Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study

Usmani, Saad Z.; Garfall, Alfred L.; Donk, Niels W.C.J. van de; Nahi, Hareth; Miguel, Jesús F. San; Oriol, Albert; Rosiñol, Laura; Chari, Ajai; Bhutani, Manisha; Karlin, Lionel; Benboubker, Lotfi; Pei, Lixia; Verona, Raluca; Girgis, Suzette; Stephenson, Tara; Elsayed, Yusri; Infante, Jeffrey R.; Goldberg, Jenna D.; Banerjee, Arnob; Mateos, María‐Victoria; Krishnan, Amrita

doi:10.1016/s0140-6736(21)01338-6

Cited by 172 publications

(161 citation statements)

References 19 publications

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“…The drug was well tolerated with no high-grade Cytokine Release Storm (CRS), and self-limited cytopenias. Given confirmatory results in the phase II extension of this trial teclistamab is likely to become the first bispecific antibody approved for the therapy of RRMM [46]. Further trials examining teclistamab in earlier lines of therapy are planned.…”

Section: Antibody Drug Conjugates (Adcs)mentioning

confidence: 83%

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Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond

Podar

Leleu

2021

Cancers

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Despite the challenges imposed by the COVID-19 pandemic, exciting therapeutic progress continues to be made in MM. New drug approvals for relapsed/refractory (RR)MM in 2020/2021 include the second CD38 monoclonal antibody, isatuximab, the first BCMA-targeting therapy and first-in-class antibody–drug conjugate (ADC) belantamab mafodotin, the first BCMA-targeting CAR T cell product Idecabtagen-Vicleucel (bb2121, Ide-Cel), the first in-class XPO-1 inhibitor selinexor, as well as the first-in-class anti-tumor peptide-drug conjugate, melflufen. The present introductory article of the Special Issue on “Advances in the Treatment of Relapsed and Refractory Multiple Myeloma: Novel Agents, Immunotherapies and Beyond” summarizes the most recent registration trials and emerging immunotherapies in RRMM, gives an overview on latest insights on MM genomics and on tumor-induced changes within the MM microenvironment, and presents some of the most promising rationally derived future therapeutic strategies.

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Section: Antibody Drug Conjugates (Adcs)mentioning

confidence: 83%

“…Being available "off-the-shelf", BiTEs but also ADCs represent community practice-friendly choices, for patients with rapid disease progression in particular. Nevertheless, in contrast to CAR T cells, an intensive treatment schedule is required for these modalities, thereby challenging the patient's QoL [34,46].…”

Section: Antibody Drug Conjugates (Adcs)mentioning

confidence: 99%

Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond

Podar

Leleu

2021

Cancers

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“…Frequency and severity of CRS depend on the therapeutic agent. In patients treated with T-BsAbs the incidence of CRS ranges from 40 to 70%, and intensity is usually mild to moderate [151,154]. On the contrary, treatment with CAR-T cells is complicated by CRS in almost 90% of the patients, and 7 to 30% may experience grade 3 or worse toxicity [149,155].…”

Section: Discussionmentioning

confidence: 99%

Management of Adverse Events and Supportive Therapy in Relapsed/Refractory Multiple Myeloma

Pozzi

Bari

Pecherstorfer

et al. 2021

Cancers

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Relapsed/refractory (RR) multiple myeloma (MM) patients are a fragile population because of prolonged drug exposure and advanced age. Preserving a good quality of life is of high priority for these patients and the treatment of disease- and treatment-related complications plays a key role in their management. By preventing and limiting MM-induced complications, supportive care improves patients’ outcome. Erythropoietin-stimulating agents and bisphosphonates are well-established supportive strategies, yet novel agents are under investigation, such as anabolic bone agents and activin receptor-like kinase (ALK) inhibitors. The recent dramatic changes in the treatment landscape of MM pose an additional challenge for the routine care of RRMM patients. Multidrug combinations in first and later lines increase the risk for long-lasting toxicities, including adverse cardiovascular and neurological events. Moreover, recently approved first-in-class drugs have unique side-effect profiles, such as ocular toxicity of belantamab mafodotin or gastrointestinal toxicity of selinexor. This review discusses current standards in supportive treatment of RRMM patients, including recommendations in light of the recent SARS-CoV-19 pandemic, and critically looks at the incidence and management of side effects of standard as well as next generation anti-MM agents.

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“…At this dose level, the overall response rate was 65%. Grade 3-4 neutropenia was observed in 40% and Grade 1-2 CRS was observed in 70% of the patients ( 47 ). The second-generation CD3xBCMA BsAB AMG701 that has an Fc domain to extend its half-life ( 48 ) is being evaluated in an Phase 1/2 clinical study (NCT03287908).…”

Section: Clinical Impact Potential Of Bispecific T-cell Engagersmentioning

confidence: 99%

Dual Targeting of Multiple Myeloma Stem Cells and Myeloid-Derived Suppressor Cells for Treatment of Chemotherapy-Resistant Multiple Myeloma

Uckun

2021

Front. Oncol.

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Here we review the insights and lessons learned from early clinical trials of T-cell engaging bispecific antibodies (BsABs) as a new class of biotherapeutic drug candidates with clinical impact potential for the treatment of multiple myeloma (MM). BsABs are capable of redirecting host T-cell cytotoxicity in an MHC-independent manner to malignant MM clones as well as immunosuppressive myeloid-derived suppressor cells (MDSC). T-cell engaging BsAB targeting the BCMA antigen may help delay disease progression in MM by destroying the MM cells. T-cell engaging BsAB targeting the CD38 antigen may help delay disease progression in MM by depleting both the malignant MM clones and the MDSC in the bone marrow microenvironment (BMME). BsABs may facilitate the development of a new therapeutic paradigm for achieving improved survival in MM by altering the immunosuppressive BMME. T-cell engaging BsiABs targeting the CD123 antigen may help delay disease progression in MM by depleting the MDSC in the BMME and destroying the MM stem cells that also carry the CD123 antigen on their surface.

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Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study

Cited by 172 publications

References 19 publications

Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond

Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond

Management of Adverse Events and Supportive Therapy in Relapsed/Refractory Multiple Myeloma

Dual Targeting of Multiple Myeloma Stem Cells and Myeloid-Derived Suppressor Cells for Treatment of Chemotherapy-Resistant Multiple Myeloma

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