RE-RITE: Real-world Evaluation of Response, Implementation and Toxicity of Elranatamab

Elranatamab, a BCMA-targeting bispecific antibody, has emerged as an important treatment option in relapsed/refractory multiple myeloma, with clinically meaningful efficacy in patients with multiple prior lines of therapy. However, its clinical use is associated with a distinct toxicity profile, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and an increased risk of infection. As a result, its implementation requires careful operational planning, particularly during step-up dosing and early-cycle monitoring.

Early clinical trial protocols were heavily influenced by CAR-T cell therapy pathways, with inpatient admission frequently used during step-up dosing to mitigate acute toxicity risk. While this approach prioritises safety, it places substantial demands on inpatient capacity and may not be feasible across all treatment centres. This creates potential inequities in access, particularly in hospitals with limited inpatient oncology infrastructure. In response, delivery models in routine clinical practice have evolved rapidly and now vary substantially, ranging from inpatient initiation to ambulatory day-case pathways and, increasingly, outpatient or hybrid virtual ward-based models. These differences largely reflect local infrastructure, service configuration, and institutional risk tolerance rather than a standardised, evidence-based framework.

Although uptake of elranatamab in clinical practice is increasing, there remains limited high-quality real-world evidence defining the optimal intensity of monitoring and care delivery required to ensure safe and efficient administration. In particular, uncertainty remains regarding the minimum level of monitoring that can be safely implemented without increasing clinically meaningful adverse outcomes, including severe CRS, unplanned hospitalisation, or early treatment discontinuation. This evidence gap has important implications for healthcare capacity and scalability, as more intensive inpatient-based approaches may substantially increase bed utilisation and limit equitable access within resource-constrained systems.

In parallel, approaches to infection prevention and immunoglobulin replacement therapy have evolved during the implementation of elranatamab in routine clinical practice. National practice has shifted from predominantly secondary immunoglobulin replacement strategies towards primary prophylaxis in selected patient groups, with current commissioning supporting immunoglobulin replacement in patients with IgG levels below 4 g/L, even in the absence of a significant infection history. This has resulted in routine, often indefinite immunoglobulin replacement during bispecific antibody therapy. While potentially reducing infection risk, this strategy introduces significant cost and treatment burden, effectively constituting dual long-term therapy with both a bispecific antibody and immunoglobulin replacement. Delivery approaches, including intravenous and subcutaneous administration, may also vary between centres, further contributing to heterogeneity in practice.

The clinical and economic impact of these evolving infection prevention strategies remains poorly defined, particularly in the context of sustained B-cell depletion and infection risk associated with BCMA-directed therapies. This represents an important evidence gap with respect to both patient outcomes and healthcare resource utilisation.

There is substantial variation in elranatamab delivery across routine clinical practice, encompassing tertiary and district general hospitals, differing models of ambulatory care provision, and emerging use of virtual ward infrastructure. This heterogeneity, combined with recent changes in immunoglobulin replacement policy, creates a natural experiment in which real-world implementation strategies and their consequences can be systematically evaluated at scale within a single healthcare system.

Taken together, there is a clear need for a national real-world evaluation to define evidence-based pathways for the safe, efficient, and equitable delivery of elranatamab in routine clinical practice. Specifically, there is a need to determine how different delivery models influence safety outcomes, healthcare resource utilisation, infection burden, and treatment continuity, and how evolving supportive care strategies, including immunoglobulin replacement, modify these outcomes. Addressing these gaps is essential to inform scalable implementation across diverse clinical settings while maintaining patient safety and ensuring equitable access to treatment.

The study population will be RRMM patients receiving elranatamab through NHS funding or compassionate access programmes from 01/01/2024 till 31/12/2026. Patients treated within clinical trials will be excluded.

It will be an Ambispective study with Retrospective and Prospective follow up.