Mitoxantrone Hydrochloride Liposome, Proteasome Inhibitors, Pomalidomide and Dexamethasone Regimen in Multiple Myeloma Patients with Extramedullary Plasmacytoma in China

Background

Extramedullary plasmacytoma (EMP), as a poor prognostic factor, frequently occurres in multiple myeloma (MM) with adverse prognosis, more prospective longitudinal studies should be carried out for clinical practice. Mitoxantrone hydrochloride liposome (Lipo- MIT) has shown significant effects in a variety of solid tumors and leukemia accompanied by higher concentration in tumor tissues and extended half-life. Here we designed a pilot study to explore the efficacy and safety of Lipo-MIT, proteasome inhibitors (PIs), pomalidomide, and dexamethasone regimen in MM with EMP.

Methods

In this real-world single-arm study from six Chinese hospitals from March 2024 to July 2024, transplant-eligible (TE), transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM) and relapsed and refractory multiple myeloma (RRMM)patients with measurable EMP were enrolled in this study (ChiCTR2400087424), who received a 3-4 cycles Lipo-MIT-PIs-P-D regimen* (MVPD/MKPD), TE NDMM patients received auto stem cell transplantation, TIE MM patients received another 3-4 cycles MVPD/MKPD regimen then VP/KP regimen as maintenance. Primary endpoint: overall response rate (ORR) of two cycles regimen. Key endpoints: progression-free survival (PFS), therapy duration and adverse event (AE). Both hematological response and EMP response were assessed by the International Myeloma Working Group (IMWG) criteria.

Results

21 patients were enrolled in this study, 38% (8/21) of them were NDMM, 33% (7/21) of them were FRMM (first relapsed multiple myeloma), others were RRMM; the median age was 62 years old; 52% (11/21) male; IgG/IgA/light chain/ nonsecretory (48%/28%/14%/10%). R-ISS stage was estimated for patients (stage I/II/III 14%/67%/19%). 50% high risk (4/8) were qualified by metaphase fluorescence in situ hybridization (M-FISH) according to Mayo Clinic risk stratification in NDMM. All patients with at least one kind of EMP were followed, 76% (16/21) patients with paraskeletal plasmacytoma, including 50% (6/12) with high Ki 67 index and 29% (6/21) with large mass (diameter more than 5cm); 24% (5/21) with soft-tissue plasmacytoma, and with no plasma cell leukemia. PIs resistance was 57%, IMiDs resistance was 57%, and CD38 antibody resistance was 29% in the previous treatment of RRMM.

By the data cutoff of July 30th, 2024, all enrolled patients received a median of 1-5 cycles of MVPD/MKPD regimen, median follow-up was 3 months, median PFS and OS have not reached. The ORR was 81% (17/21), 29% CR (6/21) at the end of two cycles of regimen, the ORR after four cycles of regimen with or without radiation therapy was 83% (10/12), 42% CR (5/12) at the end of chemotherapy and 58% CR (7/12) after radiation. The most common AEs at all grades (81%, 17/21) were leukocytopenia (81%), thrombocytopenia (71%), as well as respiratory infection (29%), peripheral neuropathy (29%), dose reduction or drug withdrawal of pomalidomide were occurred in 29% patients.

Conclusion

This study revealed promising results of early response and efficacy of Lipo-MIT-PIs-P-D regimen in MM with EMP, which could be further explored in prospective phase 3 studies.

*：Lipo-MIT-PIs-P-D regimen (MVPD/MKPD): Lipo-MIT, 12mg/m ²; bortezomib 1.3mg/m2, d1,4,8,11(change to carfilzomib cause of bortezomib resistance or intolerance), pomalidomide: 4mg d1-14; dexamethasone: 20mg d1-2,4-5,8-9,11-12. After three cycles of regimen, bortezomib changed to 1.3mg/m2, d1,8,15,22. Half dose of MVPD/MKPD in older Patients (more than 70 years old).

No relevant conflicts of interest to declare.