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

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 , Nathalie Forgeard 2 , Mathilde Nouvier MD 4 , Lionel Karlin MD 5 , Arnaud Jaccard MD/PhD 1 and Bertrand Arnulf MD/PhD 2 1 Hematology Department, Limoges University Hospital, Limoges, France; 2 Department of Hematology- Immunology, University Hospital APHP, Paris, France; 3 Hematology Department, Henri Mondor hospital, APHP, Créteil, France; 4 Nephrology department, Lyon sud hospital, Lyon, France; 4 Hematology department, Lyon sud hospital, Lyon, France IKMG May 2019

Disclosure of conflict of interest • I do not have a relationship with a for-profit and/or a not-for-profit organization to disclose IKMG May 2019 2

• Stage II and IIIA: • More rapid Upfront Bortezomib-MelDex reevaluation after or CyBorD 2 cycles. • If bone marrow • Stade IIIB: plasma cell > 10% ✓ Rapid switch if = upfront refractory disease to tritherapy CyBorD recommended ✓ dFLC measurement once a week 3 IKMG May 2019

ISSUE = NO CONSENSUS AT RELAPSE..… OBJECTIVE Evaluate therapeutic options used in current practice in France at first relapse, in the management of patients suffering from systemic non-IgM AL amyloidosis MULTICENTRIC RETROSPECTIVE STUDY IKMG May 2019 4

PATIENTS FIRST-LINE TREATMENT HISTOLOGICALLY PROVEN WITH CONVENTIONAL DOSE NON-IGM AL AMYLOIDOSIS CHEMOTHERAPY INCLUSION CRITERIA NO CRITERIA OF FIRST HEMATOLOGIC OR SYMPTOMATIC MULTIPLE CLINICAL RELAPSE MYELOMA (IMWG 2016) IKMG May 2019 5

EFFICACY • Hematologic response criteria • Organ response criteria  NT-proBNP ≥30% ou ≥300 ng/l if 20≤ initial initial > 650 ng/l Initial dFLC > dFLC ≤ 50  50 mg/l NYHA ≥2 mg/l  Proteinuria ≥30% or CR = negative < 0,5 g/24h in the absence of serum and urine reduction in eGFR ≥25% IF and normal Low-dFLC K/ λ , response = dFLC ≤10 mg/l VGPR = dFLC <40  mg/l ≥50% in PAL or ≥2 cm of hepatomegaly PR =  dFLC ≥50% Palladini, G. et al. JCO 2012 ; Milani, P. et al. Blood Gertz, M. A. et al. Am. J. Hematol. 2005; Palladini, G. et al. 2017; Dittrich, T. et al. Blood 2017 JCO 2012; Palladini, G. et al. Blood 2014 6 IKMG May 2019

RESULTS 5 108 2003 to hospital patients 2017 centers IKMG May 2019 7

RESULTS MEDIAN TIME FROM DIAGNOSIS TO SECOND LINE THERAPY = 22,5 months {2-169} BITHERAPY (n=51) TRITHERAPY (n=56) CyD IxaD 2% 2% Others (VTD,CyTD,VMD, BendaD RevMD..) 10% 17% MelD RevD 10% VRD 45% 16% Dara D CyBorD 12% 67% VD 19% IKMG May 2019 8

GLOBAL RESULTS 71% 50% 25% Global hematologic Hematologic response Organ response response rate rate ≥ VGPR Overall survival at relapse Progression Free Survival at relapse 100 100 Percent survival Percent survival Median= 54 {2-127} Median= 13 {1,2-91} 50 50 0 0 0 50 100 150 0 20 40 60 80 100 IKMG May 2019 9 Months Months

TRITHERAPY OR BITHERAPY Hematologic response rate ≥ VGPR Organ response 68% 31% 30% 19% Bitherapy Tritherapy Progression Free Survival Overall survival Bitherapy Median= 12 {2-39} Median= 46 {4-126} Bitherapy 100 100 Tritherapy Percent survival Median= 63 {3,7-123} Tritherapy Median= 15 {2-91} Percent survival 50 50 p= 0,001 p= 0,31 0 0 0 20 40 60 80 100 0 50 100 150 Months Months IKMG May 2019 10

PI or OTHER THERAPY Hematologic response rate ≥ VGPR Organ response 73% 27% 23% 21% PI Others Progression Free Survival Overall survival Median= 63 {3-111} Median= 17 {1,2-90} PI PI 100 100 Median= 46 {52,5-126} Median= 7,5 { 2-126} Others Others Percent survival Percent survival 50 50 p= 0,35 p< 0,0001 0 0 0 50 100 150 0 50 100 150 Months Months IKMG May 2019 11

IMIDS OR OTHER THERAPY Hematologic response rate ≥ VGPR Organ response 63% 50% of organ response in IMIDs based treatment was 31% 26% tritherapy in association with 22% PI ++ IMIDs Others Progression Free Survival Overall survival Median= NA {2,5-NA} IMIDs Median= 11 {2-126} IMIDs 100 100 Other Median= 51 {3-114} Percent survival Other Percent survival Median= 14 {1-76} 50 50 p= 0,08 p= 0,17 0 0 0 50 100 150 0 50 100 150 Months Months IKMG May 2019 12

RD or VRD Progression Free Survival Hematologic response rate ≥ VGPR Organ response RD Median= 11 ({2-126} 100 67% VRD Percent survival Median= 18,7 {5-91} 55% 50 p=0,007 21% 17% 0 0 50 100 150 RD (N=23) VRD (N=9) Months IKMG May 2019 13

RE-TREATEMENT WITH PI (n=22) Hematologic response rate ≥ VGPR Organ response 73% 73% 45% 36% First line Second therapy PFS PI First line PFS PI Second line 100 100 Percent survival Percent survival Median= 23 {4-74} Median= 18,5 {2-91} 50 50 0 0 0 20 40 60 80 0 20 40 60 80 100 Months Months IKMG May 2019 14

eGFR ≤30 ml/min/1,73 m 2 (n=26) BITHERAPY OR TRITHERAPY Hematologic response rate ≥ VGPR Organ response 86% 33% 27% 0% Bitherapy (n=11) Tritherapy (n=15) Progression Free Survival Overall survival Median= 7 {2,5-32} Median= 27 {4,9-51} Bitherapy Bitherapy 100 100 Median= 15 {3-63} Median= 63 {8-83} Tritherapy Percent survival Tritherapy Percent survival 50 p= 0,02 p= 0,07 50 0 0 0 20 40 60 80 0 20 40 60 80 100 Months Months IKMG May 2019 15

eGFR ≤30 ml/min/1,73 m 2 (n=26) PI OR OTHER THERAPY Hematologic response rate ≥ VGPR Organ response 78% IMIDs= 80% severe toxicity 26% 14% 0% PI based therapy (n=19) Other (n=7) Progression Free Survival Overall survival Median= 15 {3-63} Median= 63 {8-83} PI PI 100 100 Median= 7 {2,5-25} Median= NA {5-39} Others Others Percent survival Percent survival p= 0,07 50 50 p= 0,4 0 0 0 20 40 60 80 0 20 40 60 80 100 Months Months IKMG May 2019 16

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 IKMG May 2019 17

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? IKMG May 2019 18

ACKNOWLEDGEMENTS IKMG May 2019 19