You Make the Call: Should a mostly asymptomatic patient with amyloidosis receive systemic therapy?

Morie A. Gertz, MD
Chair, Internal Medicine, Mayo Clinic, Minnesota

This month Morie A. Gertz, MD, discusses whether a mostly asymptomatic patient with amyloidosis should receive systemic therapy.

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CLINICAL DILEMMA

An otherwise asymptomatic 64-year-old woman developed two small lumps on her upper lip. One was excised and found to be a small amyloidoma, specifically AL-kappa by mass spectrometry. While the SPEP was normal, immunofixation identified monoclonal kappa protein. Serum free light chains were 2,585 mg/L and 3.08 mg/L, for kappa and lambda, respectively (kappa-to-lambda ratio of 839.53). She had a normal 24-hour urine protein, and on UPEP there was a gamma spike accounting for 46% of the urine protein. Her bone marrow biopsy showed 20-40% plasma cells and FISH identified a gain at 14q32 (IgH) and a loss at 16q23 (MAF). Her hemoglobin is 12.5 g/dL and her creatinine is 0.70 mg/dL. Her factor X level is 140%. There is no evidence of skeletal lesions or cardiac involvement.

I am tempted to treat her with daratumumab plus CyBorD. However, the elevated kappa level may be due to poor renal clearance from dimerization in light of the discordance between her serum kappa level and the amount of monoclonal protein in her urine. Should her amyloidosis be treated with systemic therapy if the only organ involvement found is two small amyloidomas on her lip? Is close observation an option?

Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.

EXPERT OPINION

This patient represents an individual with very high levels of light chain, no myeloma defining events and no evidence of organ infiltration with light chain amyloid. The natural history of such a patient is not well defined. Although the patient has smoldering multiple myeloma, she remains asymptomatic and has had time to visit three specialists without the development of any new symptoms. There are some patients with AL amyloidosis whose light chains simply do not deposit in the heart, liver, kidney, lung or nerve. These people frequently can remain long-term with amyloid limited to soft tissue such as the skin and the carpal ligament − in this instance, lip nodules that sound more like a nuisance then a problem. When one is uncertain what to do, I think it is good general policy to pause for serialized observation.

As described, we have a snapshot. With close follow-up every six weeks, we can have a movie. This will allow the clinician to determine if the light chain levels are rising over time or if there is a progressive decline in the hemoglobin or rise in urinary protein excretion. It will also allow for the serialized measurement of cardiac biomarkers to exclude any development of cardiac amyloidosis. I think it is a judgmental error to assume that a completely asymptomatic patient should be treated simply because the light chain measurement is elevated. In most of these instances, the duration of the light chain abnormality is unknown and may have preceded the development of the lip nodules by years.

I anticipate this patient will eventually develop a more serious plasma cell dyscrasia requiring intervention, but this may be years in the future. As long as the monitoring schedule is frequent, no harm will come to this patient. Four or five sequential observations will allow one to determine if the plasma cell dyscrasia is stable, slowly progressive, or rapidly progressive pain.

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NEXT MONTH'S CLINICAL DILEMMA

I am taking care of a 38-year-old man with sickle cell trait and end-stage renal disease. He was started on dialysis about 15 years ago and developed joint pains and priapism at that time associated with a drop in his hemoglobin level. He eventually got a renal transplant, after which his symptoms resolved and his hemoglobin level normalized. I first saw him about six months ago, after he had been restarted on dialysis for complaints of joint pain. He also reports occasional priapism. He has been hospitalized frequently for severe pain over the past couple of months. I sent his blood for extended hemoglobinopathy testing to see if there was a variant that was potentially interacting with the S trait, but all that was found was the trait. He has significant anemia (hemoglobin ranging from 6 to 8 g/dL), but has no evidence of hemolysis, and his reticulocyte count has been quite low (20,000-30,000). A bone marrow biopsy came back normal. I have been working with nephrology when adjusting his erythropoietin supplementation, as this is the only explanation for his hypoproliferative anemia that I can come up with. I am struggling to improve either his anemia or his pain symptoms. Are there alternative explanations or interventions I am missing? I don’t see how sickle cell−directed therapy would make sense in this setting, but I can’t think of anything else to offer.

Disclaimer: ASH does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this article is solely at your own risk.