management of patients with first relapse non igm … · management of patients with first relapse...
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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
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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