CASTOR combination is promising treatment for multiple myeloma
The addition of daratumumab to bortezomib and dexamethasone significantly prolonged PFS and time to progression in patients with relapsed or refractory multiple myeloma, according to early results of the CASTOR study presented during the plenary session of the ASCO Annual Meeting. The combination with daratumumab also doubled the rates of very good partial and complete response and demonstrated a safety profile consistent with the known toxicity profiles of the agents. HemOnc Today invited Ruben Niesvizky, M.D., director of the Weill Cornell Myeloma Center, to give his perspective of the study. Read the full article here.
Ruben Niesvizky, M.D.
Daratumumab (Darzalex, Janssen) is a human IgG1k monoclonal antibody directed against the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through programmed cell death — or apoptosis — and multiple immune-mediated mechanisms, including complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.
The U.S. approval of daratumumab for patients with multiple myeloma who have received at least three prior lines of therapy — including a proteasome inhibitor and an immunomodulatory agent — or who are double refractory to a proteasome inhibitor and an immunomodulatory agent came about after the results of phase 2 single-agent data were reported. Indeed, the study using daratumumab at 16 mg/kg showed in this very ill population a 29.2% response rate and a median duration of response of 7.4 months.
The recent report at ASCO determined the PFS of the combination of the three-drug regimen of daratumumab plus bortezomib and dexamethasone compared with the control regimen, which consisted of bortezomib and dexamethasone alone. As expected, the three-drug combination performed much better, and the fact the results showed a 61% decreased risk for progression or death is staggering. We are very eager to see follow-up of long-term, more mature results that might inform us if this signal is sustained. Nevertheless, this is enough argument to move the drug earlier in the course of patients, and hopefully it will be incorporated earlier in first line. We still have to learn to discern which patients will benefit from this drug, the effect on stem cell viability and collection, and long-term benefit.