Safety and efficacy of autologous hematopoietic stem cell transplantation followed by CAR-T therapy in patients with high-risk or advanced plasma cell neoplasms

Abstract Introduction Autologous hematopoietic stem cell transplantation (auto-HSCT) remains an important strategy for prolonging survival in patients with plasma cell neoplasms. Chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) has demonstrated promising efficacy in multiple myeloma (MM). However, the prognosis of patients with high-risk or advanced plasma cell neoplasms following auto-HSCT remains poor, and CAR-T therapy alone offers limited benefit in this population.Aim To preliminarily assess the safety and efficacy of auto-HSCT followed by CAR-T therapy in patients with high-risk or advanced plasma cell neoplasmsMethods This retrospective study analyzed clinical data from patients treated at the Department of Hematology, Shaanxi Provincial People's Hospital, between March 2024 and June 2025. Patients received sequential auto-HSCT followed by BCMA-targeted CAR-T therapy. Demographics, hematopoietic engraftment data, adverse events, and treatment responses were collected. Follow-up was conducted until July 25, 2025, or until death.Results1) Patient Characteristics A total of 14 patients with high-risk or advanced plasma cell neoplasms underwent Auto-HSCT followed by CAR-T therapy. The cohort included 7 males and 7 females, with a median age of 57 years (range: 44–66). Among them, 28.6% had previously undergone auto-HSCT, and 14.2% had received CAR-T therapy. Notably, 50% had TP53 deletions, 50% had extramedullary disease, and 28.6% were diagnosed with primary plasma cell leukemia.2) Conditioning Regimen, Cell Infusion, and Engraftment Patients received melphalan 200 mg/m² as a conditioning regimen on day -1, followed by infusion of autologous hematopoietic stem cells on day 0. The median number of CD34⁺ cells infused was 3.48 ×10⁶/kg (range: 1.86–6.46 ×10⁶/kg), and the median mononuclear cell count was 6.19 ×10⁸/kg (range: 3.14–16.63 ×10⁸/kg). CAR-T cells were administered sequentially on a median of day +4 (range: +1 to +8) post-transplantation. Corticosteroids were used to control fever in 28.6% of patients, and IL-6 receptor inhibitors were administered in 21.4% to congtrol CRS. Median neutrophil engraftment occurred in 13 (range: 9–20)days and platelet engraftment in 12 (range: 0–19)days3) Adverse Events All patients (100%) experienced cytokine release syndrome (CRS); 92.8% were grade 1–2, and 7.2% were grade 3. Immune effector cell-associated neurotoxicity syndrome (ICANS) of grade 1–2 occurred in 28.5% of patients. Infections occurred in 35.7% of patients, all of which were below grade 3. One male patient with primary plasma cell leukemia and extramedullary disease achieved complete remission but later died from a massive cerebral infarction.4) Efficacy Evaluation All patients were followed for more than 3 months, and 42.9% were followed for more than 6 months. Excluding the patient who died of stroke, 92.85% (13/14) achieved complete remission (CR) within 3 months post-treatment. During months 3–6 of follow-up, disease progression occurred in 2 patients. Among the 6 patients followed for more than 6 months, all remained in remission throughout the follow-up period.ConclusionSequential BCMA-targeted CAR-T therapy following Auto-HSCT in patients with high-risk or advanced plasma cell neoplasms is associated with rapid hematopoietic recovery, manageable adverse effects, and favorable treatment responses. This therapeutic strategy may represent a promising option for selected patients with aggressive plasma cell malignancies.