Optimizing Treatment Sequencing Before Third Line CAR T-Cell Therapy in Multiple Myeloma

This segment addresses how clinicians can structure treatment sequencing for patients with relapsed or refractory multiple myeloma who do not receive second line CAR T-cell therapy, drawing on growing evidence from idecabtagene vicleucel studies such as KarMMa and KarMMa 3. Dr. Kaur explains that many patients present later in their disease course, making third line CAR T an important option. One strategy uses a quad regimen followed by a triplet regimen before proceeding to third line CAR T and later bispecific therapy. Advantages include sustained disease control, exposure to multiple active classes, and preserved T cell fitness before CAR T collection. However, patients may accumulate toxicity or progress rapidly, limiting eligibility by the time they reach CAR T. An alternative sequence is a quad regimen followed directly by bispecific therapy. While bispecifics offer rapid off the shelf disease control, prolonged exposure can compromise T cell quality and reduce success of later CAR T manufacturing. Early referral and planning are essential to avoid loss of eligibility and maintain access to both modalities.