Newly Diagnosed Myeloma (MM) Patients (Pts) with High-Risk (HR) Cytogenetics By FISH: Is There a Role for Tandem Autologous Stem Cell Transplantation (ASCT)?
Notice bibliographique
Résumé
Abstract Background: Recent analyses have suggested that newly diagnosed multiple myeloma (MM) patients with the high-risk (HR) chromosomal abnormalities del 17p and t(4;14) detected by FISH may benefit from bortezomib (BTZ)-based induction therapy and tandem autologous stem cell transplantation (ASCT) (Sonneveld P et al, J Clin Oncol 2013;31: 3279). At Princess Margaret Cancer Centre, we have offered upfront tandem ASCT for HR pts with del 17p, t(4;14) and/or t(14;16) and now retrospectively review the results of this approach. Methods: After obtaining Institutional Research Ethics Board approval, we used Princess Margaret Myeloma Database to identify HR MM pts who underwent tandem ASCT between June 2005 and January 2015. We performed a retrospective chart review to investigate the survival outcome of this group of patients. Results: Between 06/05 and 01/15, 52 HR pts underwent tandem ASCT at Princess Margaret Cancer Centre. 21 had del 17p, 20 had t(4;14), 5 had t(14;16), 3 had both t(4;14) + del 17p and 3 had both t(14;16) + del 17p. Median age was 56.5 yrs (range 31-71); 34 were male. ISS stage was I in 12, II in 15, III in 12 and N/A in 13 pts. The majority (42 pts) received BTZ-based induction therapy which consisted of CyBorD in 38; 11 pts required a 2nd regimen before ASCT. The median time from diagnosis to 1st ASCT was 6.7 mos (range 4.8 -45.7) and the median time between transplants was 3.7 mos (range 0.9- 6.6); 30 pts received lenalidomide (len) between ASCTs to prevent early relapse. All but 2 pts (96%) received maintenance therapy after the 2nd ASCT which included thalidomide in 7 (13%), len +/- steroids in 39 (75%) and BTZ +/- len in 4 (8%) of all pts. Thirty-six (69%) received both BTZ-based induction and len maintenance after the 2nd ASCT. No transplant-related deaths occurred. Median follow-up is 26.3 mos (range 9.1 to 104.3). The median overall survival in all 52 pts from diagnosis was 31.1 mos (range 11.9 to 110.8) with a median PFS of 24.0 mos (9.1 to 83.6); median survival after progression was only 8.2 mos (0.1-62.8) mos in the 16 pts who relapsed after the 2nd ASCT.Table 1.HR Group#Calculated from diagnosisCalculated from 2nd ASCTMedian PFS, mos (range)Median OS, mos (range)Median PFS, mos (range)Median OS, mos (range)t(4;14)2322.4 (11.4-58.1)29.9 (17.7-84.4)7.0 (0.2-23.5)17.3 (5.4-73.6)Del 17p2724.4 (9.1-83.6)35.0 (11.9-110.8)11.2 (1.3-69.4)25.3 (3.8-99.6)t(14;16)827.4 (10.3-55.4)30.6 (11.9-55.4)16.9 (2.2-48.1)19.7 (3.8-48.1)Both BTZ-induction + len maint3622.2 (10.3-55.4)30.5 (11.9-67.5)8.1 (1.4-48.1)18.7 (3.8-57)No BTZ-induction + len maint1627.2 (9.1-83.6)49.5 (22.0-110.8)12.1 (0.2-69.4)24.5 (6.9-99.6) Conclusions: 1) MM pts with HR cytogenetics, particularly those with t(4;14), have a short PFS and OS after tandem ASCT; 2) even following BTZ-based induction therapy and len maintenance, outcomes with tandem ASCT are suboptimal in HR pts; 3) further investigations are necessary to identify novel strategies for the management of HR MM in the era of modern therapeutic agents. Disclosures Chen: Celgene: Consultancy, Honoraria, Research Funding. Kukreti:Janssen Ortho: Honoraria; Roche: Honoraria; Lundbeck: Honoraria; Amgen: Honoraria; Celgene: Honoraria. Tiedemann:Janssen Ortho: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Trudel:Oncoethix: Research Funding; Novartis: Honoraria; Trillium Therapeutics Inc.: Research Funding; BMS: Honoraria; Amgen: Honoraria, Speakers Bureau; Celgene: Equity Ownership, Honoraria, Speakers Bureau. Reece:Lundbeck: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Otsuka: Research Funding; Merck: Research Funding; Millennium Takeda: Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Honoraria; Onyx: Consultancy; Janssen-Cilag: Consultancy, Honoraria, Research Funding.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».