Clinical characteristics and outcome of 318 families with familial monoclonal gammopathy: A multicenter Intergroupe Francophone du Myélome study

Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed...

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Published inAmerican journal of hematology Vol. 98; no. 2; pp. 264 - 271
Main Authors Dumontet, Charles, Demangel, Delphine, Galia, Perrine, Karlin, Lionel, Roche, Laurent, Fauvernier, Mathieu, Golfier, Camille, Laude, Marie‐Charlotte, Leleu, Xavier, Rodon, Philippe, Roussel, Murielle, Azaïs, Isabelle, Doyen, Chantal, Slama, Borhane, Manier, Salomon, Decaux, Olivier, Pertesi, Maroulio, Beaumont, Marie, Caillot, Denis, Boyle, Eileen M., Cliquennois, Manuel, Cony‐Makhoul, Pascale, Doncker, Anne‐Violaine, Dorvaux, Véronique, Petillon, Marie Odile, Fontan, Jean, Hivert, Bénédicte, Leduc, Isabelle, Leyronnas, Cécile, Macro, Margaret, Maigre, Michel, Mariette, Clara, Mineur, Philippe, Rigaudeau, Sophie, Royer, Bruno, Vincent, Laure, Mckay, James, Perrial, Emeline, Garderet, Laurent
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.02.2023
Wiley Subscription Services, Inc
Wiley
Subjects
Age composition
Benign monoclonal gammopathy
Cancer and Oncology
Cancer och onkologi
Child
Chromosome Aberrations
Clinical Medicine
Cytogenetics
Diagnosis
Genetic factors
Hematology
Humans
Immunoglobulins
Klinisk medicin
Medical and Health Sciences
Medical prognosis
Medicin och hälsovetenskap
Monoclonal Gammopathy of Undetermined Significance - diagnosis
Multiple myeloma
Multiple Myeloma - pathology
Paraproteinemias - complications
Paraproteinemias - genetics
Prognosis
Statistics
Tumor cells
Online AccessGet full text
ISSN0361-8609
1096-8652
1096-8652
DOI10.1002/ajh.26785

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Abstract Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full‐blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow‐up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.
AbstractList Abstract Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full‐blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow‐up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.
Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full‐blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow‐up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.
Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full-blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow-up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively infrequent and most series reported in the literature describe a limited number of families. MM rarely occurs in a familial context. MGUS is observed much more commonly, which can in some cases evolve toward full-blown MM. Although recurrent cytogenetic abnormalities have been described in tumor cells of sporadic cases of MM, the pathogenesis of familial MM remains largely unexplained. In order to identify genetic factors predisposing to familial monoclonal gammopathy, the Intergroupe Francophone du Myélome identified 318 families with at least two confirmed cases of monoclonal gammopathy. There were 169 families with parent/child pairs and 164 families with cases in at least two siblings, compatible with an autosomal transmission. These familial cases were compared with sporadic cases who were matched for age at diagnosis, sex and immunoglobulin isotype, with 10 sporadic cases for each familial case. The gender distribution, age and immunoglobulin subtypes of familial cases were unremarkable in comparison to sporadic cases. With a median follow-up of 7.4 years after diagnosis, the percentage of MGUS cases having evolved to MM was 3%. The median overall survival of the 148 familial MM cases was longer than that of matched sporadic cases, with projected values of 7.6 and 16.1 years in patients older and younger than 65 years, respectively. These data suggest that familial cases of monoclonal gammopathy are similar to sporadic cases in terms of clinical presentation and carry a better prognosis.
Author Rodon, Philippe
Cliquennois, Manuel
Pertesi, Maroulio
Vincent, Laure
Galia, Perrine
Azaïs, Isabelle
Dorvaux, Véronique
Caillot, Denis
Maigre, Michel
Karlin, Lionel
Leyronnas, Cécile
Golfier, Camille
Rigaudeau, Sophie
Garderet, Laurent
Roussel, Murielle
Cony‐Makhoul, Pascale
Fontan, Jean
Slama, Borhane
Mineur, Philippe
Macro, Margaret
Royer, Bruno
Roche, Laurent
Mariette, Clara
Perrial, Emeline
Decaux, Olivier
Doyen, Chantal
Hivert, Bénédicte
Leduc, Isabelle
Fauvernier, Mathieu
Laude, Marie‐Charlotte
Leleu, Xavier
Doncker, Anne‐Violaine
Beaumont, Marie
Manier, Salomon
Petillon, Marie Odile
Dumontet, Charles
Demangel, Delphine
Boyle, Eileen M.
Mckay, James
AuthorAffiliation 2 CRCL, UMR INSERM 1052/CNRS 5286/University of Lyon‐France Lyon France
23 Hematology Department CHU Caen Caen France
5 IUC‐Oncopôle Toulouse France
4 Hematology Department CH Périgueux Périgueux France
30 HU PITIE SALPETRIERE APHP Paris France
13 Clinical Hematology Department Hôpital F. Mitterrand, CHU Dijon Dijon France
15 Hospitals Organization of Catholic Institute Lille France
1 Hospices Civils de Lyon Lyon France
11 Department of Laboratory Medicine Hematology and Transfusion Medicine Lund Sweden
27 Hematology Department CH Versailles Versailles France
28 Clinical Hematology and Cell Therapy Department Amiens France
14 Perlmutter Cancer Center NYU Langone Health New York New York USA
18 Clinical Hematology Department CHR Metz‐Thionville Metz‐Thionville France
24 Internal Medicine Department CH Chartres Chartres France
9 Hematology Department CHU Rennes, Inserm UMR1236 Rennes France
10 Genetic Cancer Susceptibility, International Agency for Research on Cancer Lyon France
25 Hematology Department
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Snippet Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively...
Abstract Familial forms of monoclonal gammopathy, defined as multiple myeloma (MM) or Monoclonal Gammopathy of Undetermined Significance (MGUS), are relatively...
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SubjectTerms Age composition
Benign monoclonal gammopathy
Cancer and Oncology
Cancer och onkologi
Child
Chromosome Aberrations
Clinical Medicine
Cytogenetics
Diagnosis
Genetic factors
Hematology
Humans
Immunoglobulins
Klinisk medicin
Medical and Health Sciences
Medical prognosis
Medicin och hälsovetenskap
Monoclonal Gammopathy of Undetermined Significance - diagnosis
Multiple myeloma
Multiple Myeloma - pathology
Paraproteinemias - complications
Paraproteinemias - genetics
Prognosis
Statistics
Tumor cells
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Title Clinical characteristics and outcome of 318 families with familial monoclonal gammopathy: A multicenter Intergroupe Francophone du Myélome study
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