title: Immunoparesis status in immunoglobulin light chain amyloidosis at diagnosis affects response and survival by regimen type.
abstract: Clinical tools to guide in the appropriate treatment selection in immunoglobulin light chain (AL) amyloidosis are not well developed. We evaluated the response and outcome for various regimens at first-line treatment (n=681) and first progression (n=240) stratified by the immunoparesis status at diagnosis. Immunoparesis was assessed by the average relative difference of the uninvolved immunoglobulins, classifying patients into a negative average relative difference (i.e. significant immunoparesis) or a positive average relative difference (no/modest immunoparesis). Treatment was categorized as autologous stem cell transplant and four non-transplant regimens (melphalan-based; bortezomib-based, immunomodulatory drug-based and dexamethasone alone). Patients with significant immunoparesis who underwent stem cell transplant had a significantly lower rate of very good partial response or better response (58%), progression-free survival (median 30 months) and overall survival (108 months), compared to those without significant immunoparesis (80%, 127 months, median not reached, respectively; P<0.001 for all comparisons). Among the non-transplant regimens, melphalan resulted in an unfavorable progression-free survival (11 vs. 27 months; P<0.001) and overall survival (30 vs. 74 months; P=0.001) in patients with significant immunoparesis compared to those without significant immunoparesis. In contrast, no significant difference in outcomes between the immunoparesis groups was seen for those treated with bortezomib or immunomodulatory drugs. At first progression, immunoparesis status did not impact response or survival of any regimen. Melphalan at first-line provided poorer outcomes for patients with significant immunoparesis, while bortezomib or immunomodulatory drugs were more likely to overcome the adverse prognosis associated with significant immunoparesis.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Eli
authors.initials: E
authors.lastname: Muchtar
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Shaji K
authors.initials: SK
authors.lastname: Kumar
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: David
authors.initials: D
authors.lastname: Dingli
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Martha Q
authors.initials: MQ
authors.lastname: Lacy
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Francis K
authors.initials: FK
authors.lastname: Buadi
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Hayman
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kapoor
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
authors.forename: Nelson
authors.initials: N
authors.lastname: Leung
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA Hospitalist services, Essentia Health St. Joseph's Hospital, Brainerd, MN, USA.
authors.forename: Rajshekhar
authors.initials: R
authors.lastname: Chakraborty
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Russell
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Lust
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Go
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Zeldenrust
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA gertz.morie@mayo.edu.
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000175:diagnosis* / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007147:Immunoglobulin Light Chains