- Regarding smoldering multiple myeloma (SMM):
- Standard-risk patients should be monitored without active intervention, as usual.
- For high-risk patients, the possibility of enrollment in clinical trials might be limited; consider a conservative approach with close monitoring and observation.
- Regarding newly diagnosed active multiple myeloma (MM):
- All patients should be screened for COVID-19 before starting induction therapy. For patients testing positive, we recommend holding treatment until viral clearance; metabolic and bone-related acute complications should be managed with supportive care.
- For surveillance and follow-up, telemedicine should replace most routine in-clinic visits, and consider decreasing the frequency of lab work as much as possible; in patients with good bone marrow reserve, blood counts could be done blood counts could be done before starting the next cycle rather than weekly.
- Induction therapy for standard-risk patients:
- Consider oral therapy regimens to limit hospital exposure. Ixazomib, lenalidomide and dexamethasone (IRd) or cyclophosphamide, lenalidomide and dexamethasone (CRd) given over 28- day cycles could be appropriate options.
- Consider dose reductions of dexamethasone (20 mg p.o. weekly). For patients who achieve sustained very good partial response or better (≥VGPR) after 3 to 4 cycles, dexamethasone dosing could be further decreased to 12 mg, with adequate monitoring of response.
- Another regimen alternative is daratumumab, lenalidomide and dexamethasone (DRd) given over a 28-day cycle. Full doses of daratumumab and lenalidomide should be given. Dexamethasone should be given orally, to reduce total time in the chemotherapy unit for the patient, and the first dose should be 40 mg to minimize the risk of daratumumab infusion-related reaction; if no infusion reaction occurs, the doses of dexamethasone can be reduced during subsequent cycles and the interval for daratumumab infusion can be decreased to 90 min. In patients who sustain deep responses (≥VGPR) after the second cycle, consider reducing the frequency of administration of daratumumab to every 4 weeks (rather than every 2 weeks), while maintaining cycle length at 28 days.
- Standard of care therapy using lenalidomide, bortezomib and dexamethasone (RVd) should be considered when other options are not available. Bortezomib should be administered subcutaneously, once weekly. The same applies for cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in countries where it is the only approved combination for initial therapy. The frequency of administration of bortezomib can be decreased to every other week in patients who maintain sustained ≥VGPR after 6 to 8 cycles, if the concerns regarding COVID-19 persist.
- If the goals of therapy are achieved after 10 to 12 cycles, consider transitioning to maintenance therapy with lenalidomide.
- Induction therapy for high-risk patients:
- The authors believe such patients have a greater risk of morbidity from myeloma than from a nosocomial COVID-19 infection, hence justifying weekly clinic visits for treatment.
- Consider carfilzomib, lenalidomide and dexamethasone (KRd) given over a 28-day cycle with once-weekly dosing. Reduce the dose of carfilzomib if a patient’s limited bone marrow reserve raises concerns regarding cytopenias.
- Again, consider initial dose reduction of dexamethasone, and further reduction after 4 to 6 cycles if sustained deep responses (≥VGPR) are achieved.
- If KRd is not available, consider using RVd as above.
- Consider decreasing the frequency of proteasome inhibitors’ administration to every other week in patients with sustained response.
- Following 10 to 12 cycles of uninterrupted triplet therapy, consider maintenance therapy with a proteasome inhibitor (weekly ixazomib or bortezomib subcutaneously every 2 weeks).
- These patients should undergo ASCT as soon as the pandemic resolves.
- Induction therapy for frail/non-transplant-eligible patients:
- The authors recommend opting for DRd, if available.
- Other options such as IRd (preferred), CRd, RVd or CyBorD can also be considered.
- Close monitoring is recommended, since such patients frequently require dose adjustments.
- Autologous stem cell transplantation (ASCT) after induction:
- Screening for COVID-19 should be done before ASCT in all patients.
- For standard-risk and high-risk patients who are responding to therapy, consider delaying ASCT until the epidemic subsides; continued induction therapy can safely be used as a bridge. There are no major concerns in delaying stem cell collection, and it should be considered most patients, particularly those with recent COVID-19 infection.
- For patients who are not responding to induction therapy or whose disease is progressing quickly, ASCT should be considered as salvage therapy.
- For ultra-high-risk patients (i.e. with plasma cell leukemia), induction therapy followed without delay by ASCT should be prioritized, as the risk of progressive disease is high.
- Supportive management:
- Immunomodulatory drugs increase the risk of venous thromboembolism and require coadministration of prophylactic anticoagulation; aspirin is sufficient for patients with none or few risk factors for venous thromboembolism, while other forms of anticoagulation are recommended in higher-risk patients.
- Prophylaxis against varicella-zoster virus with acyclovir is required for patients on proteasome inhibitors.
- For Pneumocystis jirovecii prophylaxis, favor use of trimethoprim-sulfamethoxazole; if a patient cannot safely receive sulfa, opt for a prophylaxis other than pentamidine, as its administration is aerosolized and requires a clinic visit.
- Consider delaying bone disease prophylaxis, especially in patients without active bone disease; if a prophylactic agent is used, favor administration every three months rather than monthly. If a patient has diffuse bone disease or hypercalcemia, consider using zoledronic acid. As usual, patients should be advised to take calcium and vitamin D.
- For the management of cytopenias, avoid using growth factors; for neutropenic patients requiring treatment, consider using pegfilgrastim.
- Regarding stable multiple myeloma on maintenance therapy:
- Patients who are stable on maintenance therapy and who tolerate it should continue treatment.
- Most of these patients do not require to be evaluated in-clinic monthly by their physician; monitoring via minimal lab work and telemedicine for toxicity checks could be appropriate.
- In patients whose maintenance regimen includes dexamethasone, consider tapering it down with the goal of discontinuing it.
- Regarding progressing/relapsing multiple myeloma:
- A majority of MM patients will eventually relapse; the management of these patients should be individualized.
- In relapsing patients who did not receive daratumumab for their induction therapy, consider daratumumab-based regimens; recommendations regarding adjustments in dosing and frequency of administration can be applied as described above for newly diagnosed patients.
- If daratumumab is not available, other triplet combinations should be used depending on availability, fitness of the patient and type of maintenance therapy.
- Consider delaying ASCT until resolution of the current pandemic in most patients; salvage ASCT should be considered in standard-risk patients who are not responding adequately to conventional therapy, and in high-risk patients with aggressive relapse showing suboptimal responses to salvage therapy.
- Patients with secondary plasma cell leukemia (ultra-high risk) should receive myeloma-directed therapy followed by ASCT.
The authors provide a framework of recommendations to assist physicians in optimizing the care of multiple myeloma patients in the setting of current pandemic; their suggestions are not evidence based, as limited data is available, but may guide hematologists/oncologists in their clinical decision-making and in determining case priorities in patients dealing with MM.
Source:
- Al Saleh A.S., Sher T. and Gertz M.A. (April 17, 2020). Multiple Myeloma in the Time of COVID-19. Acta Haematologica. https://doi.org/1159/000507690