Plasma cell leukaemia should no longer be considered a separate cancer but instead be classified as a subtype of high-risk multiple myeloma, say two international myeloma experts.
The distinction between plasma cell leukaemia and high-risk multiple myeloma has become increasingly difficult to justify and could be hampering both patient care and clinical research, according to a new Personal View published in The Lancet Haematology.
Mayo Clinic haematologists Professor S Vincent Rajkumar and Professor Shaji Kumar have proposed that plasma cell leukaemia be incorporated into high-risk multiple myeloma rather than continue to be regarded as a separate disease entity.
“We argue that plasma cell leukaemia must no longer be considered as a separate disease entity but as a type of high-risk multiple myeloma,” they wrote.
“With the adoption of more strict criteria for defining high-risk multiple myeloma and the relaxation of criteria in defining plasma cell leukaemia, the clinical implications of the terms have converged.
“Circulating plasma cells – the defining feature of plasma cell leukaemia – are present in almost all patients with multiple myeloma.
“Thus, the term plasma cell leukaemia merely reflects the high end of a continuum, with the main difference being a quantitative arbitrary threshold based on the percentage of circulating plasma cells.”
Plasma cell leukaemia has traditionally been distinguished from multiple myeloma by a high proportion of circulating clonal plasma cells, alongside its aggressive clinical course, short duration of treatment response, and generally poorer survival.
Until the past decade, diagnosis required at least 20% circulating plasma cells on a conventional peripheral white blood cell differential count, or an absolute plasma cell count above 2000 × 10⁹/L.
The International Myeloma Working Group subsequently lowered the circulating plasma cell threshold to at least 5%.
At the same time, definitions of high-risk multiple myeloma have tightened. The authors noted that 2025 International Myeloma Society and IMWG criteria generally required two high-risk cytogenetic lesions rather than one, leaving an estimated 15-25% of myeloma classified as high risk and bringing its adverse prognosis closer to that associated with plasma cell leukaemia.
Professor Rajkumar and Professor Kumar argued that circulating plasma cells also did not represent a clear biological dividing line between the diseases.
Sensitive flow cytometry could detect circulating plasma cells in virtually all patients with multiple myeloma, suggesting that plasma cell leukaemia sat at the extreme end of a continuum rather than representing a fundamentally different malignancy.
There were nevertheless biological differences in frequency, the authors said.
The t(11;14) abnormality, for example, was present in around 50-60% of patients with plasma cell leukaemia compared with less than 25% of those with multiple myeloma, while high-risk genomic abnormalities were also more prevalent in plasma cell leukaemia.
But they argued that these differences did not alter the essential features of the malignancy or how it is managed.
They pointed to extramedullary myeloma as a precedent. Despite sharing aggressive biology and clinical behaviour with plasma cell leukaemia, extramedullary disease is considered a high-risk manifestation of multiple myeloma rather than a separate cancer.
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Reclassification could also have important implications for clinical trials. Plasma cell leukaemia is rare, making dedicated trials difficult, but grouping these patients with those who have high-risk multiple myeloma and extramedullary disease could create a larger population with biologically aggressive disease in which unified targeted treatment strategies could be tested.
The terminology may also unnecessarily alarm and confuse patients, the authors said.
“Internet searches of plasma cell leukaemia often provide outdated information on treatment and prognosis since advances made in multiple myeloma are not apparent if the two are not connected,” they wrote.
“Clinicians also need to be careful to emphasise that the phenotype of a high percentage of circulating plasma cells is associated with adverse outcomes, and that the high percentage of circulating plasma cells could be more aggressive than certain high-risk myeloma-defining abnormalities.”
The authors stopped short of calling for the term “plasma cell leukaemia” to be “fully retired” however.
Instead, they proposed retaining it as a descriptive label for a biological subtype of multiple myeloma that fulfils the criteria for high-risk disease.
Under their proposed classification, plasma cell leukaemia and multiple myeloma with extramedullary disease would join established high-risk categories based on cytogenetic and other abnormalities.
They acknowledged that the proposal carried risks, particularly if plasma cell leukaemia ultimately proved to have unique biology beyond high tumour burden and adverse cytogenetics.
Folding the condition into multiple myeloma could potentially make it harder to identify specific therapeutic targets or refine treatments for this group.
They said any reclassification would also need to be harmonised with WHO and IMWG disease definitions.
“Future studies should examine the clinical outcomes of patients who are considered to have high-risk myeloma by virtue of plasma cell leukaemia compared with those who have high-risk cytogenetics as defined by the IMS/IMWG criteria,” the authors concluded.
“These findings will give us a more granular view into optimal disease management, and help our efforts in overcoming adverse biology.”
