Clinical Scenario

This protocol applies to patients with relapsed and/or refractory multiple myeloma who have completed exactly one prior line of therapy, whose disease is refractory to lenalidomide, who are not refractory to anti-CD38 antibodies, and who are eligible for CAR T cell therapy.

Treatment Approach

When available, a CAR T cell therapy is the preferred approach for eligible patients in this setting. For those where it cannot be accessed, anti-CD38 antibody–based combination regimens represent the preferred class of alternatives — with other combinations available for specific circumstances.

The complete regimen options, selection criteria, and sequencing are detailed in the full structured protocol.

References

DOI: 10.1038/s41571-025-01041-x

Patients eligible for treatment with CAR T cells with disease refractory to first-line lenalidomide and who have not received or have disease sensitive to anti-CD38 antibodies should receive cilta-cel, if available [I, A].
Other options in patients with lenalidomide-refractory disease include DaraKd, IsaKd, BelaPd, BelaVd, DaraPd and SelVd [I, A]; combinations of anti-CD38 antibodies with Kd or BelaPd provide the best outcomes in patients with lenalidomide-refractory MM, and are preferred.
PVd or DaraVd can be used if BelaPd or BelaVd, respectively, are unavailable [panel consensus; I, A].

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What Is the Treatment of Multiple Myeloma Relapsed or Refractory After One Prior Line, When the Disease Is Refractory to Lenalidomide and Eligible for CAR T Cell Therapy?

References