The Clinical Impact of Macrofocal Disease in Multiple ... · Myeloma Institute University of...
1
Myeloma Institute University of Arkansas for Medical Sciences The Clinical Impact of Macrofocal Disease in Multiple Myeloma Differs between Presentation and Relapse Leo Rasche 1 , Amy Buros 1 , Niels Weinhold 1 , Caleb Stein 1 , James McDonald 2 , Shweta Chavan 1 , Edgardo Angtuaco 2 , Sharmilan Thanendrarajan 1 , Carolina Schinke 1 , Shmuel Yaccoby 1 , Joshua Epstein 1 , Frits van Rhee 1 , Maurizio Zangari 1 , Bart Barlogie 1 , Brian Walker 1 , Faith Davies 1 , Gareth Morgan 1 1 UAMS Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 2 Radiology Department, University of Arkansas for Medical Sciences, Little Rock, AR, USA What is macrofocal myeloma/ a macrofocal pattern? MACROFOCAL AT PRESENTATION BACKGROUND MACROFOCAL DURING THERAPY xx CONCLUSION + Macrofocal Myeloma at presentation has an excellent prognosis Macro MM at presentation seems to be an early stage of MM with an excellent prognosis. In contrast, a macrofocal pattern at restaging is associated with poor prognosis and early relapse. At this disease stage residual focal lesions may represent drug resistant clones. Nodular growth of low risk clones Drug-responsive Cure Macrofocal lesion at presentation Macrofocal lesion at later stages PET-CT DWIBS Bone marrow infiltration at the iliac crest < 10% Evolution model of MM Macrofocal Multiple Myeloma (macro MM) is defined by the presence of focal lesions and the absence of significant intervening bone marrow (BM) infiltration. At presentation, macro MM constitutes a distinct disease entity likely being associated with a favorable prognosis, although current evidence to support this is limited. Following first-line therapy, macrofocal patterns of disease emerge also in patients that initially presented with classical MM. In these patients the systemic BM involvement disappears in follow up examinations during treatment whereas focal lesions persist. In a third scenario, macrofocal patterns occur at overt relapse representing a patchy type of MM progression. The prognostic impact of a macrofocal pattern at these various disease stages is largely unknown. MACROFOCAL RELAPSE In macrofocal MM focal lesions frequently occur on a MGUS background Macrofocal MM at presentation Matched controls with classical MM Progression free survival Gene expression analysis A: Clinical outcome in macro MM is significantly favorable compared to a matched control group (matched for age, Ig type and treatment). B/C: Outcomes in GEP70 low risk and ISS stage 1 patients; D: Impact of number of focal lesion on outcome A B C D Paired gene expression profiles of macrofocal lesions and random bone marrow aspirates were used for proliferation and expression studies. 94% of patients were GEP70 low risk Paired samples were available in 16 cases No difference in proliferation index between macrofocal lesions and randomly taken bone marrow aspirates After correction for multiple testing no differentially expressed genes No differentially expressed adhesion molecules (27 MM- relevant tested) Macrofocal patterns at restaging during initial therapy showed a 80% cumulative relapse incidence. The outcome of these cases was significantly worse in comparison to matched controls (P=0.02 and 0.02 for PFS and OS, respectively) Nodular growth of high risk clones Drug-resistant Extramedullary involvement 25% of relapsed patients presented with a macrofocal pattern; a surprisingly high proportion. Extramedullary involvement was common (41%). Of note, 36% of patients repeatedly showed macrofocal patterns at subsequent relapses. PFS and OS at 2 years from macrofocal relapse were 24% and 39%, respectively. Macrofocal pattern at restaging predicts early relapse A macrofocal pattern at relapse is frequent Plasma cell purification (CD138 selection) Diagnostic aspirate from iliac crest At overt relapse a macrofocal pattern was frequently seen, highlighting the need to integrate advanced imaging tools into the standard work up and indicating an important confounder of standard minimal residual disease diagnostics in Multiple Myeloma.
Transcript of The Clinical Impact of Macrofocal Disease in Multiple ... · Myeloma Institute University of...
Myeloma InstituteUniversity of Arkansas for Medical Sciences
The Clinical Impact of Macrofocal Disease in Multiple Myeloma
Differs between Presentation and Relapse Leo Rasche1, Amy Buros1, Niels Weinhold1, Caleb Stein1, James McDonald2, Shweta Chavan1, Edgardo Angtuaco2, Sharmilan Thanendrarajan1, Carolina Schinke1, Shmuel Yaccoby1,
Joshua Epstein1, Frits van Rhee1, Maurizio Zangari1, Bart Barlogie1, Brian Walker1, Faith Davies1, Gareth Morgan1
1UAMS Myeloma Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 2Radiology Department, University of Arkansas for Medical Sciences, Little Rock, AR, USA
What is macrofocal myeloma/ a macrofocal pattern?
MACROFOCAL AT PRESENTATIONBACKGROUND
MACROFOCAL DURING THERAPY
xx
CONCLUSION
+
Macrofocal Myeloma at presentation has an excellent prognosis
Macro MM at presentation seems to be an early stage of MM with an
excellent prognosis. In contrast, a macrofocal pattern at restaging is
associated with poor prognosis and early relapse. At this disease stage
residual focal lesions may represent drug resistant clones.
Nodular growth of low risk clones
Drug-responsive
Cure
Macrofocal lesion at
presentation
Macrofocal lesion at
later stages
PET-CT DWIBS
Bone marrow infiltration at the iliac crest < 10%
Evolution model of MMMacrofocal Multiple Myeloma (macro MM) is defined by
the presence of focal lesions and the absence of
significant intervening bone marrow (BM) infiltration. At
presentation, macro MM constitutes a distinct disease
entity likely being associated with a favorable prognosis,
although current evidence to support this is limited.
Following first-line therapy, macrofocal patterns of disease
emerge also in patients that initially presented with
classical MM. In these patients the systemic BM
involvement disappears in follow up examinations during
treatment whereas focal lesions persist. In a third scenario,
macrofocal patterns occur at overt relapse representing a
patchy type of MM progression. The prognostic impact of a
macrofocal pattern at these various disease stages is
largely unknown.
MACROFOCAL RELAPSE
In macrofocal MM focal lesions frequently occur on a
MGUS background
Macrofocal MM at presentation Matched controls with classical MM
Progression free survival
Gene expression analysis
A: Clinical outcome in macro MM is significantly favorable compared to a matched control group (matched for age, Ig type
and treatment). B/C: Outcomes in GEP70 low risk and ISS stage 1 patients; D: Impact of number of focal lesion on outcome
A
B C D
Paired gene expression profiles of macrofocal lesions and random bone marrow aspirates were used for
proliferation and expression studies.
94% of patients were GEP70 low risk
Paired samples were available in 16 cases
No difference in proliferation index between macrofocal lesions and
randomly taken bone marrow aspirates
After correction for multiple testing no differentially expressed genes
No differentially expressed adhesion molecules (27 MM- relevant
tested)
Macrofocal patterns at restaging
during initial therapy showed a
80% cumulative relapse
incidence. The outcome of these
cases was significantly worse in
comparison to matched controls
(P=0.02 and 0.02 for PFS and
OS, respectively)
Nodular growth of high risk clones
Drug-resistant
Extramedullary involvement
25% of relapsed patients
presented with a macrofocal
pattern; a surprisingly high
proportion. Extramedullary
involvement was common
(41%). Of note, 36% of
patients repeatedly showed
macrofocal patterns at
subsequent relapses. PFS
and OS at 2 years from
macrofocal relapse were
24% and 39%, respectively.
Macrofocal pattern at restaging predicts early relapse A macrofocal pattern at relapse is frequent
Plasma cell
purification
(CD138 selection)
Diagnostic aspirate from iliac crest
At overt relapse a macrofocal pattern was frequently seen,
highlighting the need to integrate advanced imaging tools into
the standard work up and indicating an important confounder of
standard minimal residual disease diagnostics
in Multiple Myeloma.
