Pomalidomide-Containing Regimens (PCR) for the Treatment of Relapsed and Refractory Multiple Myeloma
Notice bibliographique
Résumé
Abstract Introduction: Pomalidomide is an IMiD that was recently approved for the use of relapsed MM failing lenalidomide and bortezomib. In the present study, we aimed to evaluate the efficacy of pomalidomide-containing regimens (PCR) for heavily-pretreated relapsed or refractory MM (RRMM) at Tom Baker Cancer Center and the Cross Cancer Institute in Alberta. Methods: We retrospectively reviewed the records of all patients with RRMM treated with PCR at our Institutions between 01/10 and 04/15. Patients received oral pomalidomide 2-4mg/d on days 1-21/28, and dexamethasone 20 mg or 40 mg on a weekly schedule, few cases were treated with PD in addition to bortezomib or cyclophosphamide. Definitions of response and progression were used according to the EBMT modified criteria. A p-value was considered statistically significant if <0.05 Results: Between 01/10 and 04/15, 90 patients were identified for the study. Clinical and laboratory characteristics are listed in Table 1. The median number of therapies prior to PCR was 3 (2-11). All patients received lenalidomide and bortezomib or another proteasome inhibitor prior to PCR; 47 patients had bortezomib, 31 had lenalidomide and 11 had both immediately prior to PCR. 21 patients out of 47 receiving bortezomib prior to PCR responded (44%) versus 32.2% (10/31), and 27.2% (3/11), for those receiving lenalidomide and lenalidomide/bortezomib, respectively prior to PCR (p=0.5). Four patients received pomalidomide at a dose of 2mg, 3 at 3mg and the rest at 4mg. After a median of 4 cycles, the ORR was 41.1%. The median time to first response was 8 weeks, with majority of cases achieving at least PR after 2 cycles. FISH cytogenetics at relapse, were available in 46 patients and 16 were high risk (HR, 34.8%). At a median follow-up of 8 months, 44% of patients were alive and 77.8% had already progressed. Median OS was 12.2 months and median PFS 4.0 months. Median PFS was 5.6 months in the group with standard risk (SR) disease compared to 2.9 months for the HR group (p=0.022). Median OS for SR patients was 19.4 months compared to 8 months for the HR group (p=0.11). Two patients discontinued therapy due to thrombocytopenia. Conclusion: Pomalidomide is an efficacious drug for the treatment of RRMM. The current report confirms the ORR seen in previous studies and suggests a trend to poorer outcomes for the HR cytogenetics group. Further assessment of combinations of pomalidomide with newer agents especially in the setting of HR cytogenetics are warranted. Table 1. Clinical Characteristics and Response assessment for patients with MM receiving pomalidomide-containing regimens Characteristic N=90 Age (median) 65 GenderMaleFemale 46 (51.1%)44 (48.9%) Hb (g/L) 108 (75-160) Calcium (µmol/L) 2.3 (1.98-3.28) Creatinine (µmol/L) 85.5 (60-1052) B2microglobulin (µmol/L) 3.96 (1.38-25.2) Albumin (g/L) 35.5 (11-52) Stage IStage IIStage III 15.9%52.3%31.8% LDH (IU/L) 190 (71-669) BMPC (%) 40% (5-90%) Heavy chain:IgGIgAIgDBiclonalIgMFLC onclyNon-secretory 61.1%20%01.1%5.6%10%2.2% Light chain:KappaLambda 64.4%33.3% Prior therapies:ASCTThalidomideLenalidomideBortezomibCarfilzomib 53.3%21.1%100%98.9%8.9% High risk (t(4;14), t(14;16), and p53 delStandard risk 34.8%65.2% Chemotherapy regimenDPPACEPomalidomide alonePomalidomide and DexamethasonePomalidomide/Bortezomib and DexamethasonePomalidomide and BortezomibPomalidomide, cyclophosphamide and prednisone 1.1%1.1%88.9%6.7%1.1%1.1% Response rateORRComplete Response/nCRVGPRPRSDMinimal ResponseProgression 41.1%2.2%5.6%33.3%18.9%10%30% Patients that have progressed 77.8% Patients that have died 55.6% BMPC: Bone marrow plasma cells; FLC: Free-light chains only; CC: Conventional cytogenetics Figure 1. Progression-Free survival according to high-risk cytogenetics by FISH Figure 1. Progression-Free survival according to high-risk cytogenetics by FISH Disclosures Jimenez-Zepeda: J&J: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Venner:Amgen: Honoraria; J&J: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Sandhu:Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Neri:Celgene: Research Funding. Bahlis:Johnson & Johnson: Research Funding; Amgen: Consultancy; Johnson & Johnson: Consultancy; Johnson & Johnson: Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.
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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 | 0,000 | 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 ».