Monitoring, prophylaxis, and treatment of infections in patients with MM receiving bispecific antibody therapy: consensus recommendations from an expert panel

Abstract

Bispecific antibodies (BsAbs) are emerging as an important novel class of immunotherapeutic agents for the treatment of multiple myeloma (MM), and are set to be more widely used in clinical practice. However, this new class of therapies is associated with a distinct adverse event (AE) profile that includes cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as AEs leading to increased infection risk such as cytopenias and hypogammaglobulinemia, and infections themselves. As preliminary data with this class of agents shows an increased risk of infections as compared with conventional MM treatment regimens, such as immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies (mAbs), guidance on infection monitoring, prophylaxis and treatment is required. This review provides consensus recommendations from a panel of 13 global experts, following a meeting in August 2022. The meeting objective was to review existing literature and identify relevant information on infections with all BsAbs in patients with MM, as well as to discuss clinical experience of experts in managing these infections. The recommendations outlined here can be used to guide management of infection risk factors, such as hypogammaglobulinemia and neutropenia. In addition, they can be used to guide the monitoring, prophylaxis, and treatment of bacterial, viral and fungal infections, including emerging infections of interest, such as coronavirus 2019 (COVID-19), and the use of vaccinations prior to and during BsAb treatment. The recommendations have been graded by the panel based on level of data available. Key recommendations include universal herpes simplex and varicella zoster virus prophylaxis, screening for hepatitis B virus reactivation risk in all patients, monthly intravenous immunoglobulin treatment for immunoparesis and in the absence of life-threatening infectious manifestations, use of colony-stimulating factors in patients with Grade 3 neutropenia, universal pneumocystis jirovecii pneumonia prophylaxis and no routine anti-fungal prophylaxis.

Incidence, timing, and management of infections in patients receiving teclistamab for the treatment of relapsed/refractory multiple myeloma in the MajesTEC‐1 study

“…Based on our experience, we have identified several recommendations for the management of potential infections from a clinical practice perspective, in line with the teclistamab prescribing information (Table S5) and other recently published guidance. 1,[28][29][30][31][32][33] Before starting teclistamab, patients should not have any active infections and should be screened for HBV, HCV, and HIV. Immunosuppressive therapy is associated with a high risk of HBV reactivation 43 ; alongside appropriate prophylaxis, 1 screening may prevent potentially serious complications.…”

“…25 To ensure the appropriate management of specific adverse events (AEs) identified as posing a potential risk to patients receiving teclistamab, including serious infections, a Risk Evaluation and Mitigation Strategy is ongoing in the United States and a Risk Management Plan is in place in the European Union. 26,27 To build on recently published consensus recommendations 1,28,29 and other relevant guidance [30][31][32][33] on managing infections with bispecific antibodies, we undertook a detailed analysis of MajesTEC-1 to provide recommendations for prevention and management of potential infections during teclistamab treatment.…”

Bispecific antibodies for the treatment of relapsed/refractory multiple myeloma: updates and future perspectives

“…Among the 26 patients who responded to anti-BCMA bispecific antibody therapy, profound hypogammaglobulinemia occurred in 100% and receiving IVIG lowered the rate of a ≥grade 3 infection by 90% ( 101 ). Efforts and recommendations to mitigate infections with bispecific antibody treatment are ongoing ( 102 ).…”

Supportive care measures for bispecific T-cell engager therapies in haematological malignancies

“…Antibody responses in patients on immune therapies may increase with sequential vaccinations or boosters [45,46]. Recent guidelines recommend antiviral prophylaxis against HSV and VZV, intravenous immunoglobulin for patients with IgG levels ≤400 mg/dL, and antibiotic prophylaxis in high-risk patients [27 ▪ ,47]. Fungal prophylaxis should be considered in patients with prolonged neutropenia or those subjected to prolonged courses of steroid treatment.…”

“…Fungal prophylaxis should be considered in patients with prolonged neutropenia or those subjected to prolonged courses of steroid treatment. Given the 3–4% risk of grade ≥3 PCP infection with BCMA-targeting TCEs, some guidelines recommend routine PCP prophylaxis with co-trimoxazole [47]. Close monitoring for infections is important, and a high index of suspicion for opportunistic infections is needed to facilitate timely treatment.…”