Prospective Canadian Trial In Newly Diagnosed Multiple Myeloma Patients with t(4;14): Bortezomib-Based Therapy without ASCT
Notice bibliographique
Résumé
Abstract Abstract 1968 Two previous studies have reported that multiple myeloma (MM) patients (pts) with t(4;14), identified by FISH cytogenetics, experience a median progression-free survival (PFS) of only 8–9 mos and median overall survival (OS) of 18 mos when treated with a single ASCT (Chang H, et al. Bone Marrow Transplant 2005; 36: 793; Gertz M, et al. Blood 2005; 106: 2837). On the other hand, the novel agent bortezomib is efficacious in relapsed myeloma pts with t(4;14). Based on these observations, we designed a phase II protocol for newly diagnosed MM pts with t(4;14) that consists of induction with pegylated liposomal doxorubicin, bortezomib and dexamethasone (DBD) × 4 cycles, followed by post-induction therapy with oral cyclophosphamide 300 mg/m2 days 1,8 15, 22 with bortezomib 1.5 mg/m2 days 1,8,15 and prednisone 100 mg q 2 days of a 28-day cycle (CyBor-P) × 8 additional cycles. Maintenance therapy with dexamethasone (dex) 40 mg/month was then administered until progression. Although elective stem cell collection was recommended after induction, routine ASCT was not performed in the absence of disease progression. Between February 2008-July 2010, the bone marrows of 201 newly diagnosed MM pts were screened for t(4;14) in 7 Canadian centers, and 31 (15.4%) were found to be positive by FISH. Five pts did not meet the criteria for symptomatic MM, 4 had received ≥ 2 mos of prior therapy, 1 refused treatment and 2 were ineligible due to peripheral neuropathy or renal failure. Nineteen pts have been entered onto study. One of these was later determined to have a variant abnormality of chromosome 4 but not t(4;14) and underwent ASCT after induction; this pt is included in the safety analysis only. The median age was 60 yrs (45-69) and 53% were male. The median percent nuclei positive for t(4;14) was 26% (3-44%), serum β2-microglobulin was 318 nmol/L (43-1695) and albumin was 36 g/L (28-48); 6 pts had ISS stage 1, 6 had stage 2 and 5 had stage 3 MM. Immunoglobulin subtype included IgGκ (5), IgGλ (4), IgAκ (3), IgAλ (4), λ LC (1) and nonsecretory (1). To date, 15 pts have commenced DBD induction (57 total cycles administered), 12 have started post-induction CyBor-P (67 total cycles) and 6 are on maintenance dex (35 total cycles). Using modified Uniform criteria, the best response in 15 evaluable pts includes: sCR in 3 (20%), CR in 3 (20%), VGPR in 6 (40%), PR in 1 (6.7%) and stable disease in 2 (13.3%). Four have progressed a median of 3 mos (1-11) after commencing induction; one who progressed through DBD remains in nCR 1.5 yrs after salvage D-PACE followed by ASCT and lenalidomide maintenance. Fourteen SAEs occurred, of which 11 were grade 3 and 0 were grade 4; 5 pts developed grade 2 peripheral neuropathy (numbness and tingling) during induction with DBD. Grade 3/4 neutropenia was seen in 2/0 pts, and grade 3/4 thrombocytopenia in 2/1 pts, respectively. Two pts have died, due to MM progression in 1 and complex medical problems including syringomyelia with progressive weakness/ruptured diverticuli/depression in another who withdrew consent despite achieving VGPR with induction. Median follow-up (F/U) is 9.4 mos (1-23). Actuarial PFS is 66% (95% CI 42–100%) and overall survival is 92% (95%CI 79–100%) at 1 year. We conclude: 1) the incidence of t(4;14) by FISH in newly diagnosed MM pts is 15.4% as expected; 2) 26% of newly diagnosed pts with this entity have asymptomatic MM; 3) this bortezomib-based regimen is well-tolerated; 4) the overall response rate (sCR + CR + VGPR + PR) is 87%; 5) preliminarily, the 1-year PFS and OS with this approach compare favorably with reports of single ASCT in t(4;14) positive MM, although longer follow-up is required. Disclosures: Reece: Ortho Biotech: Honoraria, Research Funding. Off Label Use: Bortezomib as first line therapy in myeloma. Chen:Ortho Biotech: Honoraria. Kukreti:Ortho Biotech: Honoraria. Anglin:Ortho Biotech: Honoraria. Trudel:Ortho Biotech: Honoraria.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,001 |
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 ».