T-cell-engaging bispecific antibodies in cancer

Donk, Niels W.C.J. van de

doi:10.1016/s0140-6736(23)00521-4

Cited by 88 publications

(30 citation statements)

References 122 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…Individual assessment of appropriate prophylaxis (and management) should be made per institutional guidelines and other published recommendations. 1,28,[30][31][32] Based on the infection profile of teclistamab, prophylaxis for PJP and HSV/VZV is recommended for all patients. In MajesTEC-1, 3/7 patients with PJP and 4/6 patients with HSV or herpes zoster were receiving prophylaxis at the time of infection, indicating that other factors could be affect infection risk; these remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Nooka,

Rodriguez,

Mateos

et al. 2023

Cancer

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BackgroundPatients with relapsed/refractory multiple myeloma are at increased risk of infection. Infections during treatment with teclistamab, the first B‐cell maturation antigen‐directed bispecific antibody approved for triple‐class–exposed relapsed/refractory multiple myeloma, was examined in the phase 1/2 MajesTEC‐1 study.MethodsPatients (N = 165) received subcutaneous teclistamab 1.5 mg/kg weekly after a step‐up dosing schedule (0.06 mg/kg and 0.3 mg/kg, each separated by 2–4 days). Patients were monitored frequently for infections; prophylaxis and management were per institutional guidelines.ResultsAt a median follow‐up of 22.8 months (range, 0.3–33.6), infections were reported in 132 patients (80.0%). Grade 3/4 infections occurred in 91 patients (55.2%), including COVID‐19 (21.2%), respiratory infections (19.4%), Pneumocystis jirovecii pneumonia (4.2%), viral infections (4.2%), and gastrointestinal infections (1.2%). Twenty‐one patients died from infections (18 from COVID‐19). Median time to first onset of any‐grade and grade 3 to 5 infections was 1.7 and 4.2 months, respectively. Overall, 70.9% of patients had ≥1 postbaseline immunoglobulin G (IgG) level <400 mg/dL; median time to IgG <400 mg/dL was 1.2 months (range, 0.2–19.8) and 46.1% received ≥1 dose of IgG replacement. Grade 3/4 neutropenia occurred in 65.5% of patients (median time to grade ≥3 neutropenia/febrile neutropenia was 2.3 months [range, 0–18.1]).ConclusionBased on the infection profile of B‐cell maturation antigen–targeted bispecific antibodies such as teclistamab, it is recommended that clinicians and patients remain vigilant for a range of infection types throughout treatment to facilitate prompt intervention. Appropriate screening, prophylaxis, and management of infections, hypogammaglobulinemia, and neutropenia are important.Clinical trial registrationNCT03145181/NCT04557098 (ClinicalTrials.gov)Plain Language Summary Before starting teclistamab, patients should be up to date with vaccinations (including COVID‐19) and screened for hepatitis B and C and HIV. Teclistamab should not be given to patients with any active infections. Prophylactic antimicrobials should be administered per institutional guidelines. Prophylaxis for Pneumocystis jirovecii pneumonia and herpes simplex/varicella zoster virus is recommended during teclistamab treatment. Close monitoring of infections and immunoglobulin G (IgG) levels should continue throughout teclistamab treatment. IgG replacement (administered every 3–6 weeks) should be used to maintain IgG ≥400 mg/dL. Growth factors should be considered for grade ≥3 neutropenia with infection/fever and grade 4 neutropenia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Nooka,

Rodriguez,

Mateos

et al. 2023

Cancer

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“…Nora et al discovered that treatment-free intervals could interrupt the sustained stimulation of T cells by antibodies, thereby amplifying T cell functionality and inducing transcriptional reprogramming [ 278 ]. Targeting the PD-1/PD-L1 signaling pathway or exploring the targeting of co-stimulatory or co-inhibitory receptors, has been shown to mitigate T-cell exhaustion [ 186 , 279 ]. Studies have demonstrated that the blockade of the PD-1/PD-L1 pathway facilitates the lysis of AML cells by CD33/CD3 BSABs [ 280 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison

Cheng,

Chen,

Shi

et al. 2024

Mol Cancer

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Emerging tumor immunotherapy methods encompass bispecific antibodies (BSABs), immune checkpoint inhibitors (ICIs), and adoptive cell immunotherapy. BSABs belong to the antibody family that can specifically recognize two different antigens or epitopes on the same antigen. These antibodies demonstrate superior clinical efficacy than monoclonal antibodies, indicating their role as a promising tumor immunotherapy option. Immune checkpoints are also important in tumor immunotherapy. Programmed cell death protein-1 (PD-1) is a widely acknowledged immune checkpoint target with effective anti-tumor activity. PD-1 inhibitors have demonstrated notable therapeutic efficacy in treating hematological and solid tumors; however, more than 50% of patients undergoing this treatment exhibit a poor response. However, ICI-based combination therapies (ICI combination therapies) have been demonstrated to synergistically increase anti-tumor effects and immune response rates. In this review, we compare the clinical efficacy and side effects of BSABs and ICI combination therapies in real-world tumor immunotherapy, aiming to provide evidence-based approaches for clinical research and personalized tumor diagnosis and treatment.

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“…Central to their dual-specific functionality is the ability to directly steer T cells towards tumor cells, thus enhancing T cell-mediated identification and elimination of tumor cells. A distinctive feature of BsAbs-induced tumor cell lysis is its independence from conventional antigen recognition processes, which typically involve MHC class I or II molecules, antigen-presenting cells, or the necessity of co-stimulatory molecules ( 167 ).…”

Section: Therapeutic Strategies For Cold Tumorsmentioning

confidence: 99%

Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors

Ouyang,

Wang,

et al. 2024

Front. Immunol.

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Immune Checkpoint Inhibitors (ICIs) therapy has advanced significantly in treating malignant tumors, though most ‘cold’ tumors show no response. This resistance mainly arises from the varied immune evasion mechanisms. Hence, understanding the transformation from ‘cold’ to ‘hot’ tumors is essential in developing effective cancer treatments. Furthermore, tumor immune profiling is critical, requiring a range of diagnostic techniques and biomarkers for evaluation. The success of immunotherapy relies on T cells’ ability to recognize and eliminate tumor cells. In ‘cold’ tumors, the absence of T cell infiltration leads to the ineffectiveness of ICI therapy. Addressing these challenges, especially the impairment in T cell activation and homing, is crucial to enhance ICI therapy’s efficacy. Concurrently, strategies to convert ‘cold’ tumors into ‘hot’ ones, including boosting T cell infiltration and adoptive therapies such as T cell-recruiting bispecific antibodies and Chimeric Antigen Receptor (CAR) T cells, are under extensive exploration. Thus, identifying key factors that impact tumor T cell infiltration is vital for creating effective treatments targeting ‘cold’ tumors.

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T-cell-engaging bispecific antibodies in cancer

Cited by 88 publications

References 122 publications

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

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

Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison

Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors

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