"Como eu sei se o meu paciente está respondendo? Porque isso é critico?”

Breno Moreno de GusmãoBP, a Beneficência Portuguesa de São Paulo

Hospital Santa Lúcia - Brasilia

Diagnostico diferencial

Discrepancies between the percentage of plasma cells in bone marrowaspiration and BM biopsy: Impact on the revised IMWG diagnostic criteria of

multiple myeloma

Blood Cancer Journal (2017) 7, e530

IgA Kappa/IgA Lambda Heavy/Light Chain Assessment in theManagement of Patients With IgA Myeloma

Cancer December 15, 2014

ATENÇÃO:-IgA-Hipogamma-No secretor

Dosagem de IgCadeias leve K/LCadeia pesada

Recommendations on further examinations at diagnosis, for response assessment, during follow-up and at relapse.

haematologica | 2018; 103(11)

Current Treatment Paradigm for Active Myeloma

Induction

Induction Followed by Continuous Maintenance Therapy

Consolidation MaintenanceSC

T El

igib

leSC

T In

elig

ible

Dia

gno

sis

and

Ris

k St

rati

fica

tio

n

Tumor Burden

Managing Relapse

Slide credit: clinicaloptions.com

MIELOMA IGG

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

Diag. 1er ciclo 2º ciclo 3º ciclo

Ig G mg/dl

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

Ig G mg/dl

Caelyx

Aférese

TCH

Evolução

Follow-up of multiple myeloma patients according to response and patients’ characteristics

haematologica | 2018; 103(11)

The monitoring intervals are gen- erally shorter for patients with high-risk disease (monthly

follow-up) than for patients with standard-risk disease (every 2 to 3 months).

Eliminação do CM

A) monomeric κ sFLCs; (B) dimeric λ sFLCs; (C) monomeric κ sFLCs with renal failure; (D) IgA and (E) IgG.(Courtesy of N. Evans and M. Chappell).

Follow-up of multiple myeloma patients according to response and patients’ characteristics

haematologica | 2018; 103(11)

The monitoring intervals are gen- erally shorter for patients with high-risk disease (monthly

follow-up) than for patients with standard-risk disease (every 2 to 3 months).

Influence of Pre- and Post-Transplantation Responses on Outcome of Patients MultipleMyeloma: Sequential Improvement of Response and Achievement of Complete Response Are Associated With Longer Survival

Lahuerta et al JCO 2008

DRM Pre-TMO

Fig 2.

(A) Progression-free survival (PFS) and (B) overall survival (OS) from time of minimal

residual disease (MRD) assessment (9 months after study enrollment) per con ventional

response assessment: less than partial response (< PR), partial response (PR), near -complete

response (nCR) and complete response (CR). (C) PFS and (D) OS with MRD ne gativity

(MRD−) status in addition to conventional response criteria.

Lahuerta et al. Page 16

J Clin Oncol. Author manuscript; available in PMC 2017 September 01.

Europe PMC Funders Author Manuscripts Europe PMC Funders Author Manuscripts

Lahuerta et al , JCO 2017

Minimal residual disease monitoring and immune profiling in multiple myelomain elderly patients

Paiva et al , Blood 2016

RVd*†

8 cycles

IMAJEM: Substudy Design of Phase III IFM/DFCI 2009

• Phase III randomized study (N = 134 in IMAJEM analysis)

Pts 65 yrs of age or

younger with symptomatic

NDMM with organ

damage and measurable

disease

(N = 700) RVd*

3 cycles

Lenalidomide

maintenance

12 mosRVd*

2 cycles

consolidation

MEL200

ASCT†

Moreau P, et al. ASH 2015. Abstract 395.

MRI or PET/CT

at diagnosis

MRI or PET/CT

after 3 cycles of RVD

MRI or PET/CT before maintenance

Primary Endpoint Secondary Endpoint Secondary Endpoint

*RVD: bortezomib 1.3 mg/m2 IV on Days 1, 4, 8, 11 + lenalidomide 25 mg on Days 1-14 + dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11, 12.†Included PBSC collection with cyclophosphamide 3 g/m2 + G-CSF after cycle 3.14

IMAJEM Secondary Endpoint: Prognostic Impact After 3 Induction Cycles

• Negative MRI (3% of pts) not predictive of survival • Negative PET/CT (32% of pts) associated with improved PFS, not OS

Moreau P, et al. ASH 2015. Abstract 395.

Pro

ba

bili

ty o

f P

FS

MRI neg

MRI pos

1.0

0.8

0.6

0.4

0.2

0.0

P = .29

61.6%

0 10 20 30

Pro

ba

bili

ty o

f O

S

MRI neg

MRI pos

1.0

0.8

0.6

0.4

0.2

0.0

P = .61

86.1%

0 10 20 30 40

Pro

ba

bili

ty o

f P

FS PET/CT neg

PET/CT pos

1.0

0.8

0.6

0.4

0.2

0.0

P = .04

54.8%

0 10 20 30

Pro

ba

bili

ty o

f O

S

PET/CT neg

PET/CT pos

1.0

0.8

0.6

0.4

0.2

P = .12

81.8%

0 10 20 30 40

78.7%

92.8%

0.0

IMAJEM Secondary Endpoint: Prognostic Impact Before Maintenance

• Negative MRI (11% of pts) not predictive of survival • Negative PET/CT (62% of pts) associated with improved PFS, OS

Pro

ba

bili

ty o

f P

FS

MRI neg

MRI pos

1.0

0.8

0.6

0.4

0.2

0.0

P = .30

60.7%

0 10 20 30

Pro

ba

bili

ty o

f O

S

MRI neg

MRI pos

1.0

0.8

0.6

0.4

0.2

0.0

P = .30

85.1%

0 10 20 30 40

Pro

ba

bili

ty o

f P

FS

PET/CT neg

PET/CT pos

1.0

0.8

0.6

0.4

0.2

0.0

P < 0.00151.6%

0 10 20 30

Pro

ba

bili

ty o

f O

S

PET/CT neg

PET/CT pos

1.0

0.8

0.6

0.4

0.2

P = .003

69.9%

0 10 20 30 40

69%

94.6%

0.0

83.9%

Moreau P, et al. ASH 2015. Abstract 395.

IMAJEM: Premaintenance PET/CT and MRD Negativity as Predictor for PFS

• Additional data assessed MRD status (by flow cytometry) on 86 of the 134 pts in this study[1]

1. Avet-Loiseau H, et al. ASH 2015. Abstract 730.

2. Moreau P, et al. ASH 2015. Abstract 395..

Patients, n PET/CT Positive PET/CT Negative

MRD positive 11 20

MRD negative 14 41

Fisher exact test, P = .33; McNemmar test, P = .39

PET/CT/MRD neg (n = 41)

Others (n = 45)

Pro

babili

ty o

f P

FS

1.0

0.8

0.6

0.4

0.2

0.0

P = .02

54.5%

89.6%

350 5 10 15 20 25 30

Obrigado pela atenção !

Breno Moreno de GusmãoBP, a Beneficência Portuguesa de São Paulo

Hospital Santa Lúcia – Brasilia

bgusmao@hotmail.com

@morenodegusmao