Management Algorithms for Relapsed/Refractory AL Amyloidosis

Authored by Rajshekhar Chakraborty, published on 2026-04-22 21:19:55.0

The algorithm broadly reflects contemporary relapsed/refractory AL amyloidosis principles: response-adapted switching based on hematologic depth/organ response and selection of subsequent therapy informed by plasma-cell biology (e.g., t(11;14)). However, it leans heavily toward investigational BCMA-targeted approaches and fixed-duration concepts that are not yet standard-of-care in AL and are supported mainly by early-phase/indirect myeloma evidence. The core switch triggers using hematologic response categories and dFLC-based relapse thresholds are generally consistent with major consensus/guideline statements, though specific timing cutoffs (1/3/6 months) can vary by guideline and patient context.

  1. Relapsed/Refractory AL Amyloidosis after Frontline Dara-CyBorD
    • Indications for switching therapy
      • 2 mg/dL as trigger for initiation of new clone-directed Rx
      • t(11;14)-positive
        • Treatment options (t(11;14)-positive)
          Preferred: BCMA BsAb* [off-label or clinical trial] Bcl2 inhibitor [off-label or clinical trial] BCMA CAR T [clinical trial] Alternative/Less Preferred: ASCT BCMA ADC IMiDs [Pom preferred over Len]
      • t(11;14)-negative or unknown
        • Treatment options (t(11;14)-negative or unknown)
          Preferred: BCMA BsAb* [off-label or clinical trial] BCMA CAR T [clinical trial] Alternative/Less Preferred: ASCT BCMA ADC IMiDs [Pom preferred over Len]
  2. * Consider fixed-duration treatment for 6 months
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