In retrospect, these guidelines remain useful for personalized myeloma treatment

The novel coronavirus pneumonia (COVID-19) pandemic has created significant challenges in the clinical management of multiple myeloma (MM) patients
.
Not only the present but also the future
.

COVID-19 (COVID-19) seems like an old topic, after all, it's been nearly three years in
popularity.
In the round of "disturbance", the doctor's diagnosis and treatment and the patient's visit behavior are in a routine-unconventional state transition
.
COVID-19 has become an important dividing line in addition to the disease itself, the patient's economic condition, drug access, and more
.

In fact, since the beginning of the COVID-19 epidemic, the European Myeloma Network (EMN), the European Society for Internal Oncology (ESMO), and the ESMO-European Hematology Association (EHA) International Multidisciplinary Expert Group have all made relevant recommendations
for MM.
Even now, it is still useful for clinicians, after all, so far, the personalized management of MM patients still needs to add this item
.

MM management decision path at a glance

For the management of MM patients during the COVID-19 pandemic, EMN gives detailed recommendations, as shown in Figure 1^[1].

(Click to enlarge)

Figure 1 "Decision-making algorithm for MM patient management during the COVID-19 epidemic" proposed by EMN

ESMO's recommendations for the personalized management of MM are divided into different levels

For the management and treatment of MM patients during the COVID-19 pandemic, ESMO recommends intervention with 3 priorities, namely high-priority, medium-priority, and low-priority ^[2], as follows:

01Recommended

high priority for young, transplant-appropriate graded interventions

Newly diagnosed active/high-risk patients (presence of SLiM-CRAB):

• Treatment should not be postponed

• Treatment decisions should be made after specific analysis of disease stage, risk, age, cytogenetics/FISH, and comorbidities, taking into account

• Consider G-CSF support to minimize the risk of neutropenia

Medium priority

Patients receiving ongoing first-line therapy:

• Consider delaying ASCT and extending the induction protocol to 6 to 8 cycles

• For patients scheduled to receive ASCT, they should be tested for COVID-19 prior to ASCT

• For patients at standard risk, delayed ASCT through additional cycles of induction therapy and/or lenalidomide maintenance therapy may be considered (early treatment in this case has not demonstrated overall survival benefit compared with "three-drug regimen induction of sequentialonimide maintenance without ASCT consolidation")

• Where possible, use telephone and/or virtual appointments to monitor treatment tolerance to reduce the number of clinical visits

• For patients receiving maintenance therapy, consideration may be given to extend the use of nadodomide to 2 months in the future (during telemedicine/remote laboratory testing)

• In patients requiring intravenous immunoglobulin (IVIg) replacement therapy, consideration is given to reducing the frequency of administration

• Consider G-CSF support to minimize the risk of neutropenia

Low priority

Patients in stable remission (not currently receiving aggressive treatment):

• If possible, delayed follow-up and/or through telemedicine

• Delay anti-bone resorption therapy (zoledronic acid, denosumab) and/or reduce the frequency of administration (e.
  g.
  , every 3 months)

02 Recommended

high priority for graded interventions in elderly patients with newly diagnosed MM who are not suitable for transplantation

Patients with newly diagnosed active/high-risk disease (in the presence of SLiM-CRAB):

• Treatment should not be postponed

• Treatment decisions should be made after specific analysis of disease stage, risk, age, cytogenetics/FISH, and comorbidities, taking into account

• Consider G-CSF support to minimize the risk of neutropenia

Medium priority

Patients receiving ongoing treatment:

• In patients who respond to Rd therapy, discontinuation of dexamethasone and use of nalide monotherapy to maintain the response should be considered

• Oral prescription medications available are preferred

• If parenteral administration is required, consider reducing the frequency of use

• Use phone and/or virtual appointments to monitor tolerance and treatment outcomes whenever possible

• Reduce the dose of dexamethasone to ≤ 20 mg / week

• Consider G-CSF support to minimize the risk of neutropenia

Low priority

Patients receiving steady remission with ongoing treatment (or not receiving aggressive treatment):

• If possible, delayed follow-up and/or through telemedicine

• Delay anti-bone resorption therapy (zoledronic acid, denosumab) and/or reduce the frequency of administration (e.
  g.
  , every 3 months)

03Hierarchical intervention is recommended for patients with relapsed/refractory MM with

high priority

Patients with recurrent or refractory MM who require treatment:

• Treatment should not be postponed

• Treatment decisions should be made after specific analysis, taking into account disease stage, risk, cytogenetics/FISH, age, and comorbidities

• Consider G-CSF support to minimize the risk of neutropenia

Medium priority

Patients with relapsed/refractory MM receiving ongoing therapy:

In patients who respond to Rd therapy, consider modifying the treatment plan to minimize clinical/hospital visits, such as:

• Replace 2 weekly dosages with once-weekly dosing (eg, carfezomib, bortezomib)

• Preferred oral medication (eg, isazomib, lenalidomide, pomadomide)

• Switch to daretuzumab for monthly administration as soon as possible

Low priority

Patients with relapsed/refractory MM who receive stable remission from ongoing therapy:

• Delay anti-bone resorption therapy (zoledronic acid, denosumab) and/or reduce the frequency of administration (e.
  g.
  , every 3 months)

04 Recommended

high-priority medium-priority
for hierarchical interventions in patients with monoclonal immunoglobulin hyperplasia (MGUS) or smoke-emitting MM (SMM) of unknown significance

-

• For monitoring of patients with high-risk SMM, consider delaying scheduled visits or reducing clinical visits (individualized decisions based on risk) and/or where possible implementing scheduled visits through telemedicine and local laboratory testing for monitoring

Low priority

• For patients with low-risk SMM or MGUS, scheduled visits are delayed and/or performed through telemedicine and, where possible, local laboratory testing

ESMO-EHA Interdisciplinary Expert Consensus: 6 Recommendations


on MM 01 When Must Myeloma Treatment Be Initiated During an Outbreak, Released in 2022?

Treatment should not be delayed in newly diagnosed MM patients with active disease and in cases requiring urgent treatment
.
Patients with end-organ damage due to hypercalcemia, renal failure, anemia, and bone disease (CRAB) should be treated as soon as possible, but treatment
can be appropriately delayed for a limited time if MM patients present in a disease or meet SLiM criteria in the community at high risk of epidemic transmission.

Patients with isolated plasma cell tumor as the only indication may initially receive only local radiotherapy
.
Patients with MGUS or SMM usually have long-term monitoring of disease status
.

02How to treat MM patients who do not have new coronavirus symptoms or have mild symptoms?

For MM patients with a positive SARS-CoV-2 PCR test but without COVID-19 symptoms, 14-day isolation should be considered if MM-related events allow delayed anti-myeloma therapy; Otherwise, treatment should be given and symptoms should be closely monitored for early detection of COVID-19 disease progression
.
For symptomatic patients with COVID-19, antimyeloma therapy should be postponed until clinical recovery
from COVID-19.

03Is first-line anti-myeloma treatment appropriate/inappropriate for transplant patients during the epidemic?

The preferred induction regimen for transplant patients is bortezomib, dexamethasone plus lenalidomide (VRd), or thalidomide (VTD), and daretoluzumab plus VTD (DaraVTD), and patients with adequate response may be adjusted
.
Patients at high risk can receive ASCT, while patients at marked risk may postpone ASCT, depending on the COVID-19 situation in the community, but try not to exceed 3 months
.

Suitable regimens for transplant patients include VRd or daretosuzumab-based therapy [Darard (daretoulumab, lenalidomide, dexamethasone) or DaraVMP (daretoulumab, bortezomib, mevalen, prednisone)].

In high-risk communities, a full oral regimen can be administered, followed by bortezomib or daretuzumab
if the response is ineffective.
In general, the number of visits to the hospital should be minimized, for example, to remission patients without affecting treatment
outcomes.

04Should MM maintenance regimens be adjusted during the epidemic?

Patients with MM in the maintenance phase should continue oral therapy and reduce the number of visits
.

05Should treatment strategies for patients with relapsed MM be changed during the epidemic?

Patients with symptomatic relapse of MM should not delay treatment
.
Prefer oral regimens that respond equally well to those that require frequent hospital visits
.
Alternatively, low-intensity administration of intravenous, subcutaneous drugs is performed
.
Also, avoid salvage transplantation
.

06Is cell therapy such as ASCT or CAR-T treatment postponed during the pandemic?

In high-risk communities, patients with mark-risk MM can delay early ASCT, while high-risk MM patients continue
.
Patients who are eligible for a clinical trial of CAR-T therapy and have no other treatment options may continue to participate in the trial
.
If ASCT or CAR-T treatment cannot be postponed according to the doctor's judgment, it is necessary to rule out COVID-19 by PCR testing for SARS-CoV-2, while taking strict precautions in the transplant department to prevent the spread of SARS-CoV-2^[3].

References

[1] Terpos E, Engelhardt M, Cook G, et al.
Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN)[J].
Leukemia.
2020 Aug; 34(8):2000-2011.

[2] ESMO MANAGEMENT AND TREATMENT ADAPTED RECOMMENDATIONS IN THE COVID-19 ERA: MULTIPLE MYELOMA

Buske C, Dreyling M, Alvarez-Larrán A, et al.
Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus[J].
ESMO Open.
2022 Apr; 7(2):100403.

Material approval number: VV-MEDMAT- 74284

Material approval date: 9/2022

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