Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Phase 1/2 Results from MonumenTAL-1

Chari, Ajai; Touzeau, Cyrille; Schinke, Carolina; Minnema, Monique C.; Berdeja, Jesús G.; Oriol, Albert; Donk, N. W. van de; Otero, Paula Rodríguez; Askari, Elham; Mateos, María‐Victoria; Costa, Luciano J.; Caers, Jo; Rasche, Leo; Krishnan, Amrita; Vishwamitra, Deeksha; Ma, Xuewen; Qin, Xiang; Gries, Katharine S.; Campagna, Michela; Masterson, Tara; Tolbert, Jaszianne; Renaud, Thomas; Goldberg, Jenna D.; Heuck, Christoph; San-Miguel, Jesús F.; Moreau, Philippe

doi:10.1182/blood-2022-159707

Cited by 33 publications

(63 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, several studies showed that the R/R MM patients who had experienced relapse after anti-BCMA CAR-T cell therapy could also benefit from carfilzomib-based therapy, venetoclax-based therapy, and selinexor-based therapy (132)(133)(134)136). In addition, T cell redirecting bispecific antibodies, such as Cevostamab and Talquetamab, have also proved to be feasible salvage treatment after anti-BCMA CAR-T cell therapy and able to induce durable responses (137)(138)(139). Moreover, a phospholipid-drug complex Iopofosine I-131 could also achieve clinical responses in R/R MM patients who had failed in prior anti-BCMA therapy (140).…”

Section: Subsequent Anti-myeloma Therapy After Car-t Therapymentioning

confidence: 99%

CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies

Zhang

Zhang²,

Lan³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

Over the last decade, the survival outcome of patients with multiple myeloma (MM) has been substantially improved with the emergence of novel therapeutic agents, such as proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies, selective inhibitors of nuclear export (SINEs), and T cell redirecting bispecific antibodies. However, MM remains an incurable neoplastic plasma cell disorder, and almost all MM patients inevitably relapse due to drug resistance. Encouragingly, B cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (CAR-T) cell therapy has achieved impressive success in the treatment of relapsed/refractory (R/R) MM and brought new hopes for R/R MM patients in recent years. Due to antigen escape, the poor persistence of CAR-T cells, and the complicated tumor microenvironment, a significant population of MM patients still experience relapse after anti-BCMA CAR-T cell therapy. Additionally, the high manufacturing costs and time-consuming manufacturing processes caused by the personalized manufacturing procedures also limit the broad clinical application of CAR-T cell therapy. Therefore, in this review, we discuss current limitations of CAR-T cell therapy in MM, such as the resistance to CAR-T cell therapy and the limited accessibility of CAR-T cell therapy, and summarize some optimization strategies to overcome these challenges, including optimizing CAR structure, such as utilizing dual-targeted/multi-targeted CAR-T cells and armored CAR-T cells, optimizing manufacturing processes, combing CAR-T cell therapy with existing or emerging therapeutic approaches, and performing subsequent anti-myeloma therapy after CAR-T cell therapy as salvage therapy or maintenance/consolidation therapy.

show abstract

Section: Subsequent Anti-myeloma Therapy After Car-t Therapymentioning

confidence: 99%

CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies

Zhang

Zhang²,

Lan³

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…The phase I MonumenTAL-1 trial assessed talquetamab monotherapy in 232 heavily pretreated patients (median of 6 prior lines of therapies); 79% had triple-class-refractory disease, 30% penta-drug-refractory disease and 87% disease refractory to the last line of therapy. After a median follow up of 11.7 months (for patients who received the 405-μg dose level) and 4.2 months (for patients who received the 800-μg dose level), ORR was 70% and 64%, respectively, with median duration of response being 10.2 months and 7.8 months, respectively [ 160 , 161 , 162 ].…”

Section: Available Therapeutic Modalitiesmentioning

confidence: 99%

Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

Dima

Ullah

Mazzoni

et al. 2023

Cancers

View full text Add to dashboard Cite

Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases. Patients eventually relapse and become refractory to multiple drug classes, making long-term management challenging. In this review, we will focus on the treatment paradigm of relapsed/refractory MM (RRMM) in the era of advanced therapies emphasizing the available novel modalities that have recently been incorporated into routine practice, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and other promising approaches. We will also discuss major factors that influence the selection of appropriate drug combinations or cellular therapies, such as relapse characteristics, and other disease and patient related parameters. Our goal is to provide insight into the currently available and experimental therapies for RRMM in an effort to guide the therapeutic decision-making process.

show abstract

“…Talquetamab (JNJ-64407564) demonstrated in preclinical studies to induce T cell activation and degranulation, MM cells lysis, IFN-g, TNF-a, IL-2 and IL-10 cytokines activation [ 194 , 195 ]. Talquetamab showed a 73% ORR in 143 RRMM patients with median of 5 prior LOT) enrolled in the phase I/II MonumenTAL-1 trial [ 196 , 197 ], with comparable ORR between triple-refractory or penta-refractory and the ITT population. Median DOR was 9.3 months and median PFS 7.5 months.…”

Section: Sequential Therapy In Relapsed/refractory MM In Light Of New...mentioning

confidence: 99%

“…As for safety, grade ≥ 3 CRS was reported in less than 3% of patients and grade ≥ 3 infections in about 17%. The novel toxicities of this drug were skin-related, nail disorders and dysgeusia occurring in 56%, 52% and 48% of patients, respectively [ 196 , 197 ]. These clinical benefits were confirmed by patient-reported outcomes which endorsed the improvement of quality of life [ 198 ].…”

Section: Sequential Therapy In Relapsed/refractory MM In Light Of New...mentioning

confidence: 99%

Current Main Topics in Multiple Myeloma

Morè¹,

Corvatta²,

Manieri³

et al. 2023

Cancers

View full text Add to dashboard Cite

Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance therapy, has led to a significant improvement of PFS and OS.; however, this outcome remains poor in ultra-high risk MM or in those who did not achieve a minimal residual disease (MRD) negativity. Several trials are exploring cytogenetic risk-adapted and MRD-driven therapies in these patients. Similarly, quadruplets-containing daratumumab, particularly when administered as continuous therapies, have improved outcome of patients not eligible for autologous transplant (NTE). Patients who become refractory to conventional therapies have noticeably poor outcomes, making their treatment a difficult challenge in need of novel strategies. In this review, we will focus on the main points regarding risk stratification, treatment and monitoring of MM, highlighting the most recent evidence that could modify the management of this still incurable disease.

show abstract

Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Phase 1/2 Results from MonumenTAL-1

Cited by 33 publications

References 0 publications

CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies

CAR-T cell therapy in multiple myeloma: Current limitations and potential strategies

Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

Current Main Topics in Multiple Myeloma

Contact Info

Product

Resources

About