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Treatment with the combination of bortezomib (Velcade), mitoxantrone hydrochloride liposome (Lipo‐MIT), and dexamethasone (VMitD) led to responses and displayed a manageable safety profile in patients with relapsed/refractory multiple myeloma, according to data from a phase 1 trial (NCT05052970).
Findings published in Cancer Medicine demonstrated that evaluable patients (n = 15) experienced an overall response rate (ORR) of 86.7%, which comprised complete response (CR) or stringent CR (sCR; n = 3); very good partial response (VGPR; n = 6); PR (n = 4); and minor remission (n = 1). One patient experienced stable disease. The 12-month duration of response (DOR) rate was 66.0% (95% CI, 23.92%-88.63%).
Regarding safety, hematologic and non‐hematologic adverse effects (AEs) were common, but the vast majority were mild to moderate. Treatment‐related AEs (TRAEs) did not lead to deaths in any patients. The only common grade 3/4 non-hematologic AE was infectious pneumonia, which occurred in 20% of patients (n = 20). Common grade 3/4 hematologic AEs included thrombocytopenia (70%), neutropenia (55%), lymphopenia (30%), and anemia (10%).
“This trial is the first to present outcomes using a triplet regimen including Lipo‐MIT for relapsed/refractory multiple myeloma, demonstrating good tolerance and promising efficacy,” lead study author Ya‐Lan Zhou, MD, of Department of Hematology at Beijing Chaoyang Hospital of Capital Medical University in China, and colleagues wrote in the publication. “However, further studies are required to more accurately assess patient outcomes, and in‐depth mechanistic studies are needed to identify potential biomarkers that could predict response to this regimen.”
Why Was Lipo‐MIT Evaluated for Relapsed/Refractory Multiple Myeloma?
In China, Lipo-MIT is currently approved for the treatment of patients with relapsed/refractory peripheral T‐cell lymphoma. Given the superior efficacy displayed by Lipo-MIT compared with conventional anthracyclines, investigators sought to evaluate the use of this agent as part of a combination regimen for patients with relapsed/refractory multiple myeloma.
The multicenter, open‐label, phase 1 study enrolled patients at least 18 years of age with relapsed/refractory multiple myeloma who had measurable disease and received at least 1 prior line of treatment. Prior treatment with bortezomib was permitted if patients were not resistant or intolerant to the agent.
Investigators excluded patients with compromised hematologic reserve, liver dysfunction, or diminished performance status. Those in need of hemodialysis were also excluded. Other key exclusion criteria included a history of plasma cell leukemia, HIV, or active hepatitis.
Patients were randomly assigned 1:1:1 to receive varying doses of Lipo-MIT as part of the VMitD regimen. LipoMIT was dosed at 12 mg/m2 on day 1 of each 4-week cycle in cohort A, 16 mg/m2 in cohort B, and 20 mg/m2 in cohort C. In all 3 cohorts, patients received bortezomib at 1.3 mg/m2 on days 1, 4, 8, and 11 of each cycle plus dexamethasone at 20 mg on days 1, 2, 4, 5, 8, 9, 11, and 12 of each cycle. Eight cycles of treatment were planned for each cohort.
The incidence of treatment-emergent AEs served as the trial’s primary end point. Secondary end points comprised ORR, DOR, clinical benefit rate, disease control rate, progression-free survival (PFS), and overall survival.
Among the overall population (n = 20), the median age was 61.5 years (range, 42-70), and most patients were male (60%), had IgG myeloma (55.0%), and did not have extramedullary plasmacytomas (80%). Patients received a median of 2.5 prior lines of therapy (range, 1-8), and patients had either relapsed (90%) or refractory (10%) disease.
Additional Efficacy and Safety Data
At a median follow‐up of 12.1 months, patients achieved a median OS that was not reached; the estimated 12‐month OS rate was 78.2% (95% CI, 51.36%-91.32%). The 12-month PFS rate was 58.2% (95% CI, 26.94%-79.98%).
In patients with extramedullary plasmacytoma (n = 4), 3 underwent at least one efficacy evaluation. One patient achieved an sCR, and 2 had a VGPR. Disease progression led to death in 1 patient in this subgroup prior to their first evaluation.
Any-grade TRAEs occurred in 85.0% of patients. Other common grade 3 or higher TRAEs included hypokalemia (10.0%), hyponatremia (5.0%), headache (5.0%), and diarrhea (5.0%).
Reference
Zhou YL, Zhang JQ, Wang W, et al. Bortezomib, mitoxantrone hydrochloride liposome, and dexamethasone for relapsed/refractory multiple myeloma: a multi-center, open-label phase I trial. Cancer Med. 2025;14(8):e70890. doi:10.1002/cam4.70890