-Author name in bold denotes the presenting author
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Clinically Relevant Abstract denotes an abstract that is clinically relevant.

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1881 Light Chain Escape in Multiple MyelomaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster I
Hematology Disease Topics & Pathways:
Diseases, multiple myeloma, Plasma Cell Disorders, Lymphoid Malignancies
Saturday, December 1, 2018, 6:15 PM-8:15 PM
Hall GH (San Diego Convention Center)

Thomas Dejoie1*, Guillemette Fouquet2*, Cyrille Hulin, MD3*, Murielle Roussel, MD4*, Benjamin Hebraud4*, Lionel Karlin, MD5*, Brigitte Kolb, MD6*, Carla Araujo, MD7*, Nathalie Meuleman, PhD, MD8*, Mourad Tiab, MD9*, Jean Valère Malfuson, MD10*, Pascal Bourquard, MD11*, Pascal Lenain, MD12*, Arnaud Jaccard, MD, PhD13*, Karim Belhadj14*, Gérard Lepeu, MD15*, Marie Lorraine Chretien, MD16*, Denis Caillot17*, Jean Fontan, MD18*, Philippe Rodon, MD19, Anna Schmitt20*, Laurent Voillat, MD21*, Sophie Cereja, MD22*, Brigitte Pegourie, MD23*, Frederique Kuhnowski, MD24*, Sophie Rigaudeau, MD25*, Olivier Decaux, MD26*, Catherine Humbrecht-Kraut, MD27*, Jamilé Frayfer, MD28*, Laurent Garderet29, Damien Roos-Weil, MD30*, Jean Claude Eisenmann, MD31*, Veronique Dorvaux, MD32*, Eric G. Voog, MD33*, Claire Mathiot, MD34*, Jean-Paul Fermand, MD35*, Thierry Facon36*, Hervé Avet-Loiseau, MD PhD37*, Jean Luc Harousseau, MD38, Philippe Moreau39*, Michel Attal, MD, PhD40 and Xavier Leleu, MD, PhD41

1university hospital, Nantes, France
2Institut Imagine, Inserm U1163 - CNRS ERL8254, Hôpital Necker, Paris, France
3Hopital De Haut Leveque, Pessac, France
4Institut Universitaire du Cancer and University Hospital, Toulouse, France
5Department of Hematology, Hospices Civils de Lyon, CHU Lyon Sud, University Claude Bernard Lyon 1, Pierre Benite, France
6Hopital Robert Debre, Reims Cedex, France
7Centre Hospitalier de la Cote Basque, Bayonne, France
8Institut Jules Bordet, Brussels, BEL
9CH la Roche Sur Yon, La Roche Sur Yon Cedex 9, FRA
10Dept. of Hematology, Hopital Percy, Clamart, France
11Hôpital Caremeau, Nimes Cedex 9, FRA
12Hematology department, Centre Henri Becquerel, Rouen, France
13Hematology Department, CHU Limoges, Limoges, France
14Centre Hospitalier Universitaire Henri Mondor, Créteil, France
15Centre hospitalier d'Avignon, Avignon, France
16Dijon University Hospital Center, Dijon, France
17Hôpital du Bocage, CHU de Dijon, Dijon, France
18Jean Minjoz Hôpital, Besancon, France
19Centre Hospitalier de Périgueux, Périgueux, France
20Institut Bergonie, Bordeaux, France
21Hematology Department, Hôpital William Morey, Chalon sur Saone, France
22Hopital Avicenne, Bobigny, FRA
23Department of Hematology, Centre Hospitalier Universitaire (CHU) Grenoble, Grenoble, France
24Hematology Department, Curie Institute, Paris, France
25Service Hematologie, CHU Andre Mignot, Versailles, France
26Internal Medicine Department, Rennes, FRA
27Centre Hospitalier de Colmar, Colmar, France
28Department of Hematology, Hospital Saint Faron, MEAUX, France
29Service d’Hématologie et Thérapie Cellulaire, Hopital Saint Antoine, Paris, France
30Hematology Department,Sorbonne Universités, UPMC Univ Paris 06, GRC-11, Hopital Pitié-Salpêtrière, Paris, France
31Centre Hospitalier de Mulhouse, MULHOUSE, FRA
32Centre Hospitalier Régional de Mercy Metz-Thionville, Ars Laquenexy, FRA
33Clinique Victor Hugo, Le Mans, FRA
34Institut Curie, Paris, FRA
35Département d'Immuno-Hématologie, APHP, Paris, FRA
36Regional University Hospital of Lille, Lille, France
37Unité de Génomique du Myélome, IUC-Oncopole, Toulouse, France
38CHU de Nantes, Nantes, France
39University Hospital Hôtel-Dieu, Nantes, France
40Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
41Service D'Hématologie Et Thérapie Cellulaire, Poitiers, FRA

Background. Progression by serum free light chain (sFLC) test without or preceding progression with intact immunoglobulin (Ig) is called light chain escape. This event alone is not considered a progression for patients with Multiple Myeloma (MM) according to International guidelines, although it is often considered a progression in real life and by clinical trials’ investigators. We therefore sought to determine whether light chain escape would be a predictor of relapse and thus question a possible need to modify the current criteria for progression according to the International Myeloma Working Group (IMWG).

Material and method. We have reviewed 325 (323 for analysis) patients that presented with a progression in the IFM/DFCI2009 phase 3 study (Attal et al. NEJM 2017). Among these 323 patients, 260 had initial tumor bulk measurement with intact Ig by serum protein electrophoresis test (SPEP; Ig ≥ 10 g/L) and 63 light chain MM (Ig < 10 g/L) measured using urine protein electrophoresis (UPEP). All progressions were validated in the central laboratory of CHU de Nantes (Dr T. Dejoie) and followed IMWG recommendations. sFLC increase was determined by absolute increase ≥ 100 mg/L and ≥ 25% from nadir value of the difference between involved and uninvolved FLC (ΔiFLC). Light chain escape was defined as sFLC increase without progression by SPEP (Ig increase ≥ 5 g/L and ≥ 25%) or UPEP (increase ≥ 200 mg/24h and ≥ 25%).

Results. Among the 260 patients with intact Ig at diagnosis, 3 (1.15%) patients presented a light chain escape: progression by sFLC test without progression by SPEP. In parallel, 228 patients (87.7%) progressed by SPEP, of whom 18/228 (6.25%) showed a sFLC increase preceding the increase of intact Ig, with a median delay of 63 days.

Among the 63 light chain MM, 6 (9.5%) patients presented a light chain escape: progression by sFLC test without progression by UPEP. Interestingly, 6 other patients (9.5%) progressed by SPEP even though Ig was < 10 g/L at diagnosis. Of the remaining 46 patients, 38 (60.3%) showed sFLC increase before progression by UPEP. Finally, 8 patients (12.7%) progressed but with intact Ig pauci-secreting MM meeting none of the M spike based progression criteria.

Median time from iFLC nadir to ΔiFLC ≥ 100 mg/L was 280 days for light chain MM, 496 days for intact Ig MM, and 651 days for light chain escape. Median time from ΔiFLC ≥ 100 mg/L to follow-up visit to assess progression was 402 days light chain MM, 536 days for intact Ig MM, and 713 days for light chain escape.

Overall, 9 (3%) patients had true light chain escape with progression by sFLC test without any other progression criteria. In parallel, in 56 (17%) patients, sFLC increase preceded progression to MM by standard test (SPEP or UPEP). Still the vast majority of patients had a regular relapse using the standard markers for progression.

Conclusion. Based on a large study of patients treated into a phase 3 clinical trial with centralized assessment of response and progression, we showed that 20% of patients had progression by sFLC without meeting standard progression markers, of whom 3% had true light chain escape and 17% early light chain increase. Even though true light chain escape seems to be a rare phenomenon, analysis of sFLC test could help to avoid delayed or missed diagnosis of progression in 20% of patients in this clinical trial. This data should be confirmed in another database to assess whether a modification in the progression criteria in MM International guidelines should be proposed.

Disclosures: Hulin: Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Roussel: Takeda: Other: Advisory Board; Celgene: Other: Advisory Board; Amgen: Other: Advisory Board; Janssen: Other: Advisory Board. Hebraud: Amgen: Consultancy; Janssen: Consultancy, Other: Lecture fees; travel and accommodation for congress, Research Funding; Sanofi: Consultancy; Takeda: Consultancy; Celgene: Consultancy, Other: Lecture fees, Research Funding. Karlin: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel support; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Belhadj: Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Decaux: Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Garderet: Amgen: Consultancy; Takeda: Consultancy; Celgene: Consultancy. Facon: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Avet-Loiseau: Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Moreau: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Attal: Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Janseen: Consultancy, Research Funding; Sanofi: Consultancy. Leleu: Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH