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.