European Collaborative Study Defining Clinical Profile Outcomes and Novel Prognostic Criteria in Monoclonal Immunoglobulin M-Related Light Chain Amyloidosis.
Immunoglobulin M (IgM)-related light chain (AL) amyloidosis, which accounts for 6% to 10% of all AL amyloidosis cases, is a rare and poorly studied clinical entity. Its natural history and management is not clearly defined. Prognostic and response criteria for AL amyloidosis in general have not been validated in this population.



We retrospectively gathered data for 250 patients diagnosed with IgM AL amyloidosis from three European amyloidosis centers. Clinical features, hematologic response, and overall survival (OS) were analyzed. The current staging and response criteria in non-IgM AL amyloidosis was applied to this series to assess its utility in this patient cohort.



Patients with IgM AL amyloidosis have a significant IgM paraprotein (median, 10 g/L), less frequent lambda light chain isotype, and evaluable difference between involved and uninvolved free light chains (dFLCs; > 50 mg/L) in only two thirds of patients. Bone marrow showed clear non-Hodgkin lymphoma as the underlying disorder in 54% of patients. Cardiac involvement (45%) is less common but there is more frequent lymph node (20%) and neuropathic (28%) involvement compared with non-IgM AL. Fifty-seven percent of patients achieved a hematologic response (14% very good partial response/complete response [VGPR/CR]), with median OS not reached for patients achieving VGPR/CR, 64 months for PR, and 28 months for nonresponders (P < .001). On multivariate analysis, cardiac involvement, advanced Mayo disease stage, neuropathic involvement, and liver involvement were independent factors that had an impact on survival. Combining abnormal N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T with liver involvement and the presence of neuropathy gives a better risk model: median OS of patients with none, one, or two or more abnormal factors was 90, 33, and 16 months, respectively.



IgM AL amyloidosis is a distinct clinical entity. Low-risk disease can be defined by combining cardiac involvement with novel prognostic markers. Deeper hematologic responses translate into improved outcomes, yet deep responses remain dismally poor, which highlights the urgent need for novel therapies.
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Sajitha
S
Sachchithanantham
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Murielle
M
Roussel
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Giovanni
G
Palladini
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Catherine
C
Klersy
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Shameem
S
Mahmood
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Christopher Paul
CP
Venner
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Simon
S
Gibbs
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Julian
J
Gillmore
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Helen
H
Lachmann
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Philip N
PN
Hawkins
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Arnaud
A
Jaccard
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia.
Giampaolo
G
Merlini
Sajitha Sachchithanantham, Murielle Roussel, Shameem Mahmood, Julian Gillmore, Helen Lachmann, Philip N. Hawkins, and Ashutosh D. Wechalekar, University College London Medical School, London, United Kingdom; Murielle Roussel, Centre Hospitalier Universitaire (CHU) Purpan, Toulouse; Arnaud Jaccard, CHU Limoges, Limoges, France; Giovanni Palladini and Giampaolo Merlini, University of Pavia; Catherine Klersy, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia, Italy; Christopher Paul Venner, University of Alberta, Edmonton, Alberta, Canada; and Simon Gibbs, Westmead Hospital, Sydney, New South Wales, Australia. a.wechalekar@ucl.ac.uk.
Ashutosh D
AD
Wechalekar
D000368:Aged; D000686:Amyloidosis / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies
D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M