PF555 PROGNOSTIC VALUE OF NEXT GENERATION FLOW MONITORING CIRCULATING TUMOR PLASMA CELLS IN PERIPHERAL BLOOD ON MYELOMA PATIENTS AFTER TREATMENT
Authors: Flores L. Sanoja , Montero J. Flores , Contreras‐Sanfeliciano T. , Puig N. , Mateos A. Corral , Sánchez O. García , Campelo M. Díez , Pontes R. , Martín L. García , Alonso J.M. Alonso , Mateo A. García , Franco C. Aguilar , Labrador J. , García A. Báez , González M. , Mateos M.V. , Durie B. , Van Dongen J. , Orfao A. 
Published: June 2019

Background:

After the introduction of novel and more‐effective therapies in multiple myeloma (MM) the number of patients achieving high quality responses has substantially increased, demanding the implementation of more sensitive methods to evaluate persistence of minimal residual disease (MRD) in bone marrow (BM) at very low levels. We have recently developed the Next Generation Flow (NGF) approach to assess medullary MRD in MM patients, which became the reference methodology by the International Myeloma Working Group (IMWG) to evaluate flow‐MRD status. Despite the clinical prognostic value of NGF BM MRD, sampling is limited to (few) specific timepoints throughout therapy. Nowadays, more frequent and less‐invasive approaches are used for a closer follow‐up (e.g., serum immunofixation ‐sIF‐). More recently, NGF has successfully been applied for the detection of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of plasma cells neoplasms patients at diagnosis, providing significant diagnostic and risk stratification information; however, the prognostic impact of PB CTPC detection in MM patients after therapy has not been deeply explored.

Aims:

Here, we investigated the value of NGF for PB CTPC detection in post‐therapeutic MM patients and its relationship with paired BM MRD and sIF evaluations.

Methods:

Overall, we studied 309 paired PB and BM samples from 128 treated MM patients discriminated according to the IMWG response criteria. Both PB and BM samples were processed using the EuroFlow NGF MM‐MRD approach in parallel to sIF. The Kaplan–Meier method and the log‐rank test were used to plot and compare progression‐free survival (PFS) curves between groups. PFS was defined as time from sample evaluation to either disease progression or death by any reason. For all statistical analyses the SPSS (v. 23; IBM, Armonk, NY), was used. Statistical significance was set at p values <0.05. Written informed consent was given by each patient prior to entering the study according to the Declaration of Helsinki.

Results:

Altogether, 26% of all MM analyzed (33/128) showed CTPC+ in PB. In turn, 49/128 (38%) of patients were BM MRD+ without CTPC in PB. Of note, CTPC were never detected in PB in the absence of BM involvement (n = 0/128). In addition, sIF+ results were present in close to one third of patients without PB CTPC (39/128; 30%), and 26% (10/39) of them being BM MRD−. Focusing on complete response (CR) or stringent CR (sCR) MM patients (i.e, sIF−; n = 65), 17% (11/65) were PB CTPC+. Median percentages and absolute CTPC counts in PB were significantly lower for those CR/sCR MM patients than observed in the whole cohort of CTPC+ cases (p < 0.05): 0.0002% (range: <0.0001%>0.007%) and 15 CTPC/mL of PB (range: <5–457 CTPC/mL) vs 0.002% (range: <0.0001%>0.6%) and 96 CTPC/mL of PB (range: <5–18,352 CTPC/mL), respectively. Noteworthy, from the prognostic point of view, MM patients who were PB CTPC+ showed significantly shorter PFS rates vs PB CTPC− cases regardless of BM‐MRD status, both in the whole patient series and within CR/sCR patients (median PFS of 11 months vs not reached, respectively; p<0.0001 in both comparisons).

Summary/Conclusion:

The high‐sensitive NGF approach allowed detection of PB CTPC in more than a quarter MM cases after treatment and in 17% of those in CR/sCR. Detection of PB CTPC identified a poor prognostic subgroup of patients (≈80% of relapse or death at 2 years). In summary, NGF can be applied in PB for non‐invasive monitoring of post‐therapeutic MM patients and provides complementary prognostic value to BM MRD and sIF.

image