Teclistamab in Combination with Subcutaneous Daratumumab and Lenalidomide in Patients with Multiple Myeloma: Results from One Cohort of MajesTEC-2, a Phase1b, Multicohort Study

Searle, Emma; Quach, Hang; Wong, Sandy W.; Costa, Luciano J.; Hulin, Cyrille; Janowski, Wojciech; Berdeja, Jesús G.; Anguille, Sébastien; Matous, Jeffrey; Touzeau, Cyrille; Michallet, Anne‐Sophie; Husnik, Marla; Vishwamitra, Deeksha; Niu, Zhuolu; Larsen, Julie S.; Goldberg, Jenna D.; Popat, Rakesh; Spencer, Andrew

doi:10.1182/blood-2022-159711

Cited by 42 publications

(27 citation statements)

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“…These data support combining BsAbs with IMiDs and CELMoDs. Initial results from the phase 1b MajesTEC-2 study of teclistamab with daratumumab and lenalidomide in RRMM have shown promising results with an ORR of 90% and an acceptable safety profile [ 59 ]. There are currently several ongoing studies investigating various combinations, as shown in Table 2 .…”

Section: Imidsmentioning

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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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: Imidsmentioning

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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“…The 0.72 mg/kg dose produced a VGPR or better in 12 patients. Results from the 1.5 mg/kg dose group were not mature 29 …”

Section: Ongoing Clinical Studiesmentioning

confidence: 90%

Teclistamab‐cqyv in multiple myeloma

Martino,

Bruzzese,

Labanca

et al. 2023

European J of Haematology

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Multiple myeloma (MM) is an incurable neoplasm characterized by significant morbidity and mortality. Despite advances in treatment, MM patients eventually experienced a relapse of the disease. Penta‐drug refractory patients continue to be the hard core of relapsed/refractory (RR) settings. Teclistamab‐cqyv is a humanized IgG4 antibody and a bispecific BCMA‐director CD3 T‐cell engager. It recruits endogenous T cells, by targeting CD3 receptors expressed on their surface, resulting in their activation against BCMA, an antigen expressed by plasma cells. US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved Teclistamab‐cqyv in monotherapy for the treatment of RRMM patients who have received at least three prior therapies, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and anti‐CD38 monoclonal antibodies (MoAbs) and have demonstrated disease progression during the last therapy. Its effectiveness was demonstrated in a pivotal clinical trial where the overall response rate (ORR) reached 60%. Other clinical studies are currently ongoing to investigate the association of the bispecific antibody with novel drugs with encouraging preliminary results, especially in the setting of heavily pretreated patients. In this review, the authors will provide a comprehensive overview of the drug, including its mechanism of action, major clinical trials, and future perspectives.

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“…Teclistamab is a novel bispecific antibody targeting both BCMA and CD3 that has demonstrated remarkable efficacy as monotherapy in triple-class exposed MM and in combination with daratumumab and lenalidomide in heavily pretreated patients. 51,52 The MajesTEC-4 (EMN30) study aims to enrol 1000 patients and randomise them to either combination teclistamab and lenalidomide maintenance or single agent lenalidomide in patients post-AHCT. Immunomodulatory agents have been proposed to improve the efficacy of immunotherapy and it is anticipated this combination may further improve efficacy.…”

Section: Teclistamabmentioning

confidence: 99%

The role of maintenance therapy following autologous stem cell transplantation in newly diagnosed multiple myeloma: Considerations on behalf of the Chronic Malignancies Working Party of the EBMT

Hwang,

Hayden,

Pawlyn

et al. 2024

Br J Haematol

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SummaryRecent treatment advancements in multiple myeloma have led to significant improvements in patient outcomes. Maintenance therapy following autologous haematopoietic stem cell transplantation (AHCT) is now standard of care and has been demonstrated to prolong and deepen treatment responses. Currently, lenalidomide remains the single agent that has been approved for maintenance post‐AHCT in Europe and the USA which, if tolerated, is continued until disease progression. The treatment landscape is rapidly expanding however, and the optimal personalised maintenance approach for a patient is becoming more complex. Treatment outcomes for patients with high‐risk disease remain poor and choice of maintenance in this population also remains unclear. This review article evaluates up‐to‐date literature regarding established maintenance approaches. It further analyses ongoing studies exploring maintenance regimens using combination and novel agents, approaches to maintenance in patients with cytogenetic high‐risk disease and minimal residual disease response‐adapted strategies that reflect the current evolving treatment paradigm.

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Teclistamab in Combination with Subcutaneous Daratumumab and Lenalidomide in Patients with Multiple Myeloma: Results from One Cohort of MajesTEC-2, a Phase1b, Multicohort Study

Cited by 42 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

Teclistamab‐cqyv in multiple myeloma

The role of maintenance therapy following autologous stem cell transplantation in newly diagnosed multiple myeloma: Considerations on behalf of the Chronic Malignancies Working Party of the EBMT

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