Management of Primary Plasma Cell Leukemia Remains Challenging Even in the Era of Novel Agents

Abstract

Primary plasma cell leukemia (PCL) is a rare and aggressive variant of multiple myeloma (MM). PCL is characterized by peripheral blood involvement by malignant plasma cells and an aggressive clinical course leading to poor survival. There is considerable overlap between MM and PCL with respect to clinical, immunophenotypic, and cytogenetic features, but circulating plasma cell count exceeding 20% of peripheral blood leukocytes or an absolute plasma cell count of >2000/mm3 distinguishes it from MM. After initial stabilization and diagnosis confirmation, treatment of PCL in a fit patient typically includes induction combination chemotherapy containing novel agents typically, with proteasome inhibitors (such as bortezomib) and immunomodulatory drugs (eg, lenalidomide), followed by autologous hematopoietic stem cell transplant (HSCT) and multidrug maintenance therapy using novel agents post-HSCT. Long-term outcomes have improved employing this strategy but the prognosis for non-HSCT candidates remains poor and new approaches are needed for such PCL patients not eligible for HSCT. Here, we report a case of primary PCL, and a comprehensive and up to date review of the literature for diagnosis and management of PCL. We also present the findings of Positron Emission Tomography (PET) scan. Since PCL is often associated with extra-medulary disease, including PET scan at the time of staging and restaging may be a novel approach particularly to evaluate the extra-medullary disease sites.

Prognostic value of circulating plasma cells detected by flow cytometry in newly diagnosed multiple myeloma patients: a systematic review and meta-analysis

“…Once the CPC count exceeding 20% or an absolute plasma cell count of >2000/mm evaluated by morphology, it is defined as plasma cell leukaemia (PCL). Although there is considerable overlap between MM and PCL with respect to clinical, immunophenotypic and cytogenetic features, PCL is more aggressive and has poorer survival 11. In 2021, the International Myeloma Working Group (IMWG) recommended that PCL should be redefined as the presence of ≥5% CPCs evaluated by morphology,12 for NDMM with 5%–19% CPCs showed similar poor survival with PCL 13 14.…”

“…Although there is considerable overlap between MM and PCL with respect to clinical, immunophenotypic and cytogenetic features, PCL is more aggressive and has poorer survival. 11 In 2021, the International Myeloma Working Group (IMWG) recommended that PCL should be redefined as the presence of ≥5% CPCs evaluated by morphology, 12 for NDMM with 5%–19% CPCs showed similar poor survival with PCL. 13 14 There was even a study proposed to define 2% of CPCs by using sensitive multiparameter FCM as a new cut-off for ultra-high-risk MM resembling behaviour of primary PCL.…”

A Clinical Perspective on Plasma Cell Leukemia: A Single-Center Experience

“…The optimal treatment regimens and sequencing are less well-defined for PCL as compared to MM. Despite the progress seen in MM, a parallel advancement has not been seen in PCL, in part due to the low incidence as well as the rarity of studies including PCL [ 17 , 18 ]. The goal of this large single-institution retrospective study is to describe the clinical presentation and treatment impact on overall survival in 104 patients with pPCL and sPCL (defined ≥5% CPC) as well as in patients with 1–4% CPCs.…”

Genomics of Plasma Cell Leukemia

“…Higher tumor burden and proliferation activity of PCL are manifested by greater levels of B2-microglobulin and lactate dehydrogenase (LDH). Extramedullary involvement (lymph nodes, liver, spleen, pleura, and central nervous system) at diagnosis is more common in pPCL and sPCL than in MM, but osteolytic lesions are more frequent in sPCL and MM than in pPCL [8][9][10][11][12][13].…”