Welcome back to another Pharmacy Times Practice Pearls series. In this episode titled, 'Rationale and Timing: The Evolving Role of BCMA-Targeted Therapies in Relapsed/Refractory Multiple Myeloma,' Ryan Haumschild led the conversation about the following question: What are the potential clinical benefits and risks of introducing B-cell maturation antigen (BCMA)-targeted therapies earlier in the treatment continuum?

In this episode, 'BCMA Biology, Mechanisms of Action, and Unmet Needs in Relapsed/Refractory Multiple Myeloma,' the expert oncologists and oncology pharmacists explored the following questions: What is the biological rationale for targeting B-cell maturation antigen (BCMA) in multiple myeloma? What are the different types of BCMA-targeted therapies and what are the Food and Drug Administration (FDA)-approved options? How do the mechanisms of action differ for the 3 different types of BCMA-targeted therapies? What unmet needs in relapsed/refractory multiple myeloma (RRMM) are addressed by BCMA-directed therapies? What are the potential clinical benefits and risks of introducing B-cell maturation antigen (BCMA)-targeted therapies earlier in the treatment continuum?

The panelists discussed how BCMA-targeted therapies have rapidly evolved from last-resort options for heavily pretreated patients to agents now considered earlier in the treatment continuum, driven by their remarkable response rates, depth of response, and improving survival outcomes.

Al-Ola Abdallah provided an overview of the DREAMM-7 trial, a multicenter phase 3 study in which belantamab mafodotin plus bortezomib and dexamethasone demonstrated a progression-free survival of approximately 3 years compared with 13 months for the daratumumab plus bortezomib and dexamethasone comparator arm, along with a 42% reduction in the risk of death and higher rates of minimal residual disease (MRD) negativity.

Anjulie Quick explained that belantamab mafodotin affects corneal epithelial cells in addition to myeloma cells, leading to keratopathy and symptoms including decreased vision, dry eye, and photophobia, and outlined the ophthalmologist's critical role within the Risk Evaluation and Mitigation Strategy (REMS) program, which requires baseline eye exams prior to treatment initiation and ongoing examinations before every dose.

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA, highlights key bispecific antibody updates from ASCO and EHA, including updated data from the MajesTEC-6 trial evaluating elranatamab plus daratumumab and lenalidomide in newly diagnosed patients, and the MajesTEC-5 data demonstrating high response rates and minimal residual disease negativity with teclistamab-based induction in transplant-eligible patients, as well as a growing trend toward less frequent dosing schedules to reduce treatment burden and infection risk, and increasing real-world evidence supporting outpatient step-up dosing administration at both academic and community sites.

Zahra Mahmoudjafari emphasized that treatment sequencing in relapsed/refractory multiple myeloma (RRMM) must be highly individualized, taking into account prior BCMA exposure, disease burden, caregiver support, logistical factors, comorbidities, and institutional access to specific therapies such as CAR T-Cell therapy, noting that while a standardized algorithm would be ideal, the complexity of the disease and evolving evidence base make a one-size-fits-all approach impractical.

Zahra Mahmoudjafari noted that while patients with high disease burden, a history of severe cytokine release syndrome (CRS) or neurotoxicity, poor performance status, or limited caregiver support were historically considered less suitable for community-based administration, significant progress has been made as community centers develop strong patient selection criteria, outpatient roadmaps, and escalation strategies, often in partnership with academic centers for initial step-up dosing.

Zahra Mahmoudjafari explained that REMS programs are a Food and Drug Administration (FDA) mechanism designed to ensure that the safety risks associated with specific therapies are clearly communicated to prescribers, healthcare facilities, pharmacies, and patients, noting that each REMS program is unique and that BCMA-directed therapies currently carry REMS requirements for bispecific antibodies due to cytokine release syndrome (CRS) and neurotoxicity risks, and for belantamab mafodotin due to ocular toxicity, while the REMS programs previously required for CAR T-Cell therapies were recently removed.

Al-Ola Abdallah outlined the key adverse events associated with bispecific antibodies, noting that while CRS occurs in over 70% of patients, the majority of cases are grade 1 or 2 and therefore manageable in outpatient settings with appropriate infrastructure, while ICANS is less commonly observed at severe grades compared with CAR T-Cell therapy.

Zahra Mahmoudjafari outlined best practices for pharmacist-led patient education across all three BCMA-directed therapy classes, emphasizing the importance of tailored, proactive counseling that accounts for the unique toxicity profiles of each agent, including cytokine release syndrome (CRS) and neurotoxicity risk with CAR T-Cell therapies and bispecific antibodies, ocular symptoms such as blurred vision and dry eye with belantamab mafodotin, and infection risk across all modalities, while also stressing the critical role of care partners in recognizing and escalating adverse events early.

Zahra Mahmoudjafari expressed optimism about the remarkable evolution of multiple myeloma management over her career while acknowledging the significant responsibility that accompanies the expanding therapeutic landscape, emphasizing the need for operational infrastructure that ensures appropriate access, continued advocacy around Risk Evaluation and Mitigation Strategy (REMS) programs, and strong cross-specialty partnerships such as those with ophthalmology that are critical to safely delivering agents like belantamab mafodotin.