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In patients with plasma cell disorders , disease burden assessments and molecular subtyping are typically performed by invasive bone marrow sampling . According to a study presented at the AACR Annual Meeting , measuring levels of circulating multiple myeloma cells ( CMMCs ) can be a useful and non-invasive tool for monitoring and characterizing a range of plasma cell disorders .
“ CMMCs have been detected in elevated numbers in the peripheral blood of patients with plasma cell disorders using flow cytometry or circulating cell enrichment platforms ,” the authors , led by Brad Foulk , of Janssen Research & Development , wrote . To determine CMMCs ’ ability to characterize disease , Mr . Foulk and colleagues developed “ an automated [ circulating tumor cell ] assay to enrich , enumerate , and perform a triplex fluorescence in situ hybridization assay for t ( 4 ; 14 ), t ( 14 ; 16 ), and del17p on CMMC ( CD138 +, CD38 +, CD45-CD19- ) isolated from a 4 mL peripheral blood sample .” The assay was tested in three patient cohorts :
• Cohort 1 : 698 patients with newly diagnosed multiple myeloma enrolled in the Multiple Myeloma Research Foundation ’ s CoMMpass study ( a study that is mapping genomic profiles of patient tissue in an effort to understand response to MM treatments )
• Cohort 2 : 79 patients with intermediate / high-risk smoldering multiple myeloma ( SMM ) enrolled in a phase II study of siltuximab
• Cohort 3 : 35 patients across the plasma cell disease spectrum ( with an emphasis on monoclonal gammopathy of undetermined significance [ MGUS ] and SMM )
In Cohort 1 , one or more CMMC per 4 mL of blood were detected in 98 percent ( n = 684 / 698 ) of patients , with a median CMMC count of 413 per 4 mL of blood . When patients achieved remission , CMMC counts decreased significantly from baseline ( p < 0.001 ). Lower CMMC counts (< 100 / mL of blood ) at remission were also associated with improved progression-free survival and overall survival , compared with patients who had CMMC counts > 100 / mL blood at remission .
CMMC FISH results , available in 57 patients , were highly correlated with bone marrow FISH results and bone marrow copy number variation / RNA sequencing for detecting t ( 4 ; 14 ), t ( 14 ; 16 ), and del17p : 85 percent , 91 percent , and 80 percent agreement for FISH , and 81 percent , 91 percent , and 95 percent agreement for CNV / RNA sequencing , respectively .
In Cohort 2 , one or more CMMC per 4 mL of blood was detected at baseline in 94 percent of patients ( n = 74 / 49 ), with a
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THE FUTURE OF PERSONALIZED THERAPY IN CANCER TREATMENT
t this year ' s American Association for Cancer Research ( AACR ) Annual Meeting , scientists and physicians gathered in New Orleans , Louisiana , to share advances in research that could translate into advances in patient care . Much of the data presented at the meeting focused on the future of personalized therapy in cancer treatment — a theme Vice President Joe Biden touched on in his plenary address .
Here , we present research highlights from the meeting , including CAR T-cell therapy in patients with non-Hodgkin lymphoma , spliceosome inhibition to treat patients with acute leukemia , and novel targets in multiple and smoldering myeloma .
Vice President Joe Biden delivers his plenary address to AACR attendees .
Circulating Multiple Myeloma Cells a Useful , Non-Invasive Prognostic Marker for Plasma Cell Disorders median CMMC count of 100 per 4 mL of blood . Patients in the placebo arm of the study who had disease progression had significantly higher CMMC counts than those whose disease had not progressed ( p = 0.031 ). Results from the standard metrics of disease burden ( bone marrow plasma cells and serum M protein levels ), however , showed no statistically significant differences in CMMC counts between patients who progressed ( p = 0.068 ) and those who did not progress ( p = 0.070 ).
In Cohort 3 , the researchers also found that CMMC counts were associated with the disease burden of patients ( no additional data provided ).
“ In multiple myeloma , CMMC may be a useful prognostic marker at remission to delineate those patients whose disease is at risk for relapse ,” the researchers concluded . “ In SMM , CMMC may be useful for predicting patients at risk for progression to multiple myeloma .” Though potentially clinically significant , these findings need to be validated prospectively .
REFERENCE
Foulk B , Schaffer M , Gross S , et al . Peripheral blood circulating multiple myeloma cells ( CMMCs ) correlate with disease burden and can be used to characterize high-risk cytogenetics in newly diagnosed and smoldering myeloma . Abstract 3163 . Presented at the AACR Annual Meeting , April 19 , 2016 ; New Orleans , LA .
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