Minimal residual disease and log-reduction of plasma cells are associated with superior response after double autologous stem cell transplant in younger patients with multiple myeloma

Giovanni Rossi, Antonietta Pia Falcone, Maria Marta Minervini, Giovanni Pio De Cillis, Chiara De Waure, Leuconoe Grazia Sisti, Vincenzo Giambra, Daniela Valente, Vincenzo Chiello, Potito Rosario Scalzulli, Angelo Michele Carella, Nicola Cascavilla

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Abstract

Background: Optimization of chemotherapy regimens in the treatment of multiple myeloma (MM) has led to increase the frequency of cases with complete response (CR). Nonetheless, many MM patients still experience relapse, suggesting that CR represents a suboptimal response criteria, and that new therapeutic strategies are needed after single transplant. However, the role of double autologous stem cell transplant (ASCT) as new adjunctive strategy remains to be elucidated. Indeed, we investigated the role of minimal residual disease (MRD) and log-reduction of plasma cells (PCs) as predictors of outcome and in quantifying the degree of tumor reduction after any ASCT. Methods: MRD and log-reduction were assessed by a six-color flow cytometry (FC) at different time-points: post induction, post first-, and post-second ASCT. Results: A significant difference was evidenced among the three time points for both log-reduction (P < 0.001) and MRD (P = 0.005). MRD levels after double ASCT were lower than MRD levels achieved after single ASCT (P = 0.005) and after induction (P < 0.001). Frequency of MRD positive patients after double ASCT was significantly lower rather than after the first ASCT (P = 0.008) and after induction (P = 0.004). Interestingly, a significant reduction of PFS was observed in patients with an unfavorable-risk cytogenetic (P < 0.001) and patients with MRD over 0.01% (P = 0.001) as well as log-reduction lower than 2.57 (P = 0.018) after double ASCT. Conclusions: Our results show that a better clearance of myeloma cells is observed after the double ASCT, and a longer PFS is associated with a lower MRD.

Original languageEnglish
JournalCytometry Part B - Clinical Cytometry
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Residual Neoplasm
Plasma Cells
Multiple Myeloma
Stem Cells
Transplants
Cytogenetics
Flow Cytometry
Color
Recurrence
Drug Therapy

Keywords

  • double autologous stem cell transplant
  • flow cytometry
  • log-reduction
  • minimal residual disease
  • multiple myeloma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

@article{d5167b4a61474dd9874ebc23d301ac7c,
title = "Minimal residual disease and log-reduction of plasma cells are associated with superior response after double autologous stem cell transplant in younger patients with multiple myeloma",
abstract = "Background: Optimization of chemotherapy regimens in the treatment of multiple myeloma (MM) has led to increase the frequency of cases with complete response (CR). Nonetheless, many MM patients still experience relapse, suggesting that CR represents a suboptimal response criteria, and that new therapeutic strategies are needed after single transplant. However, the role of double autologous stem cell transplant (ASCT) as new adjunctive strategy remains to be elucidated. Indeed, we investigated the role of minimal residual disease (MRD) and log-reduction of plasma cells (PCs) as predictors of outcome and in quantifying the degree of tumor reduction after any ASCT. Methods: MRD and log-reduction were assessed by a six-color flow cytometry (FC) at different time-points: post induction, post first-, and post-second ASCT. Results: A significant difference was evidenced among the three time points for both log-reduction (P < 0.001) and MRD (P = 0.005). MRD levels after double ASCT were lower than MRD levels achieved after single ASCT (P = 0.005) and after induction (P < 0.001). Frequency of MRD positive patients after double ASCT was significantly lower rather than after the first ASCT (P = 0.008) and after induction (P = 0.004). Interestingly, a significant reduction of PFS was observed in patients with an unfavorable-risk cytogenetic (P < 0.001) and patients with MRD over 0.01{\%} (P = 0.001) as well as log-reduction lower than 2.57 (P = 0.018) after double ASCT. Conclusions: Our results show that a better clearance of myeloma cells is observed after the double ASCT, and a longer PFS is associated with a lower MRD.",
keywords = "double autologous stem cell transplant, flow cytometry, log-reduction, minimal residual disease, multiple myeloma",
author = "Giovanni Rossi and Falcone, {Antonietta Pia} and Minervini, {Maria Marta} and {De Cillis}, {Giovanni Pio} and {De Waure}, Chiara and Sisti, {Leuconoe Grazia} and Vincenzo Giambra and Daniela Valente and Vincenzo Chiello and Scalzulli, {Potito Rosario} and Carella, {Angelo Michele} and Nicola Cascavilla",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/cyto.b.21755",
language = "English",
journal = "Cytometry Part B - Clinical Cytometry",
issn = "1552-4949",
publisher = "Wiley-Liss Inc.",

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TY - JOUR

T1 - Minimal residual disease and log-reduction of plasma cells are associated with superior response after double autologous stem cell transplant in younger patients with multiple myeloma

AU - Rossi, Giovanni

AU - Falcone, Antonietta Pia

AU - Minervini, Maria Marta

AU - De Cillis, Giovanni Pio

AU - De Waure, Chiara

AU - Sisti, Leuconoe Grazia

AU - Giambra, Vincenzo

AU - Valente, Daniela

AU - Chiello, Vincenzo

AU - Scalzulli, Potito Rosario

AU - Carella, Angelo Michele

AU - Cascavilla, Nicola

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Optimization of chemotherapy regimens in the treatment of multiple myeloma (MM) has led to increase the frequency of cases with complete response (CR). Nonetheless, many MM patients still experience relapse, suggesting that CR represents a suboptimal response criteria, and that new therapeutic strategies are needed after single transplant. However, the role of double autologous stem cell transplant (ASCT) as new adjunctive strategy remains to be elucidated. Indeed, we investigated the role of minimal residual disease (MRD) and log-reduction of plasma cells (PCs) as predictors of outcome and in quantifying the degree of tumor reduction after any ASCT. Methods: MRD and log-reduction were assessed by a six-color flow cytometry (FC) at different time-points: post induction, post first-, and post-second ASCT. Results: A significant difference was evidenced among the three time points for both log-reduction (P < 0.001) and MRD (P = 0.005). MRD levels after double ASCT were lower than MRD levels achieved after single ASCT (P = 0.005) and after induction (P < 0.001). Frequency of MRD positive patients after double ASCT was significantly lower rather than after the first ASCT (P = 0.008) and after induction (P = 0.004). Interestingly, a significant reduction of PFS was observed in patients with an unfavorable-risk cytogenetic (P < 0.001) and patients with MRD over 0.01% (P = 0.001) as well as log-reduction lower than 2.57 (P = 0.018) after double ASCT. Conclusions: Our results show that a better clearance of myeloma cells is observed after the double ASCT, and a longer PFS is associated with a lower MRD.

AB - Background: Optimization of chemotherapy regimens in the treatment of multiple myeloma (MM) has led to increase the frequency of cases with complete response (CR). Nonetheless, many MM patients still experience relapse, suggesting that CR represents a suboptimal response criteria, and that new therapeutic strategies are needed after single transplant. However, the role of double autologous stem cell transplant (ASCT) as new adjunctive strategy remains to be elucidated. Indeed, we investigated the role of minimal residual disease (MRD) and log-reduction of plasma cells (PCs) as predictors of outcome and in quantifying the degree of tumor reduction after any ASCT. Methods: MRD and log-reduction were assessed by a six-color flow cytometry (FC) at different time-points: post induction, post first-, and post-second ASCT. Results: A significant difference was evidenced among the three time points for both log-reduction (P < 0.001) and MRD (P = 0.005). MRD levels after double ASCT were lower than MRD levels achieved after single ASCT (P = 0.005) and after induction (P < 0.001). Frequency of MRD positive patients after double ASCT was significantly lower rather than after the first ASCT (P = 0.008) and after induction (P = 0.004). Interestingly, a significant reduction of PFS was observed in patients with an unfavorable-risk cytogenetic (P < 0.001) and patients with MRD over 0.01% (P = 0.001) as well as log-reduction lower than 2.57 (P = 0.018) after double ASCT. Conclusions: Our results show that a better clearance of myeloma cells is observed after the double ASCT, and a longer PFS is associated with a lower MRD.

KW - double autologous stem cell transplant

KW - flow cytometry

KW - log-reduction

KW - minimal residual disease

KW - multiple myeloma

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U2 - 10.1002/cyto.b.21755

DO - 10.1002/cyto.b.21755

M3 - Article

JO - Cytometry Part B - Clinical Cytometry

JF - Cytometry Part B - Clinical Cytometry

SN - 1552-4949

ER -