Phase 3 randomised study of daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): CASTOR

Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma

This phase 1/2 study was the first to evaluate the safety and efficacy of the cyclin-dependent kinase (CDK) 4/6-specific inhibitor palbociclib (PD-0332991) in sequential combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. The recommended phase 2 dose was palbociclib 100 mg orally once daily on days 1-12 of a 21-day cycle with bortezomib 1.0 mg/m2 (intravenous) and dexamethasone 20 mg (orally 30 min pre-bortezomib dosing) on days 8 and 11 (early G1 arrest) and days 15 and 18 (cell cycle resumed). Dose-limiting toxicities were primarily cytopenias; most other treatment-related adverse events were grade≤3. At a bortezomib dose lower than that in other combina…

Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma.

Daratumumab, a human IgGκ monoclonal antibody that targets CD38, induces direct and indirect antimyeloma activity and has shown substantial efficacy as monotherapy in heavily pretreated patients with multiple myeloma, as well as in combination with bortezomib in patients with newly diagnosed multiple myeloma.In this phase 3 trial, we randomly assigned 498 patients with relapsed or relapsed and refractory multiple myeloma to receive bortezomib (1.3 mg per square meter of body-surface area) and dexamethasone (20 mg) alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratumumab group). The primary end point was progression-free survival.A prespecifie…

Efficacy and safety of daratumumab, bortezomib, and dexamethasone (D-Vd) in relapsed or refractory multiple myeloma (RRMM) based on cytogenetic risk: Updated subgroup analysis of CASTOR.

8040 Background: MM patients (pts) with high cytogenetic risk have poor outcomes. In CASTOR, D-Vd prolonged progression-free survival (PFS) vs bortezomib and dexamethasone (Vd) alone, and exhibited tolerability in RRMM pts. We conducted a subgroup analysis of D-Vd vs Vd in CASTOR, based on cytogenetic risk. Methods: Pts received ≥1 prior line of therapy. Cytogenetic risk was based on a combined analysis of next-generation sequencing (NGS) and fluorescence in situ hybridization/karyotype testing. High-risk pts had t(4;14), t(14;16), or del17p abnormalities. Standard (std)-risk pts were confirmed negative for all 3 abnormalities. Minimal residual disease (MRD; 10–5) was assessed via NGS usin…

Health-related quality of life maintained over time in patients with relapsed or refractory multiple myeloma treated with daratumumab in combination with bortezomib and dexamethasone: results from the phase III CASTOR trial.

In the phase III CASTOR trial, daratumumab, bortezomib and dexamethasone (D-Vd) significantly extended progression-free survival compared with bortezomib and dexamethasone (Vd) alone in patients with relapsed/refractory multiple myeloma (RRMM). Here, we present patient-reported outcomes (PROs) from the CASTOR trial. PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system questionnaire. Treatment effects through Cycle 8 were measured by a repeated measures mixed-effects model. After Cycle 8, PROs were only collected for patients in the D-Vd group who con…