In an analysis reported in the Journal of Clinical Oncology, Martin F. Kaiser, MD, and colleagues found that daratumumab plus low-dose cyclophosphamide, lenalidomide, bortezomib, and dexamethasone (Dara-CVRd) used as induction and extended consolidation therapy in newly diagnosed patients with ultra–high-risk multiple myeloma or plasma cell leukemia in the OPTIMUM trial produced better progression-free survival outcomes vs standard treatment used in ultra–high-risk patients in the recent Myeloma XI (MyeXI) trial.
Study Details
In the OPTIMUM trial, transplant-eligible patients were profiled for ultra–high-risk disease, defined as the presence of at least two of the genetic risk markers t(4;14)/t(14;16)/t(14;20), del(1p), gain(1q), and del(17p) or SKY92 gene-expression risk signature. Patients with ultra–high-risk multiple myeloma or plasma cell leukemia were offered treatment with Dara-CVRd induction, V-augmented autologous stem cell transplantation (ASCT), extended Dara-VR(d) consolidation, and Dara-R maintenance.
Martin F. Kaiser, MD
Ultra–high-risk patients treated in the MyeXI trial with carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide; or lenalidomide, dexamethasone, and cyclophosphamide, ASCT, and R maintenance; or observation were identified by molecular screening. Progression-free survival at 18 months in the OPTIMUM vs MyeXI ultra–high-risk groups was compared using a Bayesian model.
Key Findings
The ultra–high-risk groups consisted of 103 patients from the OPTIMUM trial and 117 patients from the MyeXI trial. Comparison of 18-month progression-free survival using the Bayesian model showed a 99.5% chance that the OPTIMUM regimen was superior to MyeXI treatment. The rate at 18 months was 81.7% vs 65.9%.
At 30 months, progression-free survival rate was 77.0% (95% confidence interval [CI] = 68.8%–85.1%) in the OPTIMUM group vs 39.8% (95% CI = 30.7%–48.9%) in the MyeXI group. Median overall survival rate was 83.5% (95% CI = 76.4%–90.7%) vs 73.5% (95% CI = 65.5%–81.5%).
As stated by the investigators: “Extended post-ASCT Dara-VRd consolidation therapy was highly deliverable, with limited toxicity.”
The investigators concluded: “Our results suggest that Dara-CVRd induction and extended post-ASCT Dara-VRd consolidation markedly improve progression-free survival for ultra–high-risk newly diagnosed [patients with multiple myeloma] over conventional management, supporting further evaluation of this strategy.”
Dr. Kaiser, of the Myeloma Molecular Therapy Team, The Institute of Cancer Research, London, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was funded by Myeloma UK, David Forbes Nixon Foundation, Celgene, and Janssen. For full disclosures of the study authors, visit ascopubs.org.
