Cellular immunotherapies have transformed relapsed/refractory multiple myeloma (RRMM) treatment, delivering favorable response rates in heavily pretreated populations.1 Despite these achievements, optimal implementation into clinical practice requires thoughtful patient selection, comprehensive evaluation of prior treatments, and effective disease control during the pre-infusion interval.2
Ideal candidates demonstrate preserved functional status, no evidence of severe organ dysfunction, and a disease burden that is manageable during treatment preparation.1,2 Eligibility also depends on the ability to tolerate potential delays between apheresis and infusion as well as to navigate logistical considerations for accessing necessary care. The possibility for outpatient therapy is rapidly evolving, potentially easing these concerns in the future.3 Patients with high disease burden prior to CAR T-cell treatment or with rapid disease progression present unique challenges, as uncontrolled progression during the manufacturing window may preclude infusion.4 Efforts to streamline manufacturing and scheduling have improved access but have not fully eliminated disparities.5
The bridging period between apheresis and infusion requires careful therapeutic management to stabilize disease and preserve eligibility.4,6 This reduction in disease burden also has a possible important impact on the reduction of CAR T-associated toxicities following infusion.4,6There are important considerations for comorbidities that increase risk for adverse events as well; achieving cytoreduction prior to infusion may mitigate cytokine release syndrome and other immune-mediated toxicities.4,6 Despite the remarkable efficacy of cellular therapy, disease progression during bridging remains common, and optimal strategies to minimize this progression while preserving CAR T eligibility and reducing toxicity in RRMM require further investigation.6
Bone marrow assessment prior to, and sometimes following, bridging therapy is often necessary to gauge treatment response and guide intensity.6 One full cycle of bridging therapy is typically recommended prior to CAR T infusion, with a washout of at least seven days between bridging cessation and lymphodepletion.6 This differs from holding therapy where treatment is administered prior to apheresis, and may continue alongside bridging therapy in treatment-responsive patients.6,7
By identifying appropriate candidates, maintaining disease control during preparatory intervals, and preserving mechanistically diverse options for post-cellular therapy management, clinicians can maximize these powerful modalities’ benefits while ensuring comprehensive care throughout the disease trajectory.
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