Dr Rajkumar Previews ASCO 2024 Data in Multiple Myeloma

S. Vincent Rajkumar, MD, professor, medicine, Mayo Clinic College of Medicine, chair, Mayo Clinic Myeloma, Amyloidosis, and Dysproteinemia Group, discusses highly anticipated abstracts in multiple myeloma that will be presented at the 2024 ASCO Annual Meeting.

At the 2024 ASCO Annual Meeting, findings from several pivotal randomized controlled trials in multiple myeloma are set to be presented for the first time, promising to provide new insights and potentially alter the treatment paradigm in myeloma, Rajkumar begins. Four key trials are of particular interest, 2 of which focus on the use of isatuximab (Sarclisa)–based regimens in the frontline setting for patients with newly diagnosed transplant-ineligible multiple myeloma, he says. The first is a randomized phase 3 study (NCT04751877) of isatuximab plus lenalidomide (Revlimid) and dexamethasone (Rd) with bortezomib (Velcade; Isa-VRd) vs Isa-Rd alone in patients between 65 and 80 years of age. The second trial, the phase 3 IMROZ study (NCT03319667), will compare Isa-VRd with standard-of-care (SOC) VRd.

Data from the randomized phase 3 DREAMM-8 study (NCT04484623) will also be presented, Rajkumar continues. This study assessed belantamab mafodotin (Blenrep) plus pomalidomide (Pomalyst) and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in patients with relapsed/refractory multiple myeloma. These data are particularly noteworthy as the marketing authorization for belantamab mafodotin in this patient population was previously withdrawn following the results of the phase 3 DREAMM-3 trial (NCT04162210), which did not meet its primary end point of a progression-free survival (PFS) benefit with BPd vs PVd, Rajkumar notes. However, new data from DREAMM-8 may shed light on the potential advantages of BPd in the relapsed/refractory patient population, Rajkumar says.

Another significant trial being presented is the phase 3 CANOVA study (NCT03539744), which compared venetoclax (Venclexta) plus dexamethasone vs pomalidomide plus dexamethasone in patients with t(11;14)-positive, relapsed/refractory multiple myeloma, Rajkumar details. Despite initial setbacks in the development of venetoclax from the phase 3 BELLINI trial (NCT02755597), there is hope that new data will provide a clearer picture of venetoclax's efficacy and safety, he adds.

In addition to these phase 3 trials, a phase 2 trial on the real-world schedule de-escalation of teclistamab (Tecvayli) in patients with relapsed/refractory multiple myeloma from Memorial Sloan Kettering will be presented, Rajkumar reports. This study aims to address concerns regarding the tolerability of the current teclistamab dosing schedule for this patient population. Additionally, a real-world study comparing the efficacy of the BCMA-targeted therapy linvoseltamab (REGN5458) vs SOC in patients with triple-class exposed relapsed/refractory multiple myeloma in the United States will be discussed, he adds.

Research on predictors of response to BCMA-based CAR T-cell therapy is also advancing, with a study from the University of Arkansas for Medical Sciences investigating T-cell subsets to predict treatment outcomes, Rajkumar says. Lastly, the MRD2STOP study (NCT04108624) from the University of Chicago will explore the feasibility of using minimal residual disease to determine when maintenance therapy can be safely discontinued in patients with multiple myeloma, addressing the ongoing challenge of the increasing cost and duration of treatment in this disease, Rajkumar explains.

These trials, especially those investigating quadruplet regimens in non–transplant eligible patients, will provide valuable data on both efficacy and safety, potentially influencing future clinical practices in the treatment of patients with multiple myeloma, he concludes.