MANAGEMENT OF PATIENTS WITH FIRST RELAPSE NON IgM LIGHT CHAIN - - PowerPoint PPT Presentation

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MANAGEMENT OF PATIENTS WITH FIRST RELAPSE NON IgM LIGHT CHAIN AMYLOIDOSIS: A FRENCH MULTICENTRIC RETROSPECTIVE STUDY Camille Villesuzanne 1 , Stephanie Harel MD 2 , Alexis Talbot, MD 2 , Bruno Royer MD 2 , Naelle Lombion MD 2 , Fabien Lebras MD 3

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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

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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-MelDex

r 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 tritherapy recommended

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ISSUE = NO CONSENSUS AT RELAPSE..…

OBJECTIVE

Evaluate therapeutic options used in current practice in France at first relapse, in the management

f patients suffering from systemic non-IgM AL

amyloidosis

MULTICENTRIC RETROSPECTIVE STUDY

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PATIENTS

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

Hematologic response criteria

Initial dFLC > 50 mg/l

CR= negative serum and urine IF and normal K/λ, VGPR= dFLC <40 mg/l PR= dFLC ≥50%

20≤ initial dFLC ≤ 50 mg/l

Low-dFLC response= 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 IKMG May 2019

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108 patients 2003 to 2017 5 hospital centers

RESULTS

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RESULTS

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

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IxaD 2% CyD 2% BendaD 10% MelD 10% Dara D 12% VD 19% RevD 45%

BITHERAPY (n=51)

Others (VTD,CyTD,VMD, RevMD..) 17% VRD 16% CyBorD 67%

TRITHERAPY (n=56)

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50 100 150 50 100

Overall survival at relapse

Months Percent survival

20 40 60 80 100 50 100

Progression Free Survival at relapse

Months Percent survival

GLOBAL RESULTS

Median= 54 {2-127} 9 Median= 13 {1,2-91}

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71% 50% 25% Global hematologic response rate Hematologic response rate ≥ VGPR Organ response

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50 100 150 50 100

Overall survival

Months Percent survival Bitherapy Tritherapy

20 40 60 80 100 50 100

Progression Free Survival

Months Percent survival 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} 10

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31% 68% 19% 30% Bitherapy Tritherapy Hematologic response rate ≥ VGPR Organ response

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50 100 150 50 100

Overall survival

Months Percent survival PI Others

50 100 150 50 100

Progression Free Survival

Months Percent survival 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} 11

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73% 21% 27% 23% PI Others Hematologic response rate ≥ VGPR Organ response

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50 100 150 50 100

Overall survival

Months Percent survival IMIDs Other

50 100 150 50 100

Progression Free Survival

Months Percent survival 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} 12

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26% 63% 31% 22% IMIDs Others Hematologic response rate ≥ VGPR Organ response

50% of organ response in IMIDs based treatment was tritherapy in association with PI ++

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50 100 150 50 100

Progression Free Survival

Months Percent survival RD VRD

RD or VRD

p=0,007 Median= 11 ({2-126} Median= 18,7 {5-91} 13

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17% 67% 21% 55% RD (N=23) VRD (N=9) Hematologic response rate ≥ VGPR Organ response

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20 40 60 80 50 100

PFS PI First line

Months Percent survival

20 40 60 80 100 50 100

PFS PI Second line

Months Percent survival

RE-TREATEMENT WITH PI (n=22)

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

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20 40 60 80 100 50 100

Overall survival

Months Percent survival Bitherapy Tritherapy

20 40 60 80 50 100

Progression Free Survival

Months Percent survival Bitherapy Tritherapy

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

15 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

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20 40 60 80 100 50 100

Overall survival

Months Percent survival PI Others

20 40 60 80 50 100

Progression Free Survival

Months Percent survival PI Others

16 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% severe toxicity

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

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CONCLUSION

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

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?

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ACKNOWLEDGEMENTS

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