MANAGEMENT OF PATIENTS WITH FIRST RELAPSE NON IgM LIGHT CHAIN AMYLOIDOSIS: A FRENCH

MULTICENTRIC RETROSPECTIVE STUDY

Camille Villesuzanne1, Stephanie Harel MD 2, Alexis Talbot, MD2, Bruno Royer MD2, Naelle Lombion MD2, Fabien Lebras MD3, Nathalie Forgeard2, Mathilde Nouvier MD4, Lionel Karlin MD5, Arnaud Jaccard

MD/PhD1 and Bertrand Arnulf MD/PhD2

1Hematology Department, Limoges University Hospital, Limoges, France; 2Department of Hematology-Immunology, University Hospital APHP, Paris, France; 3Hematology Department, Henri Mondor hospital,

APHP, Créteil, France; 4Nephrology department, Lyon sud hospital, Lyon, France; 4Hematology department, Lyon sud hospital, Lyon, France

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Disclosure of conflict of interest

2IKMG May 2019

• I do not have a relationship with a for-profit and/or a not-for-profit organization to disclose

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• Stage II and IIIA:Upfront Bortezomib-MelDexor CyBorD

• Stade IIIB:✓ Rapid switch if

refractory disease to CyBorD

✓ dFLC measurement once a week

• More rapid reevaluation after 2 cycles.

• If bone marrow plasma cell > 10% = upfront tritherapyrecommended

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ISSUE = NO CONSENSUS AT RELAPSE..…

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OBJECTIVE

Evaluate therapeutic options used in currentpractice in France at first relapse, in the managementof patients suffering from systemic non-IgM ALamyloidosis

MULTICENTRIC RETROSPECTIVE STUDY

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PATIENTS

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FIRST-LINE TREATMENT WITH CONVENTIONAL DOSE CHEMOTHERAPY

HISTOLOGICALLY PROVEN NON-IGM AL AMYLOIDOSIS

FIRST HEMATOLOGIC OR CLINICAL RELAPSE

NO CRITERIA OF SYMPTOMATIC MULTIPLE MYELOMA (IMWG 2016)

INCLUSION CRITERIA

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EFFICACY

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• Hematologic response criteria

Initial dFLC > 50 mg/l

CR= negativeserum and urine

IF and normal K/λ,

VGPR= dFLC <40 mg/l

PR= dFLC ≥50%

20≤ initialdFLC ≤ 50

mg/l

Low-dFLCresponse=

dFLC ≤10 mg/l

• Organ response criteria

NT-proBNP ≥30% ou ≥300 ng/l if initial > 650 ng/l

NYHA ≥2

Proteinuria ≥30% or

< 0,5 g/24h in the absence of reduction in eGFR ≥25%

≥50% in PAL or ≥2 cm of hepatomegaly

Palladini, G. et al. JCO 2012 ; Milani, P. et al. Blood 2017; Dittrich, T. et al. Blood 2017

Gertz, M. A. et al. Am. J. Hematol. 2005; Palladini, G. et al. JCO 2012; Palladini, G. et al. Blood 2014

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108 patients

2003 to 2017

5 hospitalcenters

RESULTS

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RESULTS

MEDIAN TIME FROM DIAGNOSIS TO SECOND LINE THERAPY = 22,5 months {2-169}

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IxaD2%

CyD 2%

BendaD10%

MelD10%

Dara D12%

VD19%

RevD 45%

BITHERAPY (n=51)

Others (VTD,CyTD,VMD,

RevMD..)17%

VRD16%

CyBorD67%

TRITHERAPY (n=56)

0 50 100 1500

50

100

Overall survival at relapse

Months

Perc

en

t su

rviv

al

0 20 40 60 80 1000

50

100

Progression Free Survival at relapse

Months

Perc

en

t su

rviv

al

GLOBAL RESULTS

Median= 54 {2-127}

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Median= 13 {1,2-91}

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71%

50%

25%

Global hematologicresponse rate

Hematologic response rate ≥ VGPR

Organ response

0 50 100 1500

50

100

Overall survival

MonthsP

erc

en

t su

rviv

al

Bitherapy

Tritherapy

0 20 40 60 80 1000

50

100

Progression Free Survival

Months

Perc

en

t su

rviv

al

Bitherapy

Tritherapy

TRITHERAPY OR BITHERAPY

Median= 12 {2-39}

p= 0,001 p= 0,31

Median= 15 {2-91} Median= 63 {3,7-123}

Median= 46 {4-126}

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31%

68%

19%30%

Bitherapy Tritherapy

Hematologic response rate ≥ VGPR Organ response

0 50 100 1500

50

100

Overall survival

MonthsP

erc

en

t su

rviv

al

PI

Others

0 50 100 1500

50

100

Progression Free Survival

Months

Perc

en

t su

rviv

al

PI

Others

PI or OTHER THERAPY

Median= 7,5 { 2-126}

p< 0,0001 p= 0,35

Median= 17 {1,2-90} Median= 63 {3-111}

Median= 46 {52,5-126}

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73%

21%27% 23%

PI Others

Hematologic response rate ≥ VGPR Organ response

0 50 100 1500

50

100

Overall survival

Months

Perc

en

t su

rviv

al

IMIDs

Other

0 50 100 1500

50

100

Progression Free Survival

Months

Perc

en

t su

rviv

al

IMIDs

Other

IMIDS OR OTHER THERAPY

p= 0,08 p= 0,17

Median= 11 {2-126}

Median= 14 {1-76} Median= 51 {3-114}

Median= NA {2,5-NA}

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26%

63%

31%22%

IMIDs Others

Hematologic response rate ≥ VGPR Organ response

50% of organ response in IMIDsbased treatment was

tritherapy in association withPI ++

0 50 100 1500

50

100

Progression Free Survival

Months

Perc

en

t su

rviv

al

RD

VRD

RD or VRD

p=0,007

Median= 11 ({2-126}

Median= 18,7 {5-91}

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17%

67%

21%

55%

RD (N=23) VRD (N=9)

Hematologic response rate ≥ VGPR Organ response

0 20 40 60 800

50

100

PFS PI First line

Months

Perc

en

t su

rviv

al

0 20 40 60 80 1000

50

100

PFS PI Second line

Months

Perc

en

t su

rviv

al

RE-TREATEMENT WITH PI (n=22)

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Median= 23 {4-74} Median= 18,5 {2-91}

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73% 73%

45%36%

First line Second therapy

Hematologic response rate ≥ VGPR Organ response

0 20 40 60 80 1000

50

100

Overall survival

MonthsP

erc

en

t su

rviv

al

Bitherapy

Tritherapy

0 20 40 60 800

50

100

Progression Free Survival

Months

Perc

en

t su

rviv

al

Bitherapy

Tritherapy

eGFR ≤30 ml/min/1,73 m2 (n=26) BITHERAPY OR TRITHERAPY

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Median= 27 {4,9-51}

Median= 63 {8-83}

p= 0,02

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Median= 7 {2,5-32}

Median= 15 {3-63}

p= 0,07

27%

86%

0%

33%

Bitherapy (n=11) Tritherapy (n=15)

Hematologic response rate ≥ VGPR Organ response

0 20 40 60 80 1000

50

100

Overall survival

Months

Perc

en

t su

rviv

al

PI

Others

0 20 40 60 800

50

100

Progression Free Survival

Months

Perc

en

t su

rviv

al

PI

Others

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Median= 63 {8-83}

Median= NA {5-39}

p= 0,4

eGFR ≤30 ml/min/1,73 m2 (n=26) PI OR OTHER THERAPY

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IMIDs= 80% severetoxicity

Median= 15 {3-63}

Median= 7 {2,5-25}

p= 0,07

78%

14%26%

0%

PI based therapy (n=19) Other (n=7)

Hematologic response rate ≥ VGPR Organ response

CONCLUSION

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STATISTICALLY SIGNIFICANT RESULTS FOR PFS IN FAVOUR OF A TRITHERAPY (and OS for eGFR ≤30 ml/min/1,73 m2 patients )

PROTEASOME INHIBITORS SEEM TO BE ESSENTIAL

IMIDS SEEM TO BE TOXIC, PARTICULARLY IN THE MOST SEVERE PATIENTS WITH LOW HEMATOLOGICAL RESPONSE, CONSISTENT WITH THE LITERATURE

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DISCUSSION-PERSPECTIVES

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WHAT IS THE GOOD TIMING TO START SECOND LINE THERAPY?

• Depends on initial organ gravity

• Organ relapse => decrease OS (p=0,02) Hwa et al.Blood 2017

• « high risk dFLC progression »

=> 85% cardiac progression at 6 months, Palladini et al. Blood 2018

MRD, NEW RESPONSE CRITERIA TO TREATMENT?

• MRD + en NGF= decrease PFS and organ response, Palladini et al. Blood 2016

• Impact decision for early retreatment?

WHAT ABOUT MODERN THERAPIES?

• Immunotherapy, NEW PI and BCL2 INHIBITORS

FISH

• CYTOGENETIC Impact for therapeutic decision?IKMG May 2019

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ACKNOWLEDGEMENTS

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