Treatment of Relapsed or Refractory Multiple Myeloma After One Prior Line — Bortezomib-Refractory, Lenalidomide-Naive, Anti-CD38-Naive

This protocol covers the management of patients with relapsed and/or refractory multiple myeloma who have received one prior line of therapy, have developed bortezomib-refractory disease, and have not previously been exposed to lenalidomide or an anti-CD38 antibody.

Clinical Scenario The defining profile of this population is relapsed or refractory multiple myeloma following a single prior bortezomib-based line, with confirmed bortezomib-refractory disease. Crucially, neither lenalidomide nor an anti-CD38 antibody has been used previously — a treatment history that directly informs the options now available.

Treatment Approach (partial) For this population, current evidence supports preferred triplet regimens incorporating an anti-CD38 antibody alongside other active agents, with additional approved triplet options available based on individual patient factors. The full regimen selection pathway — including criteria for choosing among alternatives — is available in the complete structured protocol.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1038/s41571-025-01041-x

In patients who have received a bortezomib-based regimen upfront without lenalidomide or an anti-CD38 antibody, and have bortezomib-refractory disease, the preferred regimens are DaraRd, DaraKd and IsaKd [I, A].

Other approved regimens include KRd, IxaRd and elotuzumab (abbreviated as 'Elo' in combinations) plus Rd [I, A].

In patients who have received lenalidomide, BelaPd can also be used [I, A] (Fig. 2).

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