• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Table 11Summary of findings for KQs 15

KQStrength of EvidenceSummary, Comments, and Conclusions
KQ1: Do the SFLC assay and the SFLC ratio improve diagnostic accuracy for PCDs when combined with traditional tests, compared with traditional tests alone, in undiagnosed patients with suspected PCD?Insufficient (favoring use of the SFLC assay and ratio)Three retrospective studies (all quality B) directly evaluated the SFLC assay in the context of diagnosing PCDs. All 3 compared test results with the diagnosis of disease verified by medical records. Although these studies showed an increase in sensitivity with the addition of the SFLC assay, owing to the heterogeneity in design, patient selection, and comparators used, meta-analysis could not be performed. The effect on specificity was inconsistent.
Conclusions: The SFLC assay appears to increase the sensitivity for diagnosis of PCD, although the effect on specificity was inconsistent. We rated the strength of evidence as insufficient, favoring the addition of the SFLC assay and ratio to the diagnostic test panel for PCDs.
KQ2: As compared with traditional tests, how well does the SFLC assay independently predict progression to MM in patients with MGUS?InsufficientNo studies directly compared the use of the SFLC assay with traditional tests to determine whether it provided better prediction of progression to MM
Conclusions: Owing to the lack of directly applicable data, we rated the evidence as insufficient.
KQ3: In patients with an existing diagnosis of PCD, does the use of the SFLC assay result in different treatment decisions with regard to timing, type, or duration of therapy as compared with traditional tests?InsufficientNo studies directly compared the use of the SFLC assay with traditional tests to determine whether treatment decisions were different with regard to timing, duration, or type of treatment.
Conclusions: Owing to the lack of directly applicable data, we rated the evidence as insufficient.
KQ4: In PCD patients, is the SFLC assay a better indicator of response to treatment, and of outcomes (overall survival, disease-free survival, remission, light chain escape, and quality of life) than traditional tests?Insufficient for SFLC response as a better predictor of survival than M protein response in AL amyloidosis and in MM; also insufficient for other outcomes specifiedOne prospective study, 10 retrospective studies, and 1 study of unclear design (3 quality B, 8 quality C) evaluated the SFLC assay used in parallel with traditional tests in relationship to clinical outcomes, including survival. Three studies were in patients with AL amyloidosis and evaluated response to treatment as a predictor of outcomes; the other 8 studies were in patients with MM and evaluated either responses of SFLC or M protein to treatment or baseline levels of SFLC or M protein as predictors of clinical outcomes.
The 3 retrospective studies in AL amyloidosis showed that patients with greater reductions in abnormal SFLC concentrations (a >50% or >90% reduction, vs. lesser reductions) after treatment (either chemotherapy or stem-cell transplantation) had better survival outcomes. The relationship between quantitative reduction in M protein and outcomes was inconsistent across studies. The prevalence of measurable disease limited the use of the SFLC assay, precluding its utility in patients without elevated levels before treatment.
Five of the 8 studies that enrolled patients with MM addressed the use of SFLC assay in the assessment or prediction of treatment response. The traditional test comparators differed in each study. Four of the studies included patients who achieved an SFLC response earlier than a response by traditional tests; 2 examined the relationship between baseline SFLC concentrations and survival; 3 examined the relationship between post-treatment SFLC level and survival. Studies that addressed changes in SFLC or M protein relative to survival showed conflicting results.
Conclusions: Although SFLC response to therapy appeared to be a consistent predictor of outcomes in AL amyloidosis, there was no evidence that the SFLC assay is superior to traditional tests, as direct comparisons were unavailable. Similarly, there was no evidence to ascertain whether SFLC response was a better predictor of outcomes than traditional tests in MM. We rated the strength of evidence as insufficient for the SFLC response as a better predictor of survival in AL amyloidosis and insufficient for the SFLC response as a better predictor of survival in MM.
KQ5: In PCD patients, does the use of the SFLC assay reduce the need for other diagnostic tests (e.g., bone marrow biopsy)?Insufficient to support that use of the SFLC assay reduces the need for other diagnostic testsOne study (quality C) addressed this question.
The study is a retrospective review of patients with a negative IFE test after treatment of MM who had a concomitant evaluable bone marrow aspiration or biopsy. A subset of patients also had data on the SFLC ratio; among those whose ratio normalized, the percentage of clonal plasma cells in the bone marrow was examined. A total of 14% of patients with a negative IFE test had ≥5% plasma cells in bone marrow, as did10% with a normal SFLC ratio.
The authors recommended that, even if the SFLC assay is used, bone marrow examination should not be eliminated for the assessment of response.

AL amyloidosis=systemic amyloidosis in which amyloid [A] proteins derived from immunoglobulin light chains [L] are deposited in tissue, IFE=immunofixation electrophoresis, KQ=Key Question, MGUS=monoclonal gammopathy of undetermined significance, MM=multiple myeloma, PCD=plasma cell dyscrasia, SFLC=serum free light chain.

From: Discussion

Cover of Serum Free Light Chain Analysis for the Diagnosis, Management, and Prognosis of Plasma Cell Dyscrasias
Serum Free Light Chain Analysis for the Diagnosis, Management, and Prognosis of Plasma Cell Dyscrasias [Internet].
Comparative Effectiveness Reviews, No. 73.
Rao M, Yu WW, Chan J, et al.

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.