Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for ...patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma.
Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival.
After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003).
This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.
Abstract Objective To report on the outcome of 15 cases of pregnancies in women treated with anti-TNF drugs during conception or pregnancy Methods French rheumatologists connecting to the web-site of ...CRI site: http://www.cri-net.com were asked to fill in a structured questionnaire reporting the outcome of pregnancy in women still treated by a TNF blocker at the time of conception. Results Spondylarthropathies ( n = 8), rheumatoid arthritis ( n = 4), juvenile idiopathic arthritis ( n = 2), and psoriatic arthritis ( n = 1) were treated by infliximab ( n = 3), adalimumab ( n = 2), or etanercept ( n = 10). Miscarriages occurred twice, and elective termination was preferred once. Anti-TNF had been administered during the first, second and third trimester of pregnancy in 12, three and two cases. The 12 babies were in good condition, without apparent malformation or symptoms of neonatal illnesses. Conclusion The number of reported cases exceeds 300, but only 29 women were treated during their whole pregnancy. The rate of congenital malformations observed so far might appear reassuring compared to the general population for women exposed only during conception. Conversely, there are too few reports of exposure during pregnancy to allow any conclusion about the safety of TNF blockers, and additional long term follow-up of children would be welcome in order to rule out minor forms of VACTERL association that might have been overlooked at birth.
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.
Imagerie des lésions osseuses du myélome Azaïs, Isabelle; Debiais, Françoise
Revue du rhumatisme monographies,
April 2017, 2017-04-00, Letnik:
84, Številka:
2
Journal Article
Recenzirano
Le myélome multiple (MM) se distingue des autres hémopathies lymphoïdes malignes B par une atteinte osseuse caractéristique : au cours de leur maladie, plus de 80 % des patients souffriront de cette ...ostéolyse myélomateuse ou de ses complications parfois révélatrices. L’évaluation de la maladie osseuse liée au MM est importante : elle participe à la décision d’instauration du traitement antitumoral. Les radiographies standard (mais de plus en plus le scanner corps entier faibles doses) et l’imagerie par résonance magnétique (IRM) conventionnelle pelvirachidienne ou de préférence corps entier restent les examens de référence pour l’évaluation au diagnostic et à la rechute. La tomodensitométrie (TDM) intervient, si nécessaire, en complément. Le rôle de la tomographie par émission de positron (TEP) couplée à la TDM se précise dans l’évaluation de la réponse thérapeutique et le dépistage de la maladie résiduelle. L’avenir précisera le rôle des IRM dynamiques et de diffusion, ou de nouveaux examens d’imagerie en développement tels que la TEP couplée à l’IRM.
Multiple myeloma (MM) differs from other lymphoid B malignancy by its characteristic bone disease. During the course of their MM, up to 80% of patients will suffer from this osteolytic disease or its sometimes-revealing complications. Assessment of MM-related bone disease is important: it can conduct to decide the initiation of antitumoral therapy. Conventional skeletal X-rays (but more and more often whole-body low-dose computed tomography (CT)) and spine and pelvis or preferential whole-body magnetic resonance imaging (MRI) are the gold-standard for the assessment at diagnosis and relapse. If necessary, CT is a complementary imaging method. The role of 18F-fluorodeoxyglucose positron emission tomography (PET)/CT increases in assessment of response to therapy and detection of MM minimal residual disease. Future will clarify the role of diffusion-weighted and dynamic contrast-enhanced MRI or of new imaging technologies such as PET/MRI.
Dexamethasone alone increases life expectancy in patients with relapsed multiple myeloma (MM); however, no large randomized study has compared dexamethasone and dexamethasone-based regimens with ...standard melphalan-prednisone in newly diagnosed MM patients ineligible for high-dose therapy. In the Intergroupe Francophone du Myélome (IFM) 95-01 trial, 488 patients aged 65 to 75 years were randomized between 4 regimens of treatment: melphalan-prednisone, dexamethasone alone, melphalan-dexamethasone, and dexamethasone-interferon alpha. Response rates at 6 months (except for complete response) were significantly higher among patients receiving melphalan-dexamethasone, and progression-free survival was significantly better among patients receiving melphalan (P < .001, for both comparisons), but there was no difference in overall survival between the 4 treatment groups. Moreover, the morbidity associated with dexamethasone-based regimens was significantly higher than with melphalan-prednisone, especially for severe pyogenic infections in the melphalan-dexamethasone arm and hemorrhage, severe diabetes, and gastrointestinal and psychiatric complications in the dexamethasone arms. Overall, these results indicated that dexamethasone should not be routinely recommended as first-line treatment in elderly patients with MM. In the context of the IFM 95-01 trial, the standard melphalan-prednisone remained the best treatment choice when efficacy and patient comfort were both considered. These results might be useful in the context of future combinations with innovative drugs.
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.
Ces dernières années, de nouveaux traitements ont permis une amélioration du pronostic du myélome multiple, mais l’atteinte osseuse reste une préoccupation chez ces patients. L’atteinte osseuse du ...myélome multiple est caractérisée par une augmentation de la résorption osseuse et une diminution de la formation osseuse. Les lésions osseuses au cours de cette affection sont des lésions lytiques, souvent associées avec des douleurs, des fractures pathologiques, une hypercalcémie, une compression médullaire et une augmentation de la mortalité. Leur prise en charge nécessite une approche multidisciplinaire. Elle comporte l’association du traitement antitumoral à un traitement inhibiteur de la résorption, et si nécessaire à un traitement local des atteintes osseuses. Les bisphosphonates sont recommandés pour diminuer les complications de ces lésions osseuses. La radiothérapie ou la chirurgie peuvent être nécessaires en cas de douleur mal contrôlée, de fractures pathologiques ou de compression médullaire. Une vertébroplastie ou une cyphoplastie peuvent être envisagées en cas de fractures vertébrales symptomatiques. D’autres traitements ciblant notamment dickkopf-1, activin-A ou BAFF sont en cours d’étude.
Recent advances in the treatment of multiple myeloma have resulted in improved prognosis, but bone lesions remain a major concern in these patients. Multiple myeloma bone disease is characterized by increased bone resorption and decreased bone formation. Myeloma bone lesions are osteolytic and are often associated with pain, pathologic fractures, hypercalcemia, spinal cord compression and increased mortality. A multidisciplinary approach is needed to manage multiple myeloma bone lesions. Current management of multiple myeloma bone disease involves the combination of anti-myeloma therapy, anti-resorptive therapy, and if necessary a local treatment of skeletal lesions. Bisphosphonates are the current standard of care for reduction in skeletal-related events. Radiotherapy or surgery can be used for specific conditions such as uncontrolled pain, pathologic fractures or spinal cord compression. Vertebroplasty or kyphoplasty should be considered in case of symptomatic vertebral fractures. Other treatments targeting dickkopf-1, activin-A, and BAFF are under development.
New treatments for myeloma Azaïs, Isabelle; Brault, Rachel; Debiais, Françoise
Joint, bone, spine : revue du rhumatisme,
01/2010, Letnik:
77, Številka:
1
Journal Article
Recenzirano
Abstract The management of multiple myeloma has benefited substantially from the introduction of three new drugs, namely, the proteasome inhibitor bortezomib and the immunomodulators thalidomide and ...lenalidomide. These drugs were initially shown to improve the outcome of advanced myeloma and were subsequently found to transform the treatment of patients with previously untreated myeloma. Melphalan and prednisone combined with thalidomide or bortezomib is the new treatment of reference for patients who are elderly or ineligible for intensification. The introduction of these new drugs into induction regimens, intensified conditioning regimens, and posttransplantation regimens may improve overall survival among young patients by increasing the rate and quality of the treatment responses. Although myeloma remains incurable, prolonged survival is now a reasonable objective.
Présenter le devenir de 15 grossesses chez des femmes exposées aux agents anti-TNF au moment de la conception ou pendant leur grossesse.
Il était demandé aux rhumatologues français qui se ...connectaient sur le site web du CRI (http://www.cri-net.com) de remplir un questionnaire préétabli présentant les résultats des grossesses des patientes traitées par agents bloquants du TNF au moment de la conception.
Huit femmes atteintes de spondylarthropathies, quatre de polyarthrites rhumatoïdes, deux d’arthrites juvéniles idiopathiques et une d’un rhumatisme psoriasique ont été traitées par infliximab (n=3), adalimumab (n=2) ou étanercept (n=10). Deux fausses couches sont survenues et une interruption volontaire de grossesse a été préférée. Les agents anti-TNF ont été administrés pendant le premier, le deuxième et le troisième trimestre de la grossesse, respectivement chez 12, trois et deux patientes. Les 12 nouveaux-nés étaient en bonne santé, sans malformation apparente, ni symptômes de maladie néonatale.
Le nombre de cas rapportés dépasse les 300, mais seulement 29 femmes ont été traitées pendant la totalité de leur grossesse. Le taux de malformations congénitales observées jusqu’à présent peut apparaître rassurant en comparaison à celui de la population générale des femmes exposées seulement pendant la conception. Inversement, il y a trop peu de cas rapportés d’exposition pendant la grossesse pour conclure sur la sécurité d’utilisation des agents bloquants du TNF. Un suivi supplémentaire à long terme de ces enfants permettrait d’exclure les formes mineures d’association VACTERL® qui peuvent être passées inaperçues à la naissance.
Nouvelles thérapies du myélome Azaïs, Isabelle; Brault, Rachel; Debiais, Françoise
Revue du rhumatisme (Ed. française : 1993),
January 2010, 2010, 2010-01-00, Letnik:
77, Številka:
1
Journal Article
L’apparition de nouveaux agents tels que l’inhibiteur du protéasome bortézomib et les immunomodulateurs thalidomide et lénalidomide constitue un réel progrès dans la prise en charge du myélome. Après ...avoir considérablement amélioré le pronostic du myélome en phase avancée, ils ont radicalement transformé le traitement initial de cette affection : les associations melphalan-prednisone-thalidomide et melphalan-prednisone-bortézomib sont devenus les nouveaux traitements de référence des sujets âgés ou non éligibles pour une intensification ; l’introduction de ces agents dans le traitement d’induction, le conditionnement de l’intensification et le traitement postgreffe laisse espérer une amélioration de la survie globale des sujets jeunes en augmentant le taux et la qualité des réponses obtenues. Si la guérison du myélome reste encore illusoire, il devient possible de vivre longtemps avec cette hémopathie.
