Dr Dima on Real-World Responses With Teclistamab in R/R Multiple Myeloma

Danai Dima, MD, hematology-oncology fellow, Cleveland Clinic, discusses the outcomes of a real-world analysis with teclistamab-cqyv (Tecvayli) compared with outcomes that have previously been observed in a clinical trial setting for patients with pretreated, relapsed/refractory multiple myeloma.

 of patients with pretreated, relapsed/refractory multiple myeloma showed that the agent was effective and tolerable, Dima begins. The overall response rate (ORR) with teclistamab in clinical practice was 66%, including a complete response (CR) or better in 29% of patients. These outcomes align closely with results from the phase 2 MajesTEC-1 trial (NCT04557098), which had stricter eligibility criteria and excluded patients with high-risk disease features, Dima explains. In the MajesTEC trial, the ORR for patients without prior BCMA therapy exposure was also 63%, with a CR of 39.4%, she adds.

 for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 4 previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, Dima states. This regulatory approval addresses an unmet need in this patient population that has historically had limited treatment options, she says. Unlike CAR T-cell therapies, which require a prolonged manufacturing time and may not be suitable for patients with more severe disease, teclistamab offers a readily available therapeutic option with comparable efficacy in terms of response rates and PFS, Dima explains.

The findings underscore the potential of teclistamab as an effective and more accessible treatment option for patients with relapsed/refractory multiple myeloma who have exhausted standard treatment regimens, Dima emphasizes. This real-world evidence reinforces the results from clinical trials and supports the integration of teclistamab into the treatment landscape for heavily pretreated multiple myeloma patients, she concludes.

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Danai Dima, MD, discusses real-world responses with teclistamab in relapsed/refractory multiple myeloma.

Dr Dima on the Mechanism of Action of Teclistamab in Relapsed/Refractory Multiple Myeloma

Danai Dima, MD, hematology-oncology fellow, Cleveland Clinic, discusses the mechanism of action of teclistamab-cqyv (Tecvayli) in pretreated patients with relapsed/refractory multiple myeloma, as well as the rationale for investigating the efficacy and safety of this agent a real-world patient cohort.

Teclistamab is a bispecific antibody that targets BCMA, which is expressed on the surface of plasma cells, and CD3, which is expressed on the surface of T cells, Dima begins. By binding to both BCMA and CD3, teclistamab forms an immunologic bridge that activates T cells, leading to the destruction of malignant plasma cells, she explains.

teclistamab was approved by the FDA for the treatment of patients with relapsed/refractory multiple myeloma

 who have received at least 4 previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, Dima adds.

This regulatory decision was based on the results of the pivotal phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098), she continues. In the single-arm, open-label, multicenter trial, teclistamab demonstrated an overall response rate of 63.0% (95% CI, 55.2%-70.4%), including a very good partial response or better in 58.8% of patients, and a complete response or better in 39.4% of patients. The agent also produced a median progression-free survival of 11.3 months (95% CI, 8.8-17.1).

Although the MajesTEC-1 trial supported the approval of teclistamab, its stringent eligibility criteria excluded many patients with high-risk features, Dima notes. This included patients with significant organ dysfunction, significant comorbidities, severe cytopenias, high-risk disease characteristics, and prior BCMA-directed therapy exposure, she says. Accordingly, the trial may not have fully represented patients being treated with the agent in clinical practice, according to Dima. To account for this potential discrepancy, a real-world, retrospective study of outcomes with teclistamab in pretreated patients with relapsed/refractory multiple myeloma was conducted, Dima explains.

Findings from the real-world study, presented at 

, showed that the administration of the T-cell redirecting bispecific antibody was effective and well tolerated in a heavily pretreated patient population, most of whom did not meet the eligibility criteria for the MajesTEC-1 trial and had high-risk disease features. Moreover, the real-world rates of BCMA-related adverse effects are comparable with those in the MajesTEC-1 trial, although the occurrence of severe cytokine release syndrome and neurotoxicity in this patient population was relatively low in comparison, Dima concludes.

Danai Dima, MD, discusses the mechanism of action of teclistamab and why real-world outcomes with the agent were evaluated in a retrospective study.

Dr Dima on the Implications of a Real-World Analysis of Teclistamab in Multiple Myeloma

Danai Dima, MD, hematology-oncology fellow, Cleveland Clinic, discusses the implications of real-world data derived from the phase 2 MajesTEC-1 trial (NCT04557098), an investigation of treatment with teclistamab-cqyv (Tecvayli) in pretreated patients with relapsed/refractory multiple myeloma, findings from which were presented at 

Administration of the T-cell redirecting bispecific antibody teclistamab 

showed effectiveness and a well-tolerated safety profile in this real-world cohort of patients

, mirroring the outcomes observed in patients enrolled onto the MajesTEC-1 trial, Dima begins. This real-world analysis, which incorporated multivariate analyses, revealed that patients who had undergone more than 4 lines of therapy exhibited lower response rates, she says. This underscores the importance of early utilization of teclistamab for optimal effectiveness. Many oncologists, whether in academic centers or community practices, may hesitate to employ novel agents in patients with significant illnesses, baseline comorbidities, and organ dysfunction, Dima explains. However, these findings provide evidence that teclistamab is well tolerated and effective even in very ill patients, offering encouraging insights that can prove valuable for oncologists, she emphasizes.

Adverse events (AEs) associated with BCMA-directed bispecific antibodies primarily include cytokine release syndrome (CRS) and neurotoxicity, Dima continues. The real-world rates of these AEs observed in the analysis align with those in the MajesTEC-1 trial, but notably, the occurrence of severe CRS and neurotoxicity, defined as that of grade 3 or higher, in this patient population was relatively low, she elucidates. This raises the possibility of administering teclistamab via step-up dosing in an outpatient setting without hospitalization, provided appropriate infrastructure and resources are in place, Dima states.

Moreover, these findings indicate that community oncologists can potentially manage treatment with teclistamab after the initial step-up dosing, Dima expands. However, it's crucial to acknowledge the high infection and cytopenia risk in these patients, emphasizing the need for vigilant monitoring and close follow up by community oncologists, she says. Ensuring patients receive necessary supportive care, including intravenous immune globulin, growth factors, antimicrobials, and vaccinations, is essential to mitigate the risk of non-relapse mortality, Dima emphasizes.

Although this real-world study had a short follow up, necessitating longer observation for response deepening and durability, the data provide reassurance, especially for community oncologists, that teclistamab is associated with a favorable safety profile, particularly in severely ill patients, Dima notes. The low rates of severe CRS and neurotoxicity, coupled with proper supportive care, can contribute to avoiding AEs such as infections and preventing non-relapse mortality, she concludes.

Danai Dima, MD, discusses the implications of real-world data derived from the MajesTEC-1 trial in pretreated patients with multiple myeloma.

Danai Dima, MD

Articles

Dr Dima on Real-World Responses With Teclistamab in R/R Multiple Myeloma

Dr Dima on the Mechanism of Action of Teclistamab in Relapsed/Refractory Multiple Myeloma

Dr Dima on the Implications of a Real-World Analysis of Teclistamab in Multiple Myeloma