|The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
The phase 3 CASSIOPEIA trial (ClinicalTrials.gov Identifier: NCT02541383) met its primary end point of improvement in the rate of stringent complete response (sCR) for patients with transplant-eligible, newly-diagnosed multiple myeloma receiving daratumumab in addition to a regimen of bortezomib/thalidomide/dexamethasone (DVTd) vs VTd alone. The findings of this study were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.1
Daratumumab is a monoclonal antibody that targets CD38, a glycoprotein expressed on the surface of different types of cells, including malignant plasma cells in multiple myeloma and many types of immune cells. It is believed to inhibit the growth of multiple myeloma cells through induction of antibody-dependent cell-mediated toxicity, and immune-mediated cell lysis, as well as other mechanisms of action.3
While the benefit of daratumumab has been previously demonstrated, as either monotherapy or in combination with standard-of-care regimens for patients with relapsed/refractory multiple myeloma, or when combined with bortezomib/melphalan/dexamethasone for transplant-ineligible, newly diagnosed patients with multiple myeloma—resulting in approval by the US Food and Drug Administration (FDA) for these indications3 — part 1 of the large, open-label, randomized, phase 3 CASSIOPEIA study evaluated the efficacy and safety of adding daratumumab to VTd in the treatment of patients with transplant-eligible newly diagnosed multiple myeloma who were aged 65 years or older. The primary end point of the study was postconsolidation sCR (ie, complete response [CR] plus criteria including normal serum-free light chain ratio, and less than 5% plasma cells in bone marrow) as assessed 100 days following autologous stem cell transplantation (ASCT).
Specifically, in part 1 of the multicenter, open-label CASSIOPEIA study, 1085 patients were randomly assigned in a 1:1 ratio to receive VTd as induction therapy (4 cycles) and post-ASCT consolidation therapy (2 cycles) with and without daratumumab administered at an intravenous (IV) dose of 16 mg/kg every week for cycles 1 and 2 and every 2 weeks for cycles 3 through 6. Following consolidation, patients eligible to receive maintenance therapy were re-randomized (1:1) to receive daratumumab monotherapy or observation alone.
Baseline characteristics of the study population included a median age of approximately 59 years and high-risk disease in approximately 15% of patients. At a median follow-up of 18 months, approximately 90% of patients in each study arm underwent ASCT.
Key findings from the study included significant improvement in the sCR rate with addition of daratumumab (29% vs 20%; odds ratio (OR), 1.60; 95% CI, 1.21-2.12; P =.0010) following consolidation therapy.
“For sCR, DVTd was superior to VTd across all prespecified subgroups except high-risk cytogenetics and Revised International Staging System (RISS) III,” commented Dr Moreau, the presenter of the study results.
In addition, the respective rates of minimal residual disease negativity (MRD)-negativity (10-5 sensitivity) following consolidation were 64% (DVTd) vs 44% (VTd; P <.0001), and this daratumumab-related benefit was observed across all different disease risk subgroups.
Furthermore, at a median follow-up of 18 months, progression-free survival (PFS) from first randomization was significantly longer for patients receiving daratumumab. Although median PFS was not reached in either study arm, rates of PFS at 18 months (when very few patients had received maintenance therapy) were 93% and 85% for patients receiving daratumumab vs not (HR, 0.47; 95% CI, 0.33-0.67; P <.0001), and this benefit of daratumumab was also observed across all pre-specified subgroups. Data on overall survival (OS), another secondary end point of the study, are still immature.
Regarding safety, the most common grade 3 or 4 treatment-emergent adverse events were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), stomatitis (13% vs 16%), and thrombocytopenia (11% vs 7%) for those treated with and without daratumumab, respectively. Interestingly, the rate of grade 3 or 4 infections was similar in the 2 study arms (22% [DVTd] and 20% [VTd]). For patients in the daratumumab arm, 35% experienced infusion-related reactions.
In his closing comments, Philippe Moreau, MD, University Hospital Hôtel-Dieu, Nantes, France, noted “that DVTd should be considered a valid treatment option for newly diagnosed patients with multiple myeloma who are eligible for ASCT.”
Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.
- Moreau P, Attal M, Hulin C, et al. Phase 3 randomized study of daratumumab (DARA) + bortezomib/thalidomide/dexamethasone (D-VTd) vs VTd in transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 1 results. Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 8003.
- Daratumumab (Darzalex®) [package insert]. Horsham, PA: Janssen Biotech, Inc.; 2018.