Sajitha Sachchithanantham1, Murielle Roussel1, Giovanni Palladini1, Catherine Klersy1, Shameem Mahmood1, Christopher Paul Venner1, Simon Gibbs1, Julian Gillmore1, Helen Lachmann1, Philip N Hawkins1, Arnaud Jaccard1, Giampaolo Merlini1, Ashutosh D Wechalekar2. 1. 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. 2. 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.
Abstract
PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: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. CONCLUSION: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.
Authors: Surbhi Sidana; Surendra Dasari; Taxiarchis V Kourelis; Angela Dispenzieri; David L Murray; Rebecca L King; Ellen D McPhail; Marina Ramirez-Alvarado; Shaji K Kumar; Morie A Gertz Journal: Blood Adv Date: 2021-04-27
Authors: Jahanzaib Khwaja; Shirley D'Sa; Monique C Minnema; Marie José Kersten; Ashutosh Wechalekar; Josephine M Vos Journal: Haematologica Date: 2022-09-01 Impact factor: 11.047