Priority

  • Patients with relapsed/refractory disease on continuous treatment:
    • In patients responding to lenalidomide/dexamethasone, consider modifying the treatment regimen to minimise need for clinic/hospital visits, e.g. by:
      • using weekly instead of biweekly administration of drugs (e.g. carfilzomib, bortezomib)
      • preference for oral agents (i.e. ixazomib, lenalidomide, pomalidomide)
      • switching to monthly administration of daratumumab as soon as possible

 Low Priority

  • Patients with relapsed/refractory disease in stable remission on continuous treatment:
    • Delay antiresorptive therapy (zoledronic acid, denosumab) and/or reduce frequency (e.g. every 3 months)

 

Patients with SMM or MGUS

High Priority

-

Medium Priority

  • Consider delaying scheduled visits or reducing clinic visits for surveillance of patients with high-risk SMM (individualised decision according to risk) and/or perform scheduled visits particularly for surveillance by telemedicine and local lab tests if possible

 Low Priority

  • Delay scheduled visits for patients with low risk SMM or MGUS and/or perform by telemedicine and local lab tests if possible

 

*adapted from recommendations made by the International Myeloma Society

 

List of abbreviations: ASCT, autologous stem cell transplantation; FISH, fluorescent in situ hybridisation; G-CSF, granulocyte colony-stimulating factor; IVIg, intravenous immunoglobulin; MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma; OS, overall survival; SMM, smouldering multiple myeloma; Tx, treatment.

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