P-344: A single-arm prospective study of the combination of KAPD induction with or without ASCT and KP maintenance for newly diagnosed extramedullary multiple myeloma

Introduction: Extramedullary disease(EMD) is associated with poor outcome in newly diagnosed multiple myeloma(NDMM). Mainly derived from retrospective studies, intensive anti-myeloma/anti-lymphoma regimens,novel-agent combinations, and autologous stem cell transplantation(ASCT) are currently proposed as theoretical treatment options. The paucity of prospective studies makes it difficult to justify strong recommendations for any treatment approach for extramedullary MM(EMM). This study will assess the efficacy and safety of the combination of the combination of carfilzomib/liposomal adriamycin/pomalidomide/dexamethasone (KAPD) induction with or without ASCT and carfilzamib/pomalidomide maintenance for ND EMM.

Methods: This is a single-arm prospective study. Key inclusion criteria were: (1) NDMM with EMD,as defined by one of the following: 1) the presence of extramedullary lesions in the paraskeletal areas or soft tissues/organs detected by MRI or PET-CT or CT imaging; 2) biopsy proved plasmacytoma of the extramedullary lesion; (2) Age: 18-70 years old; (3) A "measurable lesion": at least one extramedullary lesion ≥1.0 cm in length. Treatment strategy includes KAPD induction (4 cycles), tandem ASCT for transplantation eligible and another 4 cycles of KAPD for transplantation ineligible patients, followed with KP(carfilzomib-pomalidomide) maintenance. The primary endpoint is overall response rate. Here, we report the preliminary data of efficacy and safety analysis of KAPD induction.

Results: extramedullary disease(EMB) were included from Dec 2023 to May 2024. Median age was 47(range 43-62). ISS stage 3 and RISS stage 3 were present in 2 (28.6%) and 0(0%) patients. High risk cytogenetics were presented in 4(57.1%) patients, including 17p deletion (n=1, 14.3%), 1p32 deletion (n=1, 14.3%), ,and 1q21+ (n=4, 57.1%) . Three patients completed 4 cycles of KAPD induction, and 1 patients completed stem cell collection. One patients discontinued treatment due to severe adverse event (neutropenic fever, n=1). Grade 3-4 treatment related adverse event were neutropenia (28.6%), thrombocytopenia (14.3%) , neutropenic fever (14.3%), and drug fever (14.3%). Rate of any TEAEs leading to definitive discontinuation was 14.3%, and rate of life-threatening TEAEs was 0%. Among 4/7 evaluable patients post induction, overall response rate was 100.0%, including 25.0% MRD (NGF, 10-5) negativity, 25.0 % ≥CR, 75.0 % ≥VGPR, and 100.0% ≥PR. Among 3/7 EMD response evaluable patients post induction, overall EMD response rate of KAPD induction was 66.7%, including 2(66.7%) PR.

Conclusions: KAPD as a induction regimen is safe and facilitates profound responses in patients with newly-diagnosed EMM. The study is ongoing, longer follow-up is needed to evaluate safety and efficacy of the comprehensive treatment approach with KAPD induction, with or without ASCT and carfilzamib/pomalidomide maintenance for newly diagnosed EMM.