Efficacy and Safety of the Mitoxantrone Hydrochloride Liposome Combination Regimen for the Treatment of High-Risk and/or Extramedullary Multiple Myeloma

Background Patients with high-risk and/or extramedullary multiple myeloma (MM) frequently encounter challenges related to treatment efficacy and are at an increased risk of relapse. Liposomal doxorubicin has been applied in MM and has shown encouraging efficacy and manageable safety. Mitoxantrone hydrochloride liposome (Lipo-MIT) has exhibited clinical benefits in leukemia and solid tumors due to higher concentration in tumor tissues and extended half-life, which prompted us to hypothesize its potential effectiveness in the management of MM. Aims To explore the efficacy and safety of Lipo-MIT combination regimen in high-risk and/or extramedullary multiple myeloma. Methods Thirteen eligible patients with high-risk and/or extramedullary MM received Lipo-MIT combination regimen at the Department of Hematology, Affiliated Hospital of Nantong University from August 2023 to July 2024. The primary endpoint was the objective response rate (ORR), which was assessed by the investigators. Secondary endpoints included 2-year progression-free survival (2-year PFS), 2-year overall survival (2-year OS), 2-year extramedullary relapse rate, duration of response (DoR), time to next treatment (TTNT), MRD negative rate and safety. Adverse events were graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) 5.0. The study was approved by the Institutional Ethics Committee (Reference number:2023-K183-02). Results A total of 13 patients were included in the study. The median age was 68 (51-80) years，9 females and 4 males. Among them, all samples existed in DS stage III and 6 patients existed in R-ISS stage III. Nine with high-risk types and 8 with extramedullary infiltration (EMM), comprising 5 cases of extramedullary extraosseous (EME) involvement and 3 cases of extramedullary bone-related (EMB) lesions. 9 newly diagnosed multiple myeloma (NDMM) patients received the Lipo-MIT, bortezomib, and dexamethasone (MVd) regimen as first-line treatment, 10 mg Lipo-MIT was administrated on day 1 and day 15. Four relapsed/refractory multiple myeloma (R/R MM) patients received the Lipo-MIT combination regimen in the third or fourth lines. All patients (ORR 90.9%) achieved objective response. In the NDMM group, 1 patient (11.1%) achieved complete response (CR), 7 (66.7%) achieved very good partial response (VGPR),and 2 (22.2%) achieved partial response (PR). For 8 EMM patients, 5 (62.5%) achieved VGPR in and 3 (37.5%) achieved PR. Among R/R MM patients, 3 achieved PR (75%, 3/4). Notably, a high-risk NDMM patient with renal insufficiency achieved VGPR and complete remission of renal symptoms after plasma exchange and completing 1 course of MVd. Another NDMM patient with pulmonary embolism achieved VGPR , the pulmonary branch thrombus largely disappeared after 4 courses of MVd. Median progression-free survival (mPFS) and median overall survival (mOS) were not reached. Hematologic adverse events (AEs) occurred in 9 cases, including leukopenia and anemia. Grade 2 or lower AEs were observed in 66.7% (6/9), while grade 3 or higher AEs occurred in 33.3% (3/9), which could be managed with drug therapy. Additionally, 3 patients underwent successful hematopoietic stem cell transplantation, and 2 patients received CAR-T cell therapy. Conclusion The Lipo-MIT combination regimen has demonstrated significant efficacy and relative safety in treating high-risk/extramedullary MM. The MVD regimen, on the other hand, lacks nephrotoxicity and thrombosis. The Lipo-MIT combination regimen does not significantly impact stem cell and PBMC collection. However, due to the limited sample size, further confirmation is necessary through large sample, multicenter studies. Additionally, long-term efficacy requires continued observation.