Sequencing Novel Agents in Relapsed/Refractory Multiple Myeloma: Use of Bortezomib-Based Therapy After Lenalidomide + Dexamethasone.
Notice bibliographique
Résumé
Abstract Abstract 1853 Poster Board I-879 The optimal sequencing of novel agents in multiple myeloma (MM) is not certain. In Ontario, we had a unique opportunity to assess the efficacy of bortezomib (btz) in patients (pts) with MM who progressed after preferential treatment with lenalidomide + dexamethasone (len+dex) given via access programs/clinical trials for relapsed/refractory (rel/ref) disease. These pts all received len+dex, followed by btz-based regimens for their next relapse without any interim therapy. Between 12/2005 and 5/2009, 49 MM pts received len+dex for recurrent MM (23 in first, 20 in second, 5 in third, and 1 in fourth relapse after primary therapy). Thirty-nine pts (80%) had previously undergone autologous stem cell transplantation as part of initial therapy. Median age was 56 (range 31-77) yrs; 27 (55%) were male. The immunoglobulin subtype included IgG (21), IgA (15), IgM (1), light chain only (11) and non-secretory MM (1). ISS myeloma stage at referral consisted of stage 1 in 25 (50%), stage 2 in 18 (37%), stage 3 in 8 (16%), and not evaluable in 2 (4%) . Median β2-microglobulin level was 257 nmol/L, creatinine 77 umol/L and albumin 39 g/L. FISH cytogenetics, available in 19 pts, showed 13q del in 7, t(4;14) in 3 and p53 del in 3 pts. The median treatment duration of len+dex was 5.3 (0.5-47.5) mos; best clinical response included nCR in 3 (6%), VGPR in 3 (6%), PR in 25 (51%), MR in 6 (12%), SD in 6 (12%) and progressive disease (PD) in 6 (12%). Subsequent btz-based therapy included btz alone in 20 (41%), btz + corticosteroids (CS) in 23 (47%), btz + CS + p.o. cyclophosphamide in 4 (8%), and btz + other drug(s) in 2 (4%) of the pts. The median duration of btz-based therapy was 3.0 (0.5-17.2) mos. The best clinical response to btz-based therapy was nCR in 1 (2%), VGPR in 8 (16%), PR in 12 (25%), MR in 7 (14%), SD in 9 (18%) and PD in 12 (25%). The median follow-up from the start of btz-based therapy was 6.5 (1-29.5) mos. The median PFS and OS were 5.6 (95% CI 3.7-8.6) mos and 10.8 (95% CI 5.3-11.8) mos, while the 1-yr progression-free survival (PFS) was 20% (95% CI 9-35%) and overall survival (OS) 33% (95% CI 17-49%) mos, respectively, from the start of btz. Assessment of prognostic factors such as age at diagnosis, gender, myeloma subtype, duration from initial therapy to first relapse, previous response to len+dex, and type of btz-based therapy did not reveal a correlation with PFS or OS. However, achievement of ≥ PR with btz correlated with PFS (p=0.05) and OS (p=0.004). We conclude that treatment of sequential MM relapses with btz-based therapy after progression on len+dex: 1) produces ≥ PR in 43%; 2) results in a median PFS similar to the 6.22 mos seen with btz in less heavily pretreated pts in the APEX trial (Richardson P, et al. New Engl J Med 2005; 352:24); 3) demonstrates the effectiveness of btz even after exposure to the potent len+dex combination; 4) provides baseline information for evaluating the relative efficacy of the sequential versus combination use of novel agents in rel/ref MM. Disclosures: Reece: Ortho Biotech: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau. Chen:Celgene: Honoraria, Research Funding; Ortho Biotech: Honoraria. Kukreti:Celgene: Honoraria. Anglin:Celgene: Honoraria. Trudel:Ortho Biotech: Honoraria, Research Funding; Celgene: Honoraria.
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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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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) | 0,001 | 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 ».