Patterns of Progression and Clinical Outcomes After First Progression in Patients With Primary Plasma Cell Leukemia

Primary plasma cell leukemia (pPCL) is a rare and aggressive plasma cell disorder with inferior outcomes compared with multiple myeloma (MM). However, studies describing outcomes after first progression and subsequent lines of therapy remain limited. We retrospectively analyzed 104 patients with pPCL who progressed after first-line therapy treated at one comprehensive cancer center between 2006 and 2024. Clinical characteristics, treatments, time to next treatment (TTNT), and overall survival (OS) were assessed using Kaplan-Meier methods. All pPCL patients received novel agent-based induction. At the time of analysis, 63% had died; median OS was 39 months. High-risk cytogenetics were present in 71%. The median TTNT after first-line therapy was 10 months. Symptomatic progression occurred in 29% of patients and was associated with significantly inferior subsequent OS (13 vs. 34 months) compared with those experiencing asymptomatic biochemical progression. The TTNT progressively shortened with subsequent lines of therapy (3rd line: 6 months; 4th line: 4 months; 5th line: 3 months). Notable exceptions included pPCL patients with t(11;14) treated with anti-BCL-2-based regimens, who achieved a median TTNT of 13 months. Additionally, 24 patients received anti-BCMA CAR T-cell therapy. With a median follow-up of 21 months, their median TTNT was 32 months. pPCL is characterized by frequent disease progression and diminishing response duration with successive therapeutic lines. Symptomatic progression portends particularly poor outcomes. Anti-BCL-2-based therapy in t(11;14) disease and anti-BCMA CAR T-cell therapy appear to provide more durable disease control and represent important advances for the management of progressed pPCL.