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IMWG sequencing recommendations
The availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy. The IMWG summarized existing information on sequencing therapy and provided a series of core recommendations.
Prior therapy and optimization
- Patients can proceed to TCR with no concern following treatment with any combination of PI, immunomodulatory drug, mAb or corticosteroid
- Considerations for TCR (CAR-T therapy and TCE)
- Aim for a 2-week washout between last dose of PI, immunomodulatory drug, mAb and apheresis
- Avoid high-dose alkylators and bendamustine prior to TCR
- Considerations for CAR-T therapy
- Aim for a 4-week washout from TCE or collect cells prior to TCE initiation
- Assuming equal access:
- Pursue BCMA-targeted TCR ahead of BCMA-targeted ADC given its higher efficacy
- Pursue BCMA-targeted CAR-T therapy ahead of BCMA-targeted TCE
- More robust data support activity of TCEs following relapse post-CAR-T therapy than vice versa
- Extended TFI with CAR-T therapy is associated with more salvage options
- Both BCMA- and GPRC5D-targeted immunotherapy are safe and active in patients with prior BCMA-targeted CAR-T therapy however responses to BCMA-targeting therapies are likely less frequent and durable
- For patients progressing on a BCMA-targeting TCE, recommend therapy with a different MOA or target
- Strongly consider bridging therapy in patients with high disease burden or at risk of mortality in the CAR-T manufacturing period
- Ideal bridging therapy will contain an agent(s) the patient is not resistant to, will be short and with low risk of infection/prolonged cytopenias
- Prioritize TCE over CAR-T therapy for faster access in patients with rapidly progressing disease at risk of mortality in the CAR-T manufacturing period
ADC, antibody-drug conjugate; BCMA, B-cell maturation antigen; CAR-T, chimeric antigen receptor T cell; GPRC5D, G protein-coupled receptor class C, group 5, member D; IMWG, International Myeloma Working Group; LOT, line of therapy; mAb, monoclonal antibody; MOA, mechanism of action; PI, proteasome inhibitor; TCE, T-cell engager; TCR, T-cell redirection therapy; TFI, treatment-free interval.
Costa LJ, et al. Leukemia. 2025;1–12.
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