EMN recommendations for COVID-19 vaccination in patients with MM

Multiple myeloma (MM) and other monoclonal gammopathies can increase patient susceptibility to infection, either as a direct result of disease characteristics and comorbidities, or treatment-mediated immune suppression. With regard to the COVID-19 pandemic, this can translate to prolonged infection and an increased risk of mortality following infection with SARS-CoV-2.¹ In a recent podcast, Michel Delforge and Noopur Raje highlighted the increased vulnerability of patients with MM to infections, including COVID-19.  

Historically, patients with MM also demonstrate suboptimal vaccine-mediated antibody responses. As a result, a number of studies are evaluating anti-SARS-CoV-2 antibody perseverance in patients with MM following infection and vaccination. Although ongoing, data from these studies suggest a suboptimal SARS-CoV-2 antibody response in patients with MM, highlighting a need for close monitoring and clinical management.¹

In contrast to MM, data from the iStopMM study (N = 75,422) suggest that monoclonal gammopathy of undetermined significance (MGUS) is not associated with an increased risk of SARS-CoV-2 infection and COVID-19 severity. This important finding highlights immune response variation between patients with MM and MGUS, influencing guidelines on the treatment and management of these patients moving forward.²

A review by Heinz Ludwig and colleagues¹ consolidated the latest European Multiple Myeloma Network (EMN) consensus guidelines on COVID-19 vaccination in patients with MM, below is a summary.

Treatment

Anti-myeloma treatments, particularly anti-CD38 therapies, can impair patient immune responses. Limiting immunosuppression in patients undergoing treatment for MM and other monoclonal gammopathies has become ever more pressing throughout the COVID-19 era. There are a number of studies evaluating approaches to reduce the risk of severe COVID-19 disease in these patients, including over 560 clinical trials evaluating active treatments for COVID-19. The recommended treatment adaptations and key considerations are outlined in Figures 1 & 2.

Figure 1. Adaptations of treatments for patients with monoclonal gammopathies throughout the COVID-19 pandemic*

ADCs, antibody-drug conjugates; BiTEs, bispecific T-cell engagers; CAR, chimeric antigen receptor; mAb, monoclonal antibody; MM, multiple myeloma.
*Information from Ludwig, et al.¹

Figure 2. Guidelines on the prevention and treatment of COVID-19 in patients with monoclonal gammopathies*

EMA, European Medicines Agency; FDA, U.S. Food and Drug Administration; mAbs, monoclonal antibodies.
*Information from Ludwig, et al.¹

Vaccination

Real-world data suggest that patients with MM are generally willing to receive a COVID-19 vaccine, more so than the general population. The EMN has set out vaccination guidelines for healthcare professionals involved in the treatment and care of patients with MGUS, smoldering multiple myeloma, multiple myeloma, and monoclonal gammopathies of clinical significance (Figure 3). It has been recommended that all patients with these conditions be vaccinated against COVID-19.

The guidelines recognize uncontrolled disease, immunoparesis, >1 previous line of therapy, specific treatment classes, and older age as risk factors for inferior responses to COVID-19 vaccination. Despite not receiving backing from the Centers for Disease Control and Prevention, analyzing patient vaccine responses is crucial to identify those with suboptimal anti-SARS-CoV-2 responses and who might benefit from a third dose.

Figure 3. Guidelines on the vaccination of patients with monoclonal gammopathies against SARS-CoV-2*

ASCT, autologous stem cell transplantation; CR, complete response; EMN, European Multiple Myeloma Network; mAb, monocolonal antibody; MGCS, monoclonal gammopathy of clinical significance; MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma; MRD, measurable residual disease; SMM, smoldering multiple myeloma; VGPR, very good partial response.
*Information from Ludwig, et al.^1
†Lenalidomide maintenance therapy is an exception.
^‡Vaccination should be considered on an individual basis to account for patients with poorly controlled disease undergoing continuous therapy.

Conclusion

The EMN COVID-19 consensus recommendations provide guidance around the vaccination strategy for patients with monoclonal gammopathies. The guidance also covers the treatment and management of both the underlying disease and COVID-19 in these patients, with the aim to reduce the risk of infection, severe disease, and mortality. The Multiple Myeloma Hub was pleased to receive comment from primary author, Heinz Ludwig: