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. 2022 Dec;97(12):1607-1615.
doi: 10.1002/ajh.26747. Epub 2022 Oct 18.

Role of serum-free light chain assay for defining response and progression in immunoglobulin secretory multiple myeloma

Paola Tacchetti  1 , Serena Rocchi  1   2 , Elena Zamagni  1   2 , Simona Barbato  1 , Ilaria Rizzello  1   2 , Gabriella De Cicco  1   2 , Lucia Pantani  1 , Katia Mancuso  1   2 , Alessio Fusco  1   2 , Luca Dozza  1 , Margherita Ursi  1   2 , Emanuele Favero  1   2 , Carolina Terragna  1 , Nicoletta Testoni  1   2 , Michele Cavo  1   2
Affiliations

Role of serum-free light chain assay for defining response and progression in immunoglobulin secretory multiple myeloma

Paola Tacchetti et al. Am J Hematol. 2022 Dec.

Abstract

The International Myeloma Working Group (IMWG) guidelines recommend using electrophoresis and immunofixation to define response and progressive disease (PD) in immunoglobulin (Ig) secretory multiple myeloma (Ig-MM), whereas the role of serum-free light chain (sFLC) is controversial. We retrospectively analyzed the value of adding sFLC assays in the definition of response and PD according to IMWG criteria in 339 Ig-MM patients treated with a first-line novel agent-based therapy (median follow-up 54 months). sFLC PD was defined according to conventional criteria plus increased sFLC levels, or sFLC escape (sFLCe); progression/sFLCe-free survival (ePFS) was the time from the start of treatment to the date of first PD or sFLCe, or death; overall survival after PD/sFLCe (OS after Pe) was the time from first PD or sFLCe to the date of death. 148 (44%) patients achieved a complete response and 198 (60%) a normal sFLC ratio (sFLCR). sFLCR normalization was an independent prognostic factor for extended PFS (HR = 0.46, p = 0.001) and OS (HR = 0.47, p = 0.006) by multivariable analysis. 175 (52%) patients experienced PD according to the IMWG criteria, whereas 180 (53%) experienced PD or sFLCe. Overall, a sFLCe was observed in 31 (9%) patients. Median PFS and ePFS were both equal to 36 (95% CI = 32-42, and 32-40, respectively) months. sFLC PD adversely affected the OS after Pe compared to PD with increasing monoclonal Ig only (HR = 0.52, p = 0.012). Our results support the inclusion of the sFLC assay for defining response and PD in Ig-MM.

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Conflict of interest statement

Paola Tacchetti has received Honoraria from Amgen, Bristol‐Myers Squibb/Celgene, Janssen, Takeda, AbbVie, Sanofi, GlaxoSmithKline, and Oncopeptides; Serena Rocchi receives Honoraria from Amgen, GlaxoSmithKline, and Janssen; Elena Zamagni has received honoraria from Janssen, Bristol‐Myers Squibb, Amgen, Takeda; Ilaria Rizzello has received Honoraria from Amgen, GlaxoSmithKline, and Sanofi; Lucia Pantani has received Honoraria from Janssen and Amgen; Katia Mancuso has received Honoraria from Celgene, Takeda, Amgen, Sanofi and Janssen; Michele Cavo has received Honoraria from Janssen, Celgene, Amgen, Bristol‐Myers Squibb, Takeda, AbbVie, Sanofi, Adaptive Biotechnologies, and is a member of Janssen's and Celgene's Speaker's Bureau; Simona Barbato, Gabriella De Cicco, Alessio Fusco, Luca Dozza, Margherita Ursi, Emanuele Favero, Carolina Terragna and Nicoletta Testoni declare no potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Different patterns of progressive disease (PD): (A) Conventionally defined PD, according to IMWG criteria, (B) Modified PD, according to IMWG criteria integrated with sFLC data and including a new subcategory of sFLC PD defined by an increase in sFLC either combined with conventional IMWG criteria of PD or as sFLC escape. M‐Ig, monoclonal immunoglobulin; PD, progressive disease; sFLC, serum‐free light chain. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Flowchart detailing the different patterns of progressive disease. Ig‐MM, immunoglobulin secretory multiple myeloma; M‐Ig, monoclonal immunoglobulin; N°, number; PD, progressive disease; sFLC, serum‐free light chain; sFLCe, serum‐free light chain escape.
FIGURE 3
FIGURE 3
Second time to PD/sFLCe (2nd TTPe) according to the pattern of relapse. CI, confidence interval; M‐Ig, monoclonal immunoglobulin; mos, months; PD, progressive disease; sFLC, serum‐free light chain; sFLCe, serum‐free light chain escape; TTPe, time to PD/sFLCe. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 4
FIGURE 4
Overall survival after PD/sFLCe (OS after Pe) according to the pattern of relapse. CI, confidence interval; M‐Ig, monoclonal immunoglobulin; mos, months; PD, progressive disease; sFLC, serum‐free light chain; sFLCe, serum‐free light chain escape. [Color figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

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