The Mayo Clinic recently announced recommendations for revising the diagnostic criteria of plasma cell leukemia (PCL), with the focus of improving multiple myeloma (MM) management in patients at risk for poor outcomes. Based on their research, patients who fall under the revised diagnostic definition of PCL should otherwise meet the current diagnostic criteria for MM while presenting with ≥5 percent circulating plasma cells (CPCs) on a conventional peripheral blood smear (Blood Cancer J 2018;8(12):116). This bears a stark contrast to the ≥20 percent CPC threshold in the current diagnostic criteria.
According to one of the study's researcher, S. Vincent Rajkumar, MD, the findings presented by the Mayo Clinic confirm results from two previously published studies on the diagnostic criteria for PCL. The first study, which involved 767 patients with MM and 108 CPCs at time of diagnosis (between 2004 and 2012), found that patients with ≥2 percent CPCs had worse survival when compared with patients <2 percent CPCs, whereas patients with ≥2 percent CPCs experienced similar survival to patients with traditionally diagnosed primary PCL (Ann Hematol 2015;94(2):257-264).
The second study, comprised of 482 MM patients with peripheral blood smears at time of diagnosis (between 2008 and 2013) as well as 100 patients with CPCs, found that the presence of 5-20 percent CPCs were associated with similar or worse survival versus patients with >30 percent CPCs (Haematologica 2017;102(6):1099-1104).
“We recommend that patients meeting criteria for multiple myeloma who have 5 percent or more circulating plasma cells on conventional white blood cell differential count be considered as having plasma cell leukemia,” Rajkumar, a hematologist at the Mayo Clinic and one of the authors of the new study calling for revision of PCL criteria, told Oncology Times.
“Previous criteria for plasma cell leukemia were more restrictive and missed many patients with the disease. Based on previous criteria, plasma cell leukemia diagnosis required 20 percent or more circulating plasma cells on conventional white blood cell differential count, or absolute circulating plasma cell count of 2000 x10(9) per liter or more. Our criteria show that the natural history and prognosis of patients with 5 percent or more circulating plasma cells on conventional white blood cell differential count is similar to patients with 20 percent or more circulating plasma cells.” Therefore, Rajkumar added, the criteria recommended by the Mayo Clinic may be more sensitive for the diagnosis of PCL.
To identify a new PCL diagnostic CPC threshold, Mayo Clinic researchers reviewed outcomes of MM patients who were diagnosed with the disease between 1971 and 2016 (n=176). At time of diagnosis, all patients had detectable CPCs.
In the total cohort, median overall survival (mOS) reached 1.1 years (95% CI, 0.8-1.4), a figure similar between patients with <5 percent CPCs (n=54, mOS=1.4 years; 95% CI, 0.7-2.0), 5-19 percent CPCs (n=63, mOS=1.1 years; 95% CI, 0.7-1.4), and ≥20 percent CPCs (n=59, mOS=1.1 years; 95% CI, 0.7-1.5; p=.349). Patients were stratified by <5 percent CPCs (mOS=1.4 years; 95% CI, 0.7-2.0) and ≥5 percent CPCs (mOS=1.1 years; 95% CI, 0.8-1.4; p=.154) and found that patients with ≥5 percent CPCs had poorer outcomes compared with 9,724 MM patients without CPCs at diagnosis between 1971 and 2016 (mOS=4.4 yrs; 95% CI, 4.3-4.5; p<.001).
Additionally, patients with ≥5 percent CPCs who were diagnosed after 2001 had lower survival versus patients with standard risk MM (mOS=1.4 years; 95% CI, 0.8-2.5 vs. mOS=7.5 years; 95% CI, 7.0-8.7, respectively) and high-risk MM (mOS=4.3 years; 95% CI, 3.5-4.9; p<.001).
“Patients meeting criteria for plasma cell leukemia have a survival that is significantly worse that patients with high-risk myeloma,” Rajkumar explained. “They are systematically excluded from many myeloma trials. To make a difference in outcome for these patients, we need to conduct trials designed for them, as well as include them in standard myeloma trials.”
The modified criteria, he noted, will allow researchers “to correctly diagnose these patients and we will also increase the likelihood of accrual to specific plasma cell leukemia trials. By obtaining a more accurate diagnosis, we can be more aggressive with treatment plans.”
While the new Mayo Clinic study may be promising, the inclusion of only patients from a single tertiary center may reduce the generalizability across the broader MM and PCL populations. Additionally, considering the lack of cytogenetic data in the majority of the cohort with PCL, the researchers were unable to evaluate any interaction between the percentage of CPCs and adverse cytogenetics.
Future directions for the prevised criteria look promising, particularly in regard to approval for widespread clinical use. Rajkumar told Oncology Times that the International Myeloma Working Group (IMWG) will soon be working on examining the results of three studies supporting the Mayo Clinic's revised threshold. Currently, the researchers expect that the new criteria will be endorsed by the IMWG.
“Additionally, we are working on research grants to understand the biology of this disease, including cytogenetics, mechanisms by which the plasma cells escape the marrow niche, and also planning clinical trials targeting this population of patients,” Rajkumar concluded.
Brandon May is a contributing writer.
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