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AL Amyloidosis Key Questions
Key Questions in AL Amyloidosis Care and a Peek Ahead

Released: October 25, 2023

Angela Dispenzieri
Angela Dispenzieri, MD
Ashutosh Wechalekar
Ashutosh Wechalekar, MBBS, MD, FRCP, FRCPath, DM
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Key Takeaways
  • Timely diagnosis and accurate typing of AL amyloidosis, which may be done using mass spectroscopy, is critical for optimizing patient outcomes.
  • The treatment of AL amyloidosis in the relapsed/refractory setting can be challenging and choice of therapy will depend on prior exposures, organ involvement, and cytogenetics.
  • Register and join us live in San Diego or via simulcast on Friday, December 8, 2023 for our upcoming symposium on AL amyloidosis.

Light-chain (AL) amyloidosis is a rare disease that can affect a variety of organ systems. Patients with AL amyloidosis present with nonspecific symptoms that make diagnosis difficult, but timely diagnosis is critical for optimizing patient outcomes. Treatment decisions for managing newly diagnosed and relapsed/refractory AL amyloidosis may be challenging due to the wide variety of treatment options—especially in the relapsed setting—so it is important to stay up to date on the latest data on AL amyloidosis. This commentary features a small sample of questions that we are frequently asked on the diagnosis and management of AL amyloidosis and serves as a preview of the exciting topics we expect to be covered at our upcoming symposium titled, “AL Amyloidosis: Advancements and Future Trends on Diagnosis and Individualized Treatment Approaches” being held at the ASH 2023 annual meeting in December. 

Can a diagnosis of AL amyloidosis be made using traditional tests, such as Congo red stain and immunohistochemistry instead of mass spectroscopy?

Ashutosh Wechalekar, MBBS, MD, FRCP, FRCPath, DM: Congo red staining remains the gold standard for identifying amyloid deposits. However, if not undertaken with appropriate protocols, false positive and false negative results can be seen. Once amyloid deposits have been identified, fibril typing is critically important. Before mass spectroscopy became the standard for diagnosing and typing AL amyloidosis, immunohistochemistry was the standard. These traditional analyses may be appropriate for diagnosis, but there is always an element of uncertainty. However, if a patient has amyloid deposits seen with Congo red staining that are typed as AL with immunohistochemistry in a laboratory with high amyloid tissue volumes and the patient has a light chain excess, we can probably trust those results for treatment purposes. Also, we should keep in mind that immunohistochemistry or immunofluorescence on kidney biopsies are very specific and may be enough for diagnosis. However, the commercially available antibodies for histologic analysis are not uniformly accurate and the reliability of the results may depend on the laboratory performing the tests.

If a patient with AL amyloidosis achieves a VGPR with frontline therapy and has not achieved an organ response, what is your management approach?

Ashutosh Wechalekar, MBBS, MD, FRCP, FRCPath, DM: We are learning that even with VGPR (a differential free light chain of 40 mg/L), there is still more depth of response that is possible. Getting uninvolved free light chain to <10 mg/L has been shown to be associated with better renal and cardiac outcomes. In this setting, if the NT proBNP has plateaued or is going up, one can consider trying to deepen the hematologic response with a change in treatment. The decision on the next steps may also depend on how extensive the organ involvement is. If the patient is modestly symptomatic it may be appropriate to wait a while for additional therapy. For a patient with extensive symptomatic organ involvement with no signs of improvement with a VGPR, then it may be worthwhile to push for a deeper response sooner.

What is the best treatment for patients with AL amyloidosis who experience relapse?

Angela Dispenzieri, MD: Relapsed/refractory AL amyloidosis can be difficult to manage, especially as there are no FDA-approved options in this setting. It is hard to say what the best treatment is, as the choice of therapy will depend on prior exposures, organ involvement, and cytogenetics. Stem cell transplantation may be an option for eligible patients who did not receive a transplant in the newly diagnosed setting. A daratumumab-based therapy was commonly used for second-line management of AL amyloidosis, but with the upfront use of daratumumab, the decision-making process has become more complex. For patients with daratumumab-refractory disease, the immunomodulatory drugs (eg, pomalidomide or lenalidomide) or a proteasome inhibitor like bortezomib or ixazomib are also options. Venetoclax may also be considered for patients with AL Amyloidosis with a t(11;14) translocation. There are also several clinical trials investigating novel agents and combinations for the management of relapsed/refractory AL amyloidosis. Novel agents of interest include venetoclax and other BCL-2 inhibitors, the anti-fibril monoclonal antibodies anselamimab (formerly known as CAEL-101) and birtamimab, and the BCMA-targeting antibody-drug conjugate belantmab mafodotin. The use of cellular therapy in patients with AL amyloidosis is also an area of investigation.

For more information on optimizing AL amyloidosis care, be sure to register and join us live in San Diego or via simulcast on Friday, December 8th, for another exciting symposium on AL amyloidosis. We will cover the most up-to-date guidance on the management of patients with AL amyloidosis and discuss what new data being presented this year at the annual hematology meeting has us most excited. And of course, we’ll be sure to give you ample opportunity to ask us questions. We’re looking forward to seeing you there or online!

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What topic in AL amyloidosis care are you most interested in learning more about at our upcoming symposium at this year’s annual hematology meeting in December?

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