Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL)

Nidhi Tandon, Surbhi Sidana, Angela Dispenzieri, Morie Gertz, Martha Lacy, David M Dingli, Francis K. Buadi, Amie L. Fonder, Suzanne R. Hayman, Yi Lisa Hwa, Miriam A. Hobbs, Prashant Kapoor, Wilson Gonsalves, Nelson Leung, Ronald S. Go, John A. Lust, Stephen J Russell, Robert A. Kyle, S Vincent Rajkumar, Shaji K Kumar

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Abstract

Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10-year period (2006-2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n=166; 48.1%) were compared to those who did not (n=179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi-organ involvement (63.3 vs 46.4%; P=.002) and patients in advanced Mayo stage (42.9 vs 32.2%; P=.04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P=.0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P<.0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n=111; 32.2%) versus not (n=2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P<.0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P<.0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.

Original languageEnglish (US)
JournalAmerican Journal of Hematology
DOIs
StateAccepted/In press - 2017

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Amyloidosis
Light
Therapeutics
Survival
Disease-Free Survival
Reading
Creatinine
Multivariate Analysis
Transplants
Serum

ASJC Scopus subject areas

  • Hematology

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Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL). / Tandon, Nidhi; Sidana, Surbhi; Dispenzieri, Angela; Gertz, Morie; Lacy, Martha; Dingli, David M; Buadi, Francis K.; Fonder, Amie L.; Hayman, Suzanne R.; Hwa, Yi Lisa; Hobbs, Miriam A.; Kapoor, Prashant; Gonsalves, Wilson; Leung, Nelson; Go, Ronald S.; Lust, John A.; Russell, Stephen J; Kyle, Robert A.; Rajkumar, S Vincent; Kumar, Shaji K.

In: American Journal of Hematology, 2017.

Research output: Contribution to journalArticle

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title = "Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL)",
abstract = "Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10-year period (2006-2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n=166; 48.1{\%}) were compared to those who did not (n=179; 51.9{\%}). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi-organ involvement (63.3 vs 46.4{\%}; P=.002) and patients in advanced Mayo stage (42.9 vs 32.2{\%}; P=.04) at diagnosis. The median progression free survival [PFS; 38.2 (95{\%}CI; 26.4, 55.4) vs 67.1 (95{\%}CI; 55.8, 88) months; P=.0002] and overall survival [OS; 94.4 (95{\%}CI; 78, 107.1) vs not reached (NR, 95{\%}CI; 116.1, NR) months; P<.0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n=111; 32.2{\%}) versus not (n=2234; 67.8{\%}) showed consistent results [PFS; 27.1 (95{\%}CI; 23, 53.8) vs 63.3 (95{\%}CI; 55.4, 77) months; P<.0001 and OS; 78 (95{\%} CI; 54.6, 98.8) vs NR (95{\%}CI; NR, NR); P<.0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.",
author = "Nidhi Tandon and Surbhi Sidana and Angela Dispenzieri and Morie Gertz and Martha Lacy and Dingli, {David M} and Buadi, {Francis K.} and Fonder, {Amie L.} and Hayman, {Suzanne R.} and Hwa, {Yi Lisa} and Hobbs, {Miriam A.} and Prashant Kapoor and Wilson Gonsalves and Nelson Leung and Go, {Ronald S.} and Lust, {John A.} and Russell, {Stephen J} and Kyle, {Robert A.} and Rajkumar, {S Vincent} and Kumar, {Shaji K}",
year = "2017",
doi = "10.1002/ajh.24919",
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journal = "American Journal of Hematology",
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T1 - Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL)

AU - Tandon, Nidhi

AU - Sidana, Surbhi

AU - Dispenzieri, Angela

AU - Gertz, Morie

AU - Lacy, Martha

AU - Dingli, David M

AU - Buadi, Francis K.

AU - Fonder, Amie L.

AU - Hayman, Suzanne R.

AU - Hwa, Yi Lisa

AU - Hobbs, Miriam A.

AU - Kapoor, Prashant

AU - Gonsalves, Wilson

AU - Leung, Nelson

AU - Go, Ronald S.

AU - Lust, John A.

AU - Russell, Stephen J

AU - Kyle, Robert A.

AU - Rajkumar, S Vincent

AU - Kumar, Shaji K

PY - 2017

Y1 - 2017

N2 - Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10-year period (2006-2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n=166; 48.1%) were compared to those who did not (n=179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi-organ involvement (63.3 vs 46.4%; P=.002) and patients in advanced Mayo stage (42.9 vs 32.2%; P=.04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P=.0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P<.0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n=111; 32.2%) versus not (n=2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P<.0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P<.0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.

AB - Achievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10-year period (2006-2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n=166; 48.1%) were compared to those who did not (n=179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi-organ involvement (63.3 vs 46.4%; P=.002) and patients in advanced Mayo stage (42.9 vs 32.2%; P=.04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P=.0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P<.0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n=111; 32.2%) versus not (n=2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P<.0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P<.0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.

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