Risk of Infections Associated with the Use of Bispecific Antibodies in Multiple Myeloma: A Pooled Analysis

Mazahreh, Farah; Mazahreh, Liyan; Schinke, Carolina; Thanendrarajan, Sharmilan; Zangari, Maurizio; Shaughnessy, John D.; Zhan, Fenghuang; Rhee, Frits van; Hadidi, Samer Al

doi:10.1182/blood-2022-157858

Cited by 5 publications

(8 citation statements)

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“…A total of 15% of patients developed COVID-19 infection (11% grade 3–4), and opportunistic infections were also seen, including cytomegalovirus infection (CMV) in 4%. Some 49% of the cohort had documented hypogammaglobulinaemia [ 92 ]. Another group reviewed 37 patients treated with an anti-BCMA BsAb.…”

Section: Safetymentioning

confidence: 99%

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Bispecific Antibodies in Multiple Myeloma: Opportunities to Enhance Efficacy and Improve Safety

Swan

Murphy

Glavey

et al. 2023

Cancers

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Multiple myeloma (MM) is the second most common haematological neoplasm of adults in the Western world. Overall survival has doubled since the advent of proteosome inhibitors (PIs), immunomodulatory agents (IMiDs), and monoclonal antibodies. However, patients with adverse cytogenetics or high-risk disease as determined by the Revised International Staging System (R-ISS) continue to have poorer outcomes, and triple-refractory patients have a median survival of less than 1 year. Bispecific antibodies (BsAbs) commonly bind to a tumour epitope along with CD3 on T-cells, leading to T-cell activation and tumour cell killing. These treatments show great promise in MM patients, with the first agent, teclistamab, receiving regulatory approval in 2022. Their potential utility is hampered by the immunosuppressive tumour microenvironment (TME), a hallmark of MM, which may limit efficacy, and by undesirable adverse events, including cytokine release syndrome (CRS) and infections, some of which may be fatal. In this review, we first consider the means of enhancing the efficacy of BsAbs in MM. These include combining BsAbs with other drugs that ameliorate the effect of the immunosuppressive TME, improving target availability, the use of BsAbs directed against multiple target antigens, and the optimal time in the treatment pathway to employ BsAbs. We then discuss methods to improve safety, focusing on reducing infection rates associated with treatment-induced hypogammaglobulinaemia, and decreasing the frequency and severity of CRS. BsAbs offer a highly-active therapeutic option in MM. Improving the efficacy and safety profiles of these agents may enable more patients to benefit from these novel therapies and improve outcomes for patients with high-risk disease.

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Section: Safetymentioning

confidence: 99%

“…The risk of CMV reactivation appears to be significant, and monthly CMV monitoring should be considered. Pneumocystis jiroveci pneumonia (PJP) has rarely been seen [ 92 ], with no clear requirement for PJP prophylaxis currently; however, longer term follow-up of clinical trials and real-world data is eagerly awaited.…”

Section: Safetymentioning

confidence: 99%

Bispecific Antibodies in Multiple Myeloma: Opportunities to Enhance Efficacy and Improve Safety

Swan

Murphy

Glavey

et al. 2023

Cancers

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“…40,41 Additionally, a recent meta-analysis, reported CMV infection and/or reactivation rate of 8% in clinical trials of BsAb. 51 The global COVID-19 pandemic appears to be transitioning to an endemic state and current variants present in the US seem less virulent, but COVID-19 will likely remain a serious threat to cancer patients. In addition to the lack of universal uptake of COVID-19 vaccination, suboptimal vaccines response has been demonstrated in recipients of CAR T-cell and BsAb therapy.…”

Section: Viral Infectionsmentioning

confidence: 99%

“…In a single centre report of 37 patients treated with BCMA BsAb, there were six unusual opportunistic infections including 22% cases of CMV reactivation with two cases of CMV esophagitis 40,41 . Additionally, a recent meta‐analysis, reported CMV infection and/or reactivation rate of 8% in clinical trials of BsAb 51 …”

Section: Infection Prevention Strategiesmentioning

confidence: 99%

Recommendations on prevention of infections during chimeric antigen receptor T‐cell and bispecific antibody therapy in multiple myeloma

et al. 2023

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SummaryChimeric antigen receptor T (CAR T) cell and bispecific antibody therapies have shown unprecedented efficacy in heavily pretreated patients with multiple myeloma (MM). However, their use is associated with a significant risk of severe infections, which can be attributed to various factors such as hypogammaglobulinemia, neutropenia, lymphopenia, T‐cell exhaustion, cytokine‐release syndrome and immune‐effector cell‐associated neurotoxicity syndrome. As these therapies have been recently approved by regulatory agencies, it is crucial to establish practical guidelines for infection monitoring and prevention until robust data from prospective clinical trials become available. To address this issue, a panel of experienced investigators from the Academic Consortium to Overcome Multiple Myeloma through Innovative Trials (COMMIT) developed consensus recommendations for mitigating infections associated with CAR T‐cell and bispecific antibody therapies in MM patients.

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“…A larger pooled analysis of 10 clinical trials of MM BiTEs in 790 MM patients (73% of patients treated with an agent targeting BCMA) showed grade II/IV neutropenia in 37% and grade III/IV infections in 26%. Importantly, non-BCMA targeted BiTEs were associated with lower grade II/IV neutropenia (45.6% vs. 24.4%) and lower grade III/IV infections (27.5% vs. 16.9%) when compared to BCMA BiTEs 11 .…”

mentioning

confidence: 93%

Protracted viral infections in patients with multiple myeloma receiving bispecific T-cell engager therapy targeting B-cell maturation antigen

et al. 2023

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Risk of Infections Associated with the Use of Bispecific Antibodies in Multiple Myeloma: A Pooled Analysis

Cited by 5 publications

References 0 publications

Bispecific Antibodies in Multiple Myeloma: Opportunities to Enhance Efficacy and Improve Safety

Bispecific Antibodies in Multiple Myeloma: Opportunities to Enhance Efficacy and Improve Safety

Recommendations on prevention of infections during chimeric antigen receptor T‐cell and bispecific antibody therapy in multiple myeloma

Protracted viral infections in patients with multiple myeloma receiving bispecific T-cell engager therapy targeting B-cell maturation antigen

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