Prognostic impact of serial measurements of serum-free light chain assay throughout the course of newly diagnosed multiple myeloma treated with bortezomib-based regimens

Abstract

We retrospectively investigated the role of serial serum-free light chain (sFLC) evaluations in 150 multiple myeloma (MM) patients treated with first-line bortezomib-based regimens. Baseline sFLC ratio (sFLCR) identified three groups of patients - normal, lightly abnormal (<100), and highly abnormal (≥100) - with different progression-free survival (PFS: 3-year estimate 72% versus 61% versus 44%, respectively, p = 0.03). Moreover, the achievement of a normal sFLCR correlated with extended PFS (49 versus 17 months, p < 0.0001) and overall survival (75 versus 43 months, p < 0.0001) as compared with abnormal sFLCR, a gain maintained in a multivariate analysis for PFS. At relapse, a high sFLCR was associated with earlier start of salvage therapy compared with sFLCR <100 (3-month probability: 89% versus 64%, p = 0.0426). In 20% of patients, sFLC escape preceded the conventional relapse by a median of 3.8 months. Our results highlight the role of sFLC assay in the prognosis and follow-up of MM.

Prognostic impact of rapid reduction of involved free light chains in multiple myeloma patients under first-line treatment with Bendamustine, Prednisone, and Bortezomib (BPV)

“…In the era of conventional chemotherapy, Dispenzieri et al (2008) demonstrated that patients with sFLC values above 117 mg/L had significantly shorter PFS and OS. After the introduction of the new drugs especially bortezomib-containing combinations, the Italian study group of Tacchetti et al (2016) found that PFS, but not OS was reduced in patients with sFLC levels above 100 mg/L. This contrasts to our observation that neither sFLC nor sFLCr showed an impact on PFS or OS.…”

Role of serum free light chain assay in the detection of early relapse and prediction of prognosis after relapse in multiple myeloma patients treated upfront with novel agents

“…Lastly, we found that an sFLCR of 120 or more at relapse predicted for poor outcomes and retained independent prognostic value in a multivariate analysis. These data further support the evidence that elevated sFLC levels correlate with more aggressive clinical outcomes of MM, 9,12,13 and suggest the possibility of using a high sFLCR to identify relapsed MM patients who are at high risk of developing imminent organ damage, and who are, therefore, to be considered eligible for prompt salvage treatment.…”

“…1,3,4 Nonetheless, sFLC assay might be an appropriate tool also in secretory MM, since an imbalance in sFLCR can be detected in approximately 90% of patients with Ig-secretory MM (Ig-MM) 5 and in almost all patients with light chain MM (LC-MM). 6 Moreover, it is well recognized that sFLC escape might occur before, or at the time of, relapse [7][8][9] and increasing levels of sFLC at progression have been reported to predict a worse prognosis. 7 However, most of these studies are biased by the lack of serial assay measurements.…”

Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting

“…Furthermore, the variability in FLC levels/ratio in patients with non-secretory MM 45 and differences in FLC/light chain development during follow-up in non-secretory patients 46 may result in challenges for interpretation of response and progression. Serum FLC ratio is prognostic for PFS and OS in MM, but discrepancies have been reported in FLC-based relapse versus conventional relapse, with serum FLC escape occurring a median of 3.8 months earlier than conventional relapse in 20% of patients in one retrospective investigation 47 . Thus, there is a potential impact on the interpretation of overall outcomes between studies that include or exclude FLC-only evaluable patients.…”