Marc S. Raab is a physician-scientist and Professor of Medicine at the Heidelberg University Medical Center (HUMC).

Dr Raab on Continued Investigation of Teclistamab Plus Daratumumab-Based Induction in Myeloma

"Phase 3 trials are planned or already underway for this newly diagnosed setting, [investigating] highly effective T-cell engagers in a setting where the T cells are treatment naive."

Marc S. Raab, MD, a professor of medicine and clinical director of the Heidelberg Myeloma Center in the Department of Medicine V at Heidelberg University Hospital, CCU Molecular Hematology/Oncology, German Cancer Research Center, discusses next steps for the investigation of teclistamab-cqyv (Tecvayli) in combination with daratumumab (Darzalex)–based induction regimens for the treatment of patients with newly diagnosed multiple myeloma based on results from the phase 2 MajesTEC-5 trial (NCT05695508).

During the 22nd Annual International Myeloma Society (IMS) Meeting and Exposition, findings from MajesTEC-5 showed that an overall response rate of 100% was achieved in all patients who received teclistamab every week in combination with daratumumab and lenalidomide (Revlimid; Tec-DR; n = 10), Tec-DR with teclistamab every 4 weeks ( n = 20) or teclistamab plus daratumumab, bortezomib (Velcade), and lenalidomide (n = 19). Beyond these high response rates, the depth of response was particularly notable. All patients with available samples had MRD negativity that was reached as early as after cycle 3, and was confirmed after cycle 6 using flow cytometry at a sensitivity of 10−5

Although MajesTEC-5 is a phase 2 study and does not yet change routine clinical practice, Raab stated that it opens a "clear avenue" for subsequent research. He added that phase 3 trials are currently being planned or are already underway in the newly diagnosed setting. The motivation for utilizing highly effective T-cell engagers in this initial stage of treatment is that the T cells are treatment naive, suggesting that therapy is likely most effective and most active in this stage, Raab concluded.

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Marc S. Raab, MD, discusses future avenues for the investigation of teclistamab plus daratumumab-based induction regimens in newly diagnosed multiple myeloma.

Dr Raab on Safety and Infection Prophylaxis With Daratumumab-Based Induction Regimens in Myeloma

"Infection prophylaxis is a key point if you combine a BCMA-targeting bispecific antibody with SOC drugs. Giving IVIG prophylactically... is key to keeping those rates as low as possible."

Marc S. Raab, MD, a professor of medicine and clinical director of the Heidelberg Myeloma Center in the Department of Medicine V at Heidelberg University Hospital, CCU Molecular Hematology/Oncology, German Cancer Research Center, shared safety data with teclistamab plus daratumumab (Darzalex) and lenalidomide (Revlimid) with or without bortezomib (Velcade) from the phase 2 MajesTEC-5 trial (NCT05695508), and emphasized the importance of infection prophylaxis when administering this regimen to patients with newly diagnosed multiple myeloma.

Findings shared during the 22nd Annual International Myeloma Society (IMS) Meeting and Exposition showed that all patients who received teclistamab every week in combination with daratumumab and lenalidomide (Tec-DR; arm A; n = 10), Tec-DR with teclistamab every 4 weeks (arm A1; n = 20) or teclistamab plus daratumumab, bortezomib, and lenalidomide (Tec-DVR; arm B; n = 19) achieved overall responses.

Although the overall safety profile was manageable across arms, Raab emphasized the crucial need to monitor infection rates when utilizing BCMA-directed bispecific antibodies, particularly in combination regimens. Of note, the initial rate of grade 3 or 4 infection presented at the 2024 ASH Annual Meeting was 34.7%. With longer follow-up, this rate slightly increased to 36.7%, indicating only one additional grade 3 or 4 infection was reported in one additional patient. Notably, no grade 5 infections occurred, and no patients were required to discontinue the study specifically due to infections.

However, due to the persistent risk of infection associated with this class of therapy, Raab stressed that infection prophylaxis is a crucial aspect of management when combining a BCMA-targeting bispecific antibody like teclistamab with SOC drugs. Key prophylactic measures required to minimize infection rates include administering IVIG prophylactically, along with prophylaxis against Pneumocystis pneumonia, anti-Zoster prophylaxis, and general antiviral prophylaxis, he concluded.

Marc S. Raab, MD, outlines the safety profile of teclistamab plus Dara-VRd in newly diagnosed multiple myeloma from the MajesTEC-5 trial.

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In today’s episode, we had the pleasure of speaking with Marc S. Raab, MD, about the post-induction outcomes and updated minimal residual disease (MRD) analyses from the phase 2 MajesTEC-5 study (NCT05695508), which is evaluating teclistamab-cqyv (Tecvayli)–based induction regimens in patients with newly diagnosed multiple myeloma. Dr Raab is a professor of medicine at Heidelberg University in Germany.

In our exclusive interview, Dr Raab discussed the rationale for integrating bispecific antibodies in the frontline multiple myeloma setting, the depth and durability of responses observed following teclistamab-based induction, and the implications of MRD findings for treatment sequencing and potential transplant strategies. He also highlighted key safety considerations, the role of step-up dosing, and how these data may shape evolving approaches to early T-cell–redirecting therapy in newly diagnosed disease.

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Marc S. Raab, MD, discusses evaluating teclistamab–based induction regimens in patients with newly diagnosed multiple myeloma

Teclistamab-Based Induction Is Effective and Generates MRD Negativity in Newly Diagnosed Myeloma: With Marc S. Raab, MD

Dr Raab on Patient Enrollment and the Design of the MajesTEC-5 Trial in NDMM

"This was a multicohort study where we tested different combinations and schedules... We also had a cohort where we added weekly bortezomib to resemble the Dara-VRd regimen from PERSEUS."

Marc S. Raab, MD, a professor of medicine and clinical director of the Heidelberg Myeloma Center in the Department of Medicine V at Heidelberg University Hospital, CCU Molecular Hematology/Oncology, German Cancer Research Center, provided an overview of the design and specific patient enrollment criteria for the phase 2 MajesTEC-5 trial (NCT05695508). This trial was designed to evaluate teclistamab-cqyv (Tecvayli) in combination with daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone with or without bortezomib (Velcade) for the treatment of patients with newly diagnosed multiple myeloma.

The patient population enrolled in the study was characteristic of a transplant-eligible group, with a median age of 58.0 years, indicating a relatively young cohort. The study enrolled patients with a substantial disease burden, as 44.9% of the patients were defined as having a high tumor load, indicated by a bone marrow infiltration rate of at least 60%. Furthermore, high-risk markers were identified in 20.4% of the enrolled patients.

MajesTEC-5 was structured as a multicohort study designed to test various combinations and dosing schedules. Several specific arms were created to investigate different approaches. In arm A, patients received teclistamab administered weekly in combination with lenalidomide and daratumumab, with dexamethasone limited only to the first 2 cycles. In arm A1, patients received the same combination regimen as Arm A, but the teclistamab dose was administered monthly instead of weekly. In arm B, patients received the monthly teclistamab schedule, to which weekly bortezomib was added. This specific regimen structure was intended to resemble the established Dara-VRd regimen seen in studies like the phase 3 PERSEUS trial (NCT03710603).

By utilizing this multicohort design, the trial sought to determine the optimal integration and scheduling of the bispecific antibody teclistamab within standard induction regimens for newly diagnosed multiple myeloma, Raab concluded

Marc S. Raab, MD, details the patient characteristics and design of the phase 2 MajesTEC-5 trial evaluating teclistamab in newly diagnosed multiple myeloma.

Dr Raab on the Rationale for Adding Teclistamab to Daratumumab-Based Induction in NDMM

"Although standard quadruplet induction regimens achieve high response rates, there remains room for improvement, as evidenced by the MRD negativity rate observed in studies like PERSEUS.”

Marc S. Raab, MD, a professor of medicine and clinical director of the Heidelberg Myeloma Center in the Department of Medicine V at Heidelberg University Hospital, CCU Molecular Hematology/Oncology, German Cancer Research Center, discussed the rationale for adding teclistamab-cqyv (Tecvayli) to standard daratumumab (Darzalex)–based induction regimens for the treatment of patients with newly diagnosed multiple myeloma.

The current standard-of-care (SOC) induction regimen for patients with newly diagnosed, transplant-eligible multiple myeloma is the quadruplet combination of daratumumab (Darzalex), bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Dara-VRd), Raab began. This regimen is known to achieve high response rates and long durations of response, he noted.

Despite the effectiveness of Dara-VRd, Raab noted that there remains "still room for improvement" in patient outcomes. As an example, the phase 3 PERSEUS study (NCT03710603), which evaluated Dara-VRd in this patient population, showed that the rate of minimal residual disease (MRD) negativity, even after transplant and consolidation, was 75.2%. This finding implies that nearly a quarter of patients still had detectable disease, prompting the search for more effective induction strategies, Raab explained.

The phase 2 MajesTEC-5 trial (NCT05695508) was designed to evaluate the safety and efficacy of enhancing the SOC by adding a bispecific antibody, specifically teclistamab-cqyv (Tecvayli), to regimens containing daratumumab, lenalidomide, dexamethasone and/or bortezomib in a phase 2 setting, he stated. By targeting BCMA with teclistamab early in the treatment pathway, researchers hoped to improve upon the high response rates achieved by Dara-VRd, Raab concluded.

Marc S. Raab, MD, discusses the rationale for assessing teclistamab plus daratumumab-based induction regimens in newly diagnosed multiple myeloma.

Dr Raab on Teclistamab-Based Regimens in Newly Diagnosed Multiple Myeloma 

“The response rates not only deepened over time but reached nearly 100% across all cohorts. The first cohort had a complete response [CR] rate of 100%, the second cohort had a CR rate of 95%, and the third [cohort] was a bit lower at 73.7%.”

Marc S. Raab, MD, a professor of medicine and the clinical director of the Heidelberg Myeloma Center in the Department of Medicine V at Heidelberg University Hospital discussed findings from a post-induction outcomes and minimal residual disease (MRD) analysis of the phase 2 MajesTEC-5trial (NCT05695508) of teclistamab-cqyv (Tecayli) for the treatment of patients with newly diagnosed multiple myeloma.

International Myeloma Society (IMS) Meeting and Exposition

, showed that patients who received teclistamab every week in combination with daratumumab and lenalidomide (Tec-DR; arm A; n = 10), Tec-DR with teclistamab every 4 weeks (arm A1; n = 20) or teclistamab plus daratumumab, bortezomib, and lenalidomide (Tec-DVR; arm B; n = 19) all achieved overall response rates of 100%, Raab began. Patients in arm A achieved a complete response (CR) or better rate of 100%, and those in arms A1 and B experienced CR or better rates of 95% and 73.7%, respectively, he added.

The MRD negativity rates across these arms were also promising, Raab noted. At a threshold of 10

, all patients in arms A (n = 10), A1 (n = 19), and B (n = 17) with available samples reached MRD negativity at the end of both cycle 3, he highlighted. These findings were confirmed at the end of cycle 6 by flow cytometry, he said. Overall, the cumulative MRD negativity rate across all arms (n = 49) by the end of induction in the efficacy analysis set was 98.0%.

Marc S. Raab, MD, discusses teclistamab for the treatment of patients with newly diagnosed multiple myeloma.

Raab IMS

“We found that the response rates not only deepened over time, but almost reached a 100% CR [rate] across all cohorts.”

Marc S. Raab, MD, PhD, a professor of medicine and clinical director of the Heidelberg Myeloma Center and the Department of Medicine V at the Heidelberg University Hospital, discussed updated findings from the phase 2 GMMG-HD10/DSMM-XX MajesTEC-5 (NCT05695508) study evaluating teclistamab-cqyv (Tecvayli)–based induction therapy in patients with newly diagnosed multiple myeloma.

22nd International Myeloma Society Annual Meeting

 included all 3 study cohorts, totaling 49 patients, all of whom completed 6 cycles of induction therapy. Across treatment arms, teclistamab/daratumumab (Darzalex)–based induction therapy produced deep and consistent responses, with an overall response rate (ORR) of 100% observed in all cohorts. In arm A (teclistamab weekly plus daratumumab; n = 10), all patients achieved a complete response (CR) or better. In arm A1 (teclistamab every 4 weeks plus daratumumab; n = 20), 95% of patients achieved a CR or better.

In arm B (teclistamab every 4 weeks plus daratumumab, bortezomib [Velcade], and lenalidomide [Revlimid]; n = 19), 73.7% of patients achieved a CR or better, 94.7% of patients achieved a very good partial response (VGPR) or better, and 5.3% of patients achieved a PR. Notably, several patients in arm B with a VGPR at the end of induction subsequently converted to a CR following autologous stem cell transplant. Collectively, all 49 patients responded to treatment by the end of induction.

Minimal residual disease (MRD) negativity was a key outcome of the study. Raab noted that MRD negativity by flow cytometry at a sensitivity of 10⁻⁵ was achieved in all MRD-evaluable patients, some as early as cycle 3, and MRD negativity was confirmed for all evaluable patients by cycle 6. Next-generation sequencing at a sensitivity of 10⁻⁶ confirmed MRD negativity in all 46 patients with available samples, yielding a 100% MRD-negative rate among tested patients and a 98.0% rate overall in the study population, Raab concluded.

Marc S. Raab, MD, PhD, discusses the efficacy of teclistamab-based induction in patients with newly diagnosed multiple myeloma.

Marc S. Raab, MD

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