Emerging BsAbs and Their Impact in Multiple Myeloma

ONGOING RESEARCH evaluating bispecific antibody (BsAb) therapy is generating excitement, particularly in multiple myeloma, due to the potential use in earlier lines of therapy and in the maintenance setting. Although the data are not expected to mature for the next few years, BsAbs are beginning to completely transform the treatment landscape as approvals expand to more cancer types.

Part 2 of this 3-part series will focus on what investigators are currently evaluating and its potential impact.

“Bispecific antibody therapies are not limited to myeloma, but [they] are currently approved for lymphomas, leukemias, small cell lung cancer and melanoma, and there are more BsAbs in the pipeline for other disease indications as well. The community has to learn how to use them, otherwise it is not sustainable for only academic centers to offer these, and it is not amenable for the patients as well,” Ajay K. Nooka, MD, MPH, told Targeted Therapies in Oncology in an interview. Nooka is director of myeloma program and associate director of clinical research for Winship Cancer Institute of Emory University in Atlanta, Georgia.

Currently, the 3 BsAbs approved, with accelerated approvals, for relapsed/refractory multiple myeloma are teclistamab (Tecvayli; approved in October 2022), elranatamab (Elrexfio; approved in August 2023), and talquetamab (Talvey, approved in August 2023).¹ To gain full approval, the randomized phase 3 studies comparing these agents with the standard of care (SOC) need to be completed. Some of these ongoing studies include the MajesTEC-3 (NCT05083169), MajesTEC-4 (NCT05243797) and MajesTEC-7 (NCT05552222) trials for teclistamab; MagnetisMM-5 (NCT05020236) and MagnetisMM-7 (NCT05317416) for elranatamab; and MonumenTAL-5 (NCT05461209) and MonumenTAL-6 (NCT06208150) for talquetamab.

These trials are underway for early- relapse and maintenance settings, and they “will change how we treat myeloma,” Nooka said. For instance, both the early relapse and maintenance trials are designed to show superior progression-free survival for all patients, and they may show this potential benefit vs SOC therapies. In this context, the emphasis is on a benefit for all patients, and thus broad community participation would be essential, Nooka said.

On the Horizon

The phase 3 MajesTEC-7 study is evaluating patients with newly diagnosed multiple myeloma who are either ineligible or cannot receive an autologous stem cell transplant as initial therapy.² Researchers will investigate teclistamab in combination with subcutaneous (SC) daratumumab (Darzalex) and lenalidomide (Revlimid) as well as talquetamab in combination with SC daratumumab and lenalidomide against SC daratumumab, lenalidomide, and dexamethasone in the frontline setting.

In addition, the randomized, open- label, multicenter, phase 3 MajesTEC-4 trial is an ongoing trial evaluating teclistamab plus lenalidomide against lenalidomide alone as maintenance therapy.³ This treatment follows autologous stem cell transplantation and involves patients with newly diagnosed multiple myeloma. According to investigators, “It is anticipated that the combination of teclistamab plus lenalidomide in the maintenance setting will provide greater efficacy than lenalidomide alone.”

The phase 3 MagnetisMM-5 trial is evaluating elranatamab alone; elranatamab with daratumumab; or daratumumab, pomalidomide, and dexamethasone.4 In contrast, this 2-part trial involves patients with multiple myeloma who have received at least 1 prior line of therapy. Part 1 will assess the safety and activity of different doses of elranatamab in combination with daratumumab. Part 2 will compare the safety and activity of elranatamab alone vs daratumumab, pomalidomide, and dexamethasone; and elranatamab plus daratumumab vs daratumumab, pomalidomide, and dexamethasone, according to investigators.

BsAbs are specifically meant for the community [setting], Nooka noted. “Ultimately, the goal should be for patients to receive these drugs close to home.” It is only a matter of time before clinicians will need to learn how to administer BsAbs due to their growing use across cancer types and “once we receive the indication to administer [BsAbs in] early lines of therapy, it will be a game changer,” Nooka said. Approval for BsAbs in earlier lines of therapy in myeloma and other solid tumors currently being explored and will also contribute to this growing need, Nooka stated. “I would say, learn how to give these safely so that you are ahead of the game. This way the patient is able to get these drugs close to home, which in turn will be very beneficial for their quality of life,” Nooka said.

REFERENCES

1. Firestone R, Lesokhin AM, Usmani SZ. An embarrassment of riches: three FDA-approved bispecific antibodies for relapsed refractory multiple myeloma. Blood Cancer Discov. 2023;4(6):433-436. doi:10.1158/2643-3230.BCD-23-0176

2. A study of teclistamab in combination with daratumumab and lenalidomide (Tec-DR) and talquetamab in combination with daratumumab and lenalidomide (Tal-DR) in participants with newly diagnosed multiple myeloma (MajesTEC-7). Clinicaltrials.gov. Updated October 24, 2024. Accessed November 27, 2024. https://clinicaltrials.gov/study/NCT05552222

3. Zamagni E, Boccadoro M, Spencer A, et al. MajesTEC-4 (EMN30): a phase 3 trial of teclistamab + lenalidomide versus lenalidomide alone as maintenance therapy following autologous stem cell transplantation in patients with newly diagnosed multiple myeloma. Blood. 2022;140(suppl 1):7289-7291. doi:10.1182/blood-2022-159756

4. Grosicki S, Crafoord J, Koh Y, et al. MagnetisMM-5: an open-label, multicenter, randomized phase 3 study of elranatamab as monotherapy and in combination with daratumumab in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2022;40(suppl 16):TPS8074. doi:10.1200/jco.2022.40.16_suppl.tps8074