Dr Grajales-Cruz on Real-World Teclistamab Data in BCMA-Pretreated Multiple Myeloma

Ariel Grajales-Cruz, MD, assistant member, Department of Malignant Hematology, Multiple Myeloma Section, Moffitt Cancer Center; assistant professor, University of South Florida, discusses the rationale for 

a real-world study of teclistamab-cqyv (Tecvayli)

 in patients with relapsed/refractory multiple myeloma who had received prior BCMA-directed therapy.

Bispecific antibodies are an evolving treatment option for patients with relapsed/refractory multiple myeloma, Grajales-Cruz says. Historically, after patients progressed on standard therapies, they did not have many treatment options, Grajales-Cruz notes. However, 3 bispecific antibodies are now approved by the FDA for patients with relapsed/refractory multiple myeloma. Teclistamab, a dual BCMA- and CD3-directed agent, 

 for patients with relapsed/refractory disease who have received 4 or more prior lines of therapy, including a proteasome inhibitor (PI) an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody. In August 2023, the FDA approved both 

Findings from the single-arm, phase 2 MajesTEC-1 trial (NCT04557098), which investigated teclistamab in patients with relapsed/refractory multiple myeloma, supported the FDA approval of teclistamab. In this trial, teclistamab elicited an overall response rate of 61.8% (95% CI, 52.1%-70.9%) in patients with multiple myeloma who were relapsed/refractory to 3 or more prior therapies, including a PI, an IMiD, and an anti-CD38 monoclonal antibody (n = 110). Furthermore, at a median follow-up of 7.4 months, the estimated 9-month duration of response rate among responders was 66.5% (95% CI, 38.8%-83.9%).

However, the patient population in MajesTEC-1 did not include those with prior exposure to other BCMA-directed therapies, thus limiting oncologists’ ability to translate the data from MajesTEC-1 to the real-world setting, Grajales-Cruz explains. Variations in patient characteristics often exist between clinical trial populations and real-world populations, particularly in the community setting, Grajales-Cruz emphasizes. These population discrepancies prompted the evaluation of teclistamab in a real-world relapsed/refractory multiple myeloma population in comparison with the MajesTEC-1 population, Grajales-Cruz concluded.

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Ariel Grajales-Cruz, MD, discusses the rationale for a real-world study of teclistamab in patients with myeloma who had received BCMA-directed therapy.

Dr Grajales-Cruz on Future Research Directions With Teclistamab in R/R Multiple Myeloma

Ariel Grajales-Cruz, MD, assistant member, Department of Malignant Hematology, Multiple Myeloma Section, Moffitt Cancer Center, discusses next steps for research elucidating the role of teclistamab (Tecvayli) monotherapy for patients with relapsed/refractory multiple myeloma.

, findings were presented from a retrospective, single-center study of the real-world efficacy of teclistamab in heavily pretreated patients with multiple myeloma who had progressed on a prior BCMA-directed therapy. The overall response rate (ORR) with teclistamab in the real-world setting was 52.8%, with a complete response rate of 44.5%. Furthermore, the median progression-free survival (PFS) was 8 months. These ORR and PFS rates were comparable with those observed in patients without prior BCMA therapy exposure from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098). In this pivotal trial, the ORR with teclistamab was 63%, and the median PFS was 11.3 months.

Although these data affirm the efficacy of teclistamab across both clinical and real-world multiple myeloma settings, several unanswered questions remain regarding the optimal use of teclistamab in relapsed/refractory multiple myeloma, Grajales-Cruz begins. The current body of evidence in myeloma indicates that responses to CAR T-cell therapy are not always similar in patients who have received prior BCMA-directed therapy compared with those who have not, Grajales-Cruz explains. However, teclistamab has demonstrated benefit in populations of patients with multiple myeloma with prior exposure to BCMA-directed therapy, he notes.

Research efforts in multiple myeloma should therefore focus on elucidating the optimal sequencing of teclistamab with other novel agents, such as CAR T-cell therapies, elranatamab-bcmm (Elrexfio), and talquetamab (Talvey), Grajales-Cruz states, adding that investigations should place particular emphasis on patients who have received prior BCMA-directed therapy. Understanding how prior exposure to BCMA-directed therapy impacts responses to subsequent treatments and vice versa is essential for informing clinical decision-making and improving survival outcomes, Grajales-Cruz concludes.

Ariel Grajales-Cruz, MD, discusses research elucidating the role of teclistamab monotherapy for patients with relapsed/refractory multiple myeloma.

Dr Grajales-Cruz on the Safety of Teclistamab in Multiple Myeloma

Ariel F. Grajales-Cruz, MD, assistant member, Myeloma Section, Department of Malignant Hematology, Moffitt Cancer Center, discusses a retrospective analysis on real-world efficacy with teclistamab-cqyv (Tecvayli) in patients with relapsed/refractory multiple myeloma following BCMA-directed therapy. 

, no new safety concerns emerged, Grajales-Cruz begins. As anticipated, some patients experienced cytokine release syndrome (CRS), although no instances of CRS exceeded grade 2 severity, and no instances of grade 3 or 4 CRS were observed. The incidence of CRS was lower in the real-world population compared with that in the clinical trial population, which was promising, according to Grajales-Cruz. Similar observations were noted regarding neurotoxicity rates, with fewer occurrences reported in the real-world analysis than in the pivotal MajesTEC-1 trial (NCT04557098). The observed toxicities in the real-world population were largely within expected parameters, he elucidates.

Infections remain a significant concern, particularly given the hypogammaglobulinemic state of these patients, he says. The consideration of intravenous immunoglobulin, prophylactic medications, and antivirals, especially in patients receiving teclistamab, is crucial, particularly for those with a CD4 count below 200 cells/mm3. Such patients are at increased risk of opportunistic infections, necessitating the consideration of prophylactic measures, such as pentamidine, to mitigate the risk of pneumonia, Grajales-Cruz explains. 

A key unanswered question pertains to treatment sequencing. The optimal sequence of therapies for patients with relapsed/refractory multiple myeloma remains elusive, particularly considering the variable responses observed in patients who have received prior BCMA-directed therapy, Grajales-Cruz expands. Although responses to CAR T-cell therapy may differ in such cases, the reverse sequence appears less impactful, he notes.

Despite this, encouraging results and responses have been noted with teclistamab in patient populations previously treated with BCMA-directed therapy, Grajales-Cruz continues. However, with the emergence of additional therapies, such aselranatamab-bcmm (Elrexfio) and talquetamab-tgvs (Talvey), the sequencing of these treatments becomes paramount. Determining the optimal sequence will be essential for achieving prolonged progression-free survival and overall survival in this patient population, he states. Although myeloma remains incurable, the expanding array of treatment options underscores its increasing manageability. Addressing the sequencing of therapies will be a pivotal focus in the coming years, Grajales-Cruz concludes.

Ariel F. Grajales-Cruz, MD, discusses the real-world efficacy of teclistamab in relapsed/refractory multiple myeloma. 

Dr Grajales-Cruz on Benefit With Teclistamab in Select Patients With Relapsed/Refractory Myeloma

Ariel Grajales-Cruz, MD, assistant member, Department of Malignant Hematology, Multiple Myeloma Section, Moffitt Cancer Center, discusses disease factors and patient characteristics associated with benefit from teclistamab (Tecvayli) monotherapy in patients with relapsed/refractory multiple myeloma, according to findings from a real-world analysis of heavily pretreated patients with relapsed/refractory multiple myeloma who progressed on a prior BCMA-directed therapy.

The retrospective, single-center study evaluated the real-world efficacy of teclistamab, a standard-of-care therapy for heavily pretreated patients with multiple myeloma. The study compared the results from this real-world setting to those observed in the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098).

, results showed that real-world teclistamab produced an overall response rate of 63%, including a complete response rate of 36%. These response rates were comparable with those observed in patients from the MajesTEC-1 trial who were not previously exposed to BCMA therapy, highlighting the consistency of teclistamab's efficacy across different patient populations. No new safety signals were observed.

One of the key questions addressed by the study was whether any specific subgroups of patients experienced better outcomes with teclistamab, Grajales-Cruz begins. Interestingly, the study found that responses were not dependent on the type of regimens previously received, he says. This included prior treatment with BCMA-targeted therapy, including CAR T-cell therapy, antibody-drug conjugates, or other bispecific antibodies. Additionally, high-risk disease status was not found to be a predictor of response, Grajales-Cruz states. However, patients with a poorer ECOG performance status (PS) of 2 or more experienced worse outcomes and achieved a shorter median progression-free survival vs patients with an ECOG PS of 0 or 1, Grajales-Cruz explains.

Overall, findings support the consistent efficacy of teclistamab across different patient populations and indicate that ECOG PS should be considered when assessing potential treatment outcomes with teclistamab in this setting, Grajales-Cruz concludes.

Ariel Grajales-Cruz, MD, discusses factors associated with benefit from teclistamab in heavily pretreated relapsed/refractory multiple myeloma.

Dr Grajales-Cruz on Real-World Responses With Teclistamab in Pretreated R/R Multiple Myeloma

Ariel Grajales-Cruz, MD, assistant Member, Department of Malignant Hematology, Multiple Myeloma Section, Moffitt Cancer Center, discusses real-world safety and efficacy outcomes from treatment with the bispecific antibody teclistamab (Tecvayli) in heavily pretreated patients with relapsed/refractory multiple myeloma who progressed on aprior BCMA-directed therapy.

A retrospective, single-center study assessed the real-world efficacy of this standard-of-care therapy relative to results from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098), Ariel Grajales-Cruz, MD begins. In this trial, teclistamab produced an objective response rate of 63%, he reports, and a median progression-free survival (PFS) of 11.3 months. Such findings supported 

the FDA approval of teclistamab in October 2022

 in the treatment of patients with relapsed/refractory multiple myeloma who had received at least 4 previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

demonstrated a favorable overall response rate of 63% with teclistamab in heavily pretreated patients in clinic, with a complete response rate of 36%, Grajales-Cruz states. These response rates were comparable to that of patients in the MajesTEC-1 trial, who were not previously exposed to prior BCMA therapy, he emphasizes. No new safety signals were identified.

Unlike the MajesTEC-1 trial, this real-world cohort comprised of more heavily pretreated patients, Grajales-Cruz reports, adding that 36 individuals had been treated with BCMA-directed therapies, including CAR T-cell therapy, antibody-drug conjugates, or other bispecific antibodies. The study also enrolled approximately 45% of patients with high-risk features as well as frailer patients with an ECOG performance status of 2 or greater, Grajales-Cruz states. Despite including a more difficult-to-treat patient population, the study demonstrated results with teclistamab that align closely with outcomes observed in the original MajesTEC-1 trial, Grajales-Cruz says. This underscores the robustness and effectiveness of teclistamab across diverse patient profiles, he concludes.

Ariel Grajales-Cruz, MD, discusses real-world safety and efficacy outcomes with teclistamab in select patients with relapsed/refractory multiple myeloma.

Ariel Grajales-Cruz, MD

Articles

Dr Grajales-Cruz on Real-World Teclistamab Data in BCMA-Pretreated Multiple Myeloma

Dr Grajales-Cruz on Future Research Directions With Teclistamab in R/R Multiple Myeloma

Dr Grajales-Cruz on the Safety of Teclistamab in Multiple Myeloma

Dr Grajales-Cruz on Benefit With Teclistamab in Select Patients With Relapsed/Refractory Myeloma

Dr Grajales-Cruz on Real-World Responses With Teclistamab in Pretreated R/R Multiple Myeloma