The Use Talquetamab/Pomalidomide in Relapsed/Refractory Multiple Myeloma

Dr Matous on the Use Talquetamab/Pomalidomide in Relapsed/Refractory Multiple Myeloma

Jeffrey Matous, MD, member physician, Colorado Blood Cancer Institute, clinical professor of medicine, University of Colorado, discusses outcomes from the phase 1b MonumenTAL-2 trial (NCT05050097) with the combination of talquetamab-tgvs (Talvey) and pomalidomide (Pomalyst) in patients with relapsed/refractory multiple myeloma.

Results demonstrated that the median progression-free survival (PFS) was not reached in patients treated with 0.4 mg/kg of talquetamab plus pomalidomide every week (95% CI, 14.09- NR) as well as patients treated with 0.8 mg/kg of the study combination once every other week (95% CI, 7.43-NR). Additionally, talquetamab and pomalidomide demonstrated rapid, deep, and durable responses, with 93.8% of patients treated weekly and 84.2% of those treated biweekly experiencing benefit.

Importantly, there were no additional hematologic safety signals when talquetamab and pomalidomide were used in combination. Most of taste-, skin-, nail-, and rash-related adverse effects (AEs) were grade 1 or 2, with no instances of treatment discontinuation. A phase 3 trial investigating talquetamab and pomalidomide is planned for early 2024.

It is important to consider how combining a well-known agent with a novel therapeutic may impact toxicity, Matous begins. The hematologic AEs observed were consistent with the expected individual profiles of pomalidomide and talquetamab. These includedmanageable anemia and thrombocytopenia, he noted. Although cytokine release syndrome (CRS) was experienced by a majority of patients, it was mostly grade 1, and patients received tocilizumab for effective CRS management, Matous emphasizes.

Furthermore, infections—an established AE of concern for patients treated with BCMA-related bispecific antibodies—were relatively infrequent in this trial. This may be attributed to the absence of B-cell depletion with talquetamab and pomalidomide, he expands. This observation further substantiates the combination’s favorable safety profile. Overall, this research engenders future investigations of,and clinical applications for, talquetamab and pomalidomide, Matous concludes.

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Jeffrey Matous, MD, discusses outcomes from the phase 1b MonumenTAL-2 trial with the combination of talquetamab and pomalidomide in patients with relapsed/refractory multiple myeloma.


Jeffrey V. Matous, MD, clinical professor of medicine, University of Colorado Health Sciences Center, member physician, Colorado Blood Cancer Institute, discusses factors to be considered when determining the optimal sequencing of bispecific antibodies in multiple myeloma.

The selection and sequencing of currently available therapies with similar targets in multiple myeloma is dependent on several factors, including the availability of options at a given treatment center as well as patients’ unique circumstances, Matous says. Some academic centers, like the Colorado Blood Cancer Institute, offer a range of therapeutic options, including CAR T-cell therapy, clinical trials, and T cell–redirecting antibodies, he adds. However, community or rural practices may have a more limited array of options, according to Matous. As CAR T-cell therapy may not be feasible to integrate into community practice, bispecific antibodies may become a more promising option for patients in these locations, Matous adds.

Urgency also plays a critical role in treatment decision making. CAR T-cell therapy typically involves a waiting period of 5 weeks from cell collection to treatment. If immediate intervention is necessary for a patient, bispecific antibodies like teclistamab (Tecvayli) could represent a quicker alternative, Matous says.

Proximity to treatment centers is another consideration. Patients who live far away from the center might find weekly or biweekly visits for bispecific antibody treatment burdensome, whereas CAR T-cell therapy is administered through a single administration, Matous explains.

Regarding the sequencing of these drug classes, current data support the use of CAR T-cell therapy as initial treatment followed by bispecific antibodies in the event of disease recurrence. This sequential strategy allows for initial targeted treatment followed by a salvage option against the same or different targets, Matous states.

Ultimately, the choice of therapy is highly individualized and depends on a combination of these factors, ensuring that the selected treatment aligns with the patient’s specific needs, urgency, and circumstances, Matous concludes.

Jeffrey V. Matous, MD, discusses factors to be considered when determining the optimal sequencing of bispecific antibodies in multiple myeloma.
 

Dr Matous on Factors Influencing Treatment Selection and Sequencing in Multiple Myeloma

Jeffrey V. Matous, MD, member physician, Colorado Blood Cancer Institute, clinical professor of medicine, University of Colorado, discusses future directions of CAR T-cell therapy in multiple myeloma, highlighting the potential promise of novel targets beyond BCMA.

BCMA was a target that previously led to the development of several agents across the multiple myeloma treatment landscape, including bispecific antibodies and the CAR T-cell therapies idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti), which are both currently approved by the FDA, Matous begins. As more patients have been treated with BCMA-directed agents, there remains a question regarding subsequent treatments for this patient population following disease progression, Matous says.

Although switching from one BCMA-targeted agent to another following progression could be an option, he expands. it may also be a beneficial approach to target a different antigen on the surface of the malignant plasma cells, he says. This is where novel targets such as GPRC5D or FcRH5 come into play, Matous notes. Additionally, novel dual-targeting CAR T-cell therapies directed at CD19 and CD38 are also under development, Matous explains.

Having a variety of agents targeting different antigens is an attractive way to approach patients following disease progression, Matous continues. Additionally, Matous notes that clinicians at the University of Colorado Health Sciences Center have experience at their center treating patients with GPRC5D CAR T-cell therapy approaches after their disease did not responde well to a BCMA-targeted therapy. These approaches have generated excellent results thus far, making it a potential option for patients in this setting, Matous concludes.

Jeffrey V. Matous, MD, discusses future directions of CAR T-cell therapy in multiple myeloma, highlighting the potential promise of novel targets beyond BCMA.


Dr Matous on the Future Directions of CAR T-Cell Therapy in Multiple Myeloma

Jeffrey V. Matous, MD, member physician, Colorado Blood Cancer Institute, clinical professor of medicine, University of Colorado, discusses upcoming and ongoing clinical trials in multiple myeloma being conducted at Colorado Blood Cancer Institute. 

Cellular therapies remain a key area of interest in clinical trials for patients with multiple myeloma, Matous begins. Along with traditional CAR T-cell therapies, other cellular therapy approaches under investigation include natural killer cells, he notes. Furthermore, CAR T-cell therapies with novel targets beyond BCMA, such as GPRC5D and dual-targeting CAR T-cell therapies, are being evaluated, Matous says.

Continued investigations of BCMA-directed CAR T-cell therapies and bispecific antibodies are ongoing Colorado Blood Cancer Institute, including the phase 2 MajesTEC-1 trial (NCT04557098), which is evaluating teclistamab-cqyv (Tecvayli) in patients with relapsed/refractory multiple myeloma, Matous continues. The phase 1 TRIMM-3 trial (NCT05338775) is also investigating teclistamab or talquetamab in combination with a PD-1 inhibitor. Additionally, talquetamab is also being explored in various combinations in the phase 1 MonumenTAL-2 trial (NCT05050097). Studies of novel bispecific and trispecific antibodies are also planned, he adds.

One study of note that will soon open at Colorado Blood Cancer Institute is the ongoing phase 1/2 RedirecTT-1 trial (NCT04586426), which is evaluating the combination talquetamab and teclistamab in patients with relapsed/refractory multiple myeloma who have extramedullary disease. This study aims to address an area of major unmet need, Matous concludes.

Jeffrey V. Matous, MD, discusses upcoming and ongoing clinical trials in multiple myeloma being conducted at the Colorado Blood Cancer Institute.


Dr Matous on Ongoing Multiple Myeloma Clinical Trials at Colorado Blood Cancer Institute

Jeffrey V. Matous, MD, member physician, Colorado Blood Cancer Institute, clinical professor of medicine, University of Colorado, 

discusses the benefit derived from the phase 3 IKEMA trial (NCT03275285) in patients with relapsed/refractory multiple myeloma

, highlighting the key factors to take into account when evaluating patients for relapsed/refractory disease within this treatment space.

The phase 3 trial evaluated the combination of isatuximab-irfc (Sarclisa), carfilzomib (Kyprolis), and dexamethasone, showing a 42% reduction in the risk of progression or death vs treatment with carfilzomib plus dexamethasone alone (HR, 0.58; 95.4% CI, 0.42-0.79). The median progression-free survival (PFS) was 35.7 months (95% CI, 25.8-44.0) for the triplet vs 19.2 months (95% CI, 15.8-25.0) for the doublet.

The isatuximab, carfilzomib, and dexamethasone triplet regimen is a potent approach in this treatment space, Matous says. There were significant PFS advantages derived in patients who received the triplet, representing an improvement over the doublet and other, older, standard-of-care regimens, Matous explains. Notably, this is a well-tolerated regimen which produced high and durable response rates in this patient population, he adds. He notes that this triplet is a beneficial regimen to consider for patients in this space, specifically if patients have not yet received carfilzomib or a recent CD-38 antibody.

Moreover, given the variety of options now available for patients with multiple myeloma, there are many factors to take into account when evaluating different approaches to take for patients with relapsed/refractory disease, Matous continues. When evaluating a patient with relapsed/refractory multiple myeloma, it is important to consider comorbidities, prior therapy, response to prior therapy, and the type of relapse, Matous says.

A history of neuropathy and financial concerns can also play a role in treatment decisions for patients, Matous adds. Processing all these factors and having discussions with patients are key to deciding on treatment beyond the first line of therapy, Matous concludes.

Jeffrey V. Matous, MD, discusses the benefit derived from the phase 3 IKEMA trial in patients with relapsed/refractory multiple myeloma, highlighting the key factors to take into account when evaluating patients for relapsed/refractory disease within this treatment space.


Dr Matous on the Benefit Derived from the IKEMA Trial in R/R Multiple Myeloma

Jeffrey V. Matous, MD, member physician, Colorado Blood Cancer Institute, clinical professor of medicine, University of Colorado, discusses potential strategies to overcome barriers to receiving CAR T-cell therapy for patients with multiple myeloma, and how the potential use of these agents in earlier lines could improve infusion wait times and rates of disease progression.

Most patients receiving CAR T-cell therapy will need to wait approximately 5 weeks from the time of apheresis until the infusion of their autologous CAR T cells, Matous begins. During that time, some patients will exhibit aggressive disease that requires bridging therapy to prevent progression, he says. In a clinical trial setting, some of these patients have had to discontinue participation in the study, preventing them from receiving CAR T-cell therapy due to progressive disease, Matous adds.

Accordingly, efforts to decrease the manufacturing time needed for autologous CAR T cells or produce an effective off-the-shelf CAR T-cell therapy remain substantial interests in the field, Matous states, noting that several research groups are pursuing these strategies.

Meanwhile, investigations of both idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti), in earlier lines of therapy could also improve disease control for some patients, Matous continues. Administration of these CAR T-cell therapies in the second or third line could improve patients’ T-cell repertoire, as well as their ability to tolerate these treatments, he explains.

Long-term findings for cilta-cel from the phase 1/2 CARTITUDE-1 trial (NCT03548207) alongside recently presented findings from the phase 3 CARTITUDE-4 trial (NCT04181827) corroborate this prediction, Matous says.

Notably, data from CARTITUDE-4 showed a progression-free survival (PFS) advantage with cilta-cel vs standard-of-care (SOC) pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd) in pretreated patients with lenalidomide (Revlimid)-refractory multiple myeloma. This PFS benefit indicated that earlier administration of CAR T-cell therapies such as cilta-cel could improve both outcomes and tolerability with this drug class, Matous concludes.

Jeffrey V. Matous, MD, discusses potential strategies to overcome barriers to receiving CAR T-cell therapy for patients with multiple myeloma, and how the potential use of these agents in earlier lines could improve infusion wait times and rates of disease progression.

Jeffrey V. Matous, MD

Articles

Dr Matous on the Use Talquetamab/Pomalidomide in Relapsed/Refractory Multiple Myeloma

Dr Matous on Factors Influencing Treatment Selection and Sequencing in Multiple Myeloma

Dr Matous on the Future Directions of CAR T-Cell Therapy in Multiple Myeloma

Dr Matous on Ongoing Multiple Myeloma Clinical Trials at Colorado Blood Cancer Institute

Dr Matous on the Benefit Derived from the IKEMA Trial in R/R Multiple Myeloma

Dr Matous on Barriers to CAR T-Cell Therapy Administration in Multiple Myeloma