Comparing measures of hematologic response after high-dose melphalan and stem cell transplantation in AL amyloidosis

Abstract

Hematologic complete response (hemCR) in AL amyloidosis requires absence of monoclonal protein by immunofixation electrophoreses (IFE) and normal serum free light chain ratio (FLCR). Recent literature suggests that an involved free light chain (iFLC) <20 mg/L or difference in free light chains (dFLC) <10 mg/L may more accurately predict outcomes after treatment. We evaluated overall survival in 340 patients treated with high-dose melphalan and stem cell transplantation (SCT). Of 305 patients evaluable 6 months after SCT, 90 (30%) achieved hemCR, 132 (43%) dFLC <10 mg/L, 118 (39%) iFLC <20 mg/L, and 176 (58%) normal FLCR. Of 215 patients without hemCR, 65 (30%) had dFLC <10 mg/L and 86 (40%) had normal FLCR. Overall survival (OS) in those achieving dFLC <10 mg/L or normal FLCR without hemCR was inferior to those achieving hemCR (p = 0.013 and p = 0.001). OS was not significantly different in patients achieving iFLC <20 mg/L without hemCR compared with hemCR (p = 0.243). Of those with hemCR, OS was not significantly improved if dFLC <10 mg/L was also achieved (p = 0.852), but OS was improved for those with hemCR who also attained iFLC <20 mg/L (p = 0.009). Multivariate analysis demonstrated absence of monoclonal protein in IFE and iFLC <20 mg/L as independent predictors of survival. Attainment of hemCR remains a treatment goal, although achieving iFLC <20 mg/L may also predict improved OS.

Minimal residual disease negativity by next-generation flow cytometry is associated with improved organ response in AL amyloidosis

“…The size of the underlying PC clone at baseline affects prognosis 5 . Profound decreases of LC levels through PC-targeting chemotherapy can result in the improved organ dysfunction and arrest the otherwise inexorable progression of the disease 6 – 10 . After treatment, even small increases in amyloid LCs can cause organ progression and reduced survival 11 .…”

Characterization and prognostic implication of delayed complete response in AL amyloidosis

“…We and others recently re-assessed the definition of the conventional hematological CR definition. [14][15][16] In these studies, both the ratio) were found to be important from survival standpoint. [14][15][16] However, the quantitative light chain component (expressed as iFLC < 20 mg/L or dFLC < 10 mg/L) directly impacts the organ dys- 17 and marrow MRD assessment.…”

“…[14][15][16] In these studies, both the ratio) were found to be important from survival standpoint. [14][15][16] However, the quantitative light chain component (expressed as iFLC < 20 mg/L or dFLC < 10 mg/L) directly impacts the organ dys- 17 and marrow MRD assessment. 8,[18][19][20][21][22] Alternatively, better ways to predict delayed CR among deep responders, using baseline immunologic, or genetic profiling and at EOT should also be explored.…”

“…However, as shown in this study, CR may still not be achieved at EOT by the conventional definition, but outcome remains favorable if CR is eventually achieved in a delayed fashion. We and others recently re‐assessed the definition of the conventional hematological CR definition 14‐16 . In these studies, both the immunofixation component of the CR definition as well as its light chain component (whether quantitative measure or the light chain ratio) were found to be important from survival standpoint 14‐16 .…”

“…We and others recently re‐assessed the definition of the conventional hematological CR definition 14‐16 . In these studies, both the immunofixation component of the CR definition as well as its light chain component (whether quantitative measure or the light chain ratio) were found to be important from survival standpoint 14‐16 . However, the quantitative light chain component (expressed as iFLC < 20 mg/L or dFLC < 10 mg/L) directly impacts the organ dysfunction and arguably needs to be achieved early to positively affect survival.…”