Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis

Long-term results from a phase 2 trial

Shaji K Kumar, Suzanne R. Hayman, Francis K. Buadi, Vivek Roy, Martha Lacy, Morie Gertz, Jacob Allred, Kristina M. Laumann, Peter Leif Bergsagel, David M Dingli, Joseph R Mikhael, Craig B. Reeder, Alexander Keith Stewart, Steven R. Zeldenrust, Philip R. Greipp, John A. Lust, Rafael Fonseca, Stephen J Russell, S Vincent Rajkumar, Angela Dispenzieri

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Light-chain (AL) amyloidosis remains incurable despite recent therapeutic advances. Given the activity of the lenalidomidealkylating agent combination in myeloma, we designed this phase 2 trial of lenalidomide, cyclophosphamide, and dexamethasone in AL amyloidosis. Thirty-five patients, including 24 previously untreated, were enrolled. Nearly one-half of the patients had cardiac stage III disease and 28% had ≥ 3 organs involved. The overall hematologic response (≥ partial response [PR]) rate was 60%, including 40% with very-good partial response or better. Using serum-free light chain for assessing response, 77% of patients had a hematologic response. Organ responses were seen in 29% of patients and were limited to those with a hematologic response. The median hematologic progressionfree survival was 28.3 months, and the median overall survival was 37.8 months. Hematologic toxicity was the predominant adverse event, followed by fatigue, edema, and gastrointestinal symptoms. A grade 3 or higher toxicity occurred in 26 patients (74%) including ≥ grade 3 hematologic toxicity in 16 patients (46%) and ≥ grade 3 nonhematologic toxicity in 25 patients (71%). Seven patients (20%) died on study, primarily because of advanced disease. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) is an effective combination for treatment of AL amyloidosis and leads to durable hematologic responses as well as organ responses with manageable toxicity. The trial was registered at www.clinicaltrials.gov (NCT00564889).

Original languageEnglish (US)
Pages (from-to)4860-4867
Number of pages8
JournalBlood
Volume119
Issue number21
DOIs
StatePublished - May 24 2012

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Amyloidosis
Cyclophosphamide
Dexamethasone
Toxicity
Light
Survival
lenalidomide
Fatigue of materials
Fatigue
Edema
Therapeutics
Serum

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis : Long-term results from a phase 2 trial. / Kumar, Shaji K; Hayman, Suzanne R.; Buadi, Francis K.; Roy, Vivek; Lacy, Martha; Gertz, Morie; Allred, Jacob; Laumann, Kristina M.; Bergsagel, Peter Leif; Dingli, David M; Mikhael, Joseph R; Reeder, Craig B.; Stewart, Alexander Keith; Zeldenrust, Steven R.; Greipp, Philip R.; Lust, John A.; Fonseca, Rafael; Russell, Stephen J; Rajkumar, S Vincent; Dispenzieri, Angela.

In: Blood, Vol. 119, No. 21, 24.05.2012, p. 4860-4867.

Research output: Contribution to journalArticle

Kumar, Shaji K ; Hayman, Suzanne R. ; Buadi, Francis K. ; Roy, Vivek ; Lacy, Martha ; Gertz, Morie ; Allred, Jacob ; Laumann, Kristina M. ; Bergsagel, Peter Leif ; Dingli, David M ; Mikhael, Joseph R ; Reeder, Craig B. ; Stewart, Alexander Keith ; Zeldenrust, Steven R. ; Greipp, Philip R. ; Lust, John A. ; Fonseca, Rafael ; Russell, Stephen J ; Rajkumar, S Vincent ; Dispenzieri, Angela. / Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis : Long-term results from a phase 2 trial. In: Blood. 2012 ; Vol. 119, No. 21. pp. 4860-4867.
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abstract = "Light-chain (AL) amyloidosis remains incurable despite recent therapeutic advances. Given the activity of the lenalidomidealkylating agent combination in myeloma, we designed this phase 2 trial of lenalidomide, cyclophosphamide, and dexamethasone in AL amyloidosis. Thirty-five patients, including 24 previously untreated, were enrolled. Nearly one-half of the patients had cardiac stage III disease and 28{\%} had ≥ 3 organs involved. The overall hematologic response (≥ partial response [PR]) rate was 60{\%}, including 40{\%} with very-good partial response or better. Using serum-free light chain for assessing response, 77{\%} of patients had a hematologic response. Organ responses were seen in 29{\%} of patients and were limited to those with a hematologic response. The median hematologic progressionfree survival was 28.3 months, and the median overall survival was 37.8 months. Hematologic toxicity was the predominant adverse event, followed by fatigue, edema, and gastrointestinal symptoms. A grade 3 or higher toxicity occurred in 26 patients (74{\%}) including ≥ grade 3 hematologic toxicity in 16 patients (46{\%}) and ≥ grade 3 nonhematologic toxicity in 25 patients (71{\%}). Seven patients (20{\%}) died on study, primarily because of advanced disease. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) is an effective combination for treatment of AL amyloidosis and leads to durable hematologic responses as well as organ responses with manageable toxicity. The trial was registered at www.clinicaltrials.gov (NCT00564889).",
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AU - Kumar, Shaji K

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AU - Buadi, Francis K.

AU - Roy, Vivek

AU - Lacy, Martha

AU - Gertz, Morie

AU - Allred, Jacob

AU - Laumann, Kristina M.

AU - Bergsagel, Peter Leif

AU - Dingli, David M

AU - Mikhael, Joseph R

AU - Reeder, Craig B.

AU - Stewart, Alexander Keith

AU - Zeldenrust, Steven R.

AU - Greipp, Philip R.

AU - Lust, John A.

AU - Fonseca, Rafael

AU - Russell, Stephen J

AU - Rajkumar, S Vincent

AU - Dispenzieri, Angela

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N2 - Light-chain (AL) amyloidosis remains incurable despite recent therapeutic advances. Given the activity of the lenalidomidealkylating agent combination in myeloma, we designed this phase 2 trial of lenalidomide, cyclophosphamide, and dexamethasone in AL amyloidosis. Thirty-five patients, including 24 previously untreated, were enrolled. Nearly one-half of the patients had cardiac stage III disease and 28% had ≥ 3 organs involved. The overall hematologic response (≥ partial response [PR]) rate was 60%, including 40% with very-good partial response or better. Using serum-free light chain for assessing response, 77% of patients had a hematologic response. Organ responses were seen in 29% of patients and were limited to those with a hematologic response. The median hematologic progressionfree survival was 28.3 months, and the median overall survival was 37.8 months. Hematologic toxicity was the predominant adverse event, followed by fatigue, edema, and gastrointestinal symptoms. A grade 3 or higher toxicity occurred in 26 patients (74%) including ≥ grade 3 hematologic toxicity in 16 patients (46%) and ≥ grade 3 nonhematologic toxicity in 25 patients (71%). Seven patients (20%) died on study, primarily because of advanced disease. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) is an effective combination for treatment of AL amyloidosis and leads to durable hematologic responses as well as organ responses with manageable toxicity. The trial was registered at www.clinicaltrials.gov (NCT00564889).

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