Selection of multiple myeloma therapy at third or later relapse

There is no single standard therapy for relapsed or refractory MM and practice varies widely; as such, we encourage eligible patients to participate in clinical trials. This algorithm illustrates our approach to systemic therapy in patients with third or greater relapse of MM. Other regimens are available and may be used by other experts. The choice for an individual must take into account expected toxicities, comorbidities, and drug accessibility.

BCMA: B cell maturation antigen; CAR: chimeric antigen receptor; Cilta-cel: ciltacabtagene autoleucel; DCEP: dexamethasone, cyclophosphamide, etoposide, and cisplatin; Ide-cel: idecabtagene vicleucel; MM: multiple myeloma; VDT-PACE: bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, and etoposide.

* We use the following cutoffs to define refractory and not refractory MM to guide therapy:

Refractory: Progression within 60 days of exposure to an agent at standard doses
Sensitive: Progression >60 days from last exposure or progression on minimal therapy (eg, lenalidomide 10 mg or monthly daratumumab)

¶ When selecting a regimen, avoid agents that the MM is refractory to and prioritize regimens that contain two drugs that the MM has not been exposed to.

Δ Options include CAR-T cell therapy (ide-cel or cilta-cel) or a BCMA/CD3 bispecific antibody (teclistamab or elranatamab). A choice is individualized weighing disease tempo, availability, and expected toxicity. As an off-the-shelf option, bispecific antibodies may be preferred in rapidly progressing disease unlikely to be controlled while awaiting CAR-T cell manufacturing.

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Selection of multiple myeloma therapy at third or later relapse