Researchers in Italy suggest that MRD positivity may explain persistent organ dysfunction in patients with light chain, or AL, amyloidosis, a rare plasma-cell disorder characterized by the buildup of amyloid protein deposits in tissues and organs. The study, published in February in the Blood Cancer Journal, is thought to be the first to evaluate the incremental clinical significance of MRD monitoring by high-sensitivity next-generation flow cytometry (NGF) in patients with AL amyloidosis who are otherwise in amyloid complete response (aCR).

Using NGF with a minimum sensitivity of 10^-5 (reaching 10^-6 in 76% of cases), Giovanni Palladini, MD, and colleagues at the Amyloidosis Research and Treatment Center in Pavia, Italy, identified persistent MRD in 50 patients (54%) among a cohort of 92 patients who had been confirmed to be in aCR for at least 6 months following treatment discontinuation. Undetectable MRD was associated with improvement of organ involvement following aCR in more than 90% of patients. Undetectable MRD was also associated with higher rates of renal and cardiac response and with longer progression-free survival.

Patients had received either 1 or 2 lines of therapy before achieving aCR. Baseline clinical variables were not significantly different in patients with or without detectable MRD. The number of lines of treatment, the median time from diagnosis to documentation of aCR, and the median time from the first documentation of aCR to MRD assessment did not differ between MRD-positive and MRD-negative patients. Time to hematologic progression was significantly longer in MRD-negative patients; 1 patient with undetectable MRD at a sensitivity of 10^-5 progressed, compared with 13 MRD-positive patients.

The study authors recommend offering MRD assessment to patients with AL amyloidosis who attain aCR, especially if aCR is not accompanied by organ response. If MRD is detected, they suggest considering further chemotherapy while balancing residual organ damage, patient frailty, and possible toxicity.

– Palladini G, Paiva B, Wechalekar A, et al. Minimal residual disease negativity by next-generation flow cytometry is associated with improved organ response in AL amyloidosis. Blood Cancer J. 2021;11(2):34. Published 2021 Feb 16. doi:10.1038/s41408-021-00428-0

Tags: MRD, organ, response, AL amyoidosis, negativity