A phase 3 trial reports that a combined regimen of subcutaneous bortezomib, lenalidomide, and dexamethasone (VRD) is effective as induction therapy prior to autologous stem cell transplant (autoSCT) in newly diagnosed multiple myeloma, with responses that strengthen over time.
"Achieving and maintaining high-quality response is the treatment goal for patients with newly diagnosed multiple myeloma," state the researchers in their publication in Blood, led by first author Laura Rosiñol, MD, PhD, a hematologist at the Hospital Clinic of the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) of the University of Barcelona, Spain. "VRD is an effective and well-tolerated regimen for induction in [newly diagnosed multiple myeloma], with deepening response throughout induction and over the course of treatment."
The PETHEMA/GEM2012 study (NCT01916252) is evaluating the efficacy of VRD followed by autoSCT in 458 patients age 65 or younger with newly diagnosed multiple myeloma. Patients were administered VRD for six cycles, followed by autoSCT conditioned with intravenous busulfan/melphalan versus melphalan alone, followed by posttransplant consolidation consisting of two additional cycles of VRD.
Of the 426 patients who initiated the sixth induction cycle, 55.6% achieved at least a very good partial response by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% following induction. The VRD regimen produced a complete response rate of 33.4% after induction in the intent-to-treat population; this response deepened to 44.1% following autoSCT and to 50.2% following consolidation. Similarly, rates of undetectable minimal residual disease increased in the intent-to-treat population, with rates of 28.8% following induction rising to 42.1% following transplant and to 45.2% following consolidation.
Neutropenia was the most frequent grade 3 or higher treatment-emergent adverse event during induction therapy, experienced by 12.9% of patients, with the second most frequent being infection, experienced by 9.2% of patients. Peripheral neuropathy of grade 2 or higher affected 17.0% of patients, with a low occurrence of grade 3 and 4 events (3.7% and 0.2%, respectively).
"VRD was highly effective and well tolerated before autoSCT," conclude Dr. Rosiñol and colleagues. "Responses deepened with VRD throughout induction and over the course of treatment, with few discontinuations due to toxicity."
For More Information
Rosiñol L, Oriol A, Rios R, et al (2019). Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplantation in multiple myeloma. Blood. [Epub ahead of print] DOI:10.1182/blood.2019000241
Image credit: Michaela Reagan, Maine Medical Center Research Institute. Courtesy of the National Cancer Institute / Dana-Farber Harvard Cancer Center