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1853 Time to Improve Bortezomib and Lenalidomide Lines of Therapy

Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Saturday, December 9, 2017, 5:30 PM-7:30 PM
Bldg A, Lvl 1, Hall A2 (Georgia World Congress Center)

Stephanie Guidez1*, Hélène Demarquette2*, Denis Caillot, MD3*, Artur J. Jurczyszyn, MD, PhD4*, Brigitte Pegourie, MD5*, Marie Lorraine Chretien6*, Charles Lancesseur7*, Lionel Karlin, MD8*, Cristina Joao, MD, PhD, MSc9*, Valentine Richez, MD10*, Laurent Garderet, MD, PhD11, Souhila Ikhlef12*, Bruno Royer, MD13*, Cyrille Hulin, MD14*, Anne Banos, MD15*, Eric Voog, MD16*, Anne-Marie Stoppa, MD17, Lofti Benboubker, MD18*, Niels Abildgaard, M.D.19, Katell Le Du20*, Philippe Moreau21*, Thierry Facon, MD22*, Sonja Zweegman, MD23, Margaret Macro, MD24*, Francesca Marianatal Gay25*, Evangelos Terpos, MD, PhD26 and Xavier Leleu, MD, PhD1

1Department of Oncology-Haematology and Cell Therapy, CHU, Poitiers, INSERM, Inserm CIC 1402, Poitiers, France, Poitiers, France
2Hématologie clinique, CHRU Lille, Lille, France
3Department of Hematology, University Hospital of Dijon, Dijon, France
4Szpital Uniwersytecki W Krakowie, Krakow, POL
5Department of Hematology, Centre Hospitalier Universitaire (CHU) Grenoble, Grenoble, France
6Dijon University Hospital Center, Dijon, France
7Hematology department, CAEN, FRA
8Ch Lyon Sud, Pierre Bénite, France
9University, Lisboa, PRT
10Hematology, CHU Nice, Nice, France
11Service d’Hématologie et Thérapie Cellulaire, Hopital Saint Antoine, Paris, France
12University, Paris, FRA
13Department of Hematology, University Hospital, Amiens, France
14hematology department, university hospital bordeaux, france, bordeaux, UT, France
15Clinical Hematology, Centre Hospitalier de la Cote Basque, Bayonne, France
16Centre hospitalier de le Mans, Le Mans, France
17Institut J Paoli-Calmettes, Marseille, France
18university hospital, tours, France
19Department of Hematology, Odense University Hospital, Odense, Denmark
20Clinique Victor Hugo, Le Mans, FRA
21Department of Hematology, University Hospital Hôtel-Dieu, Nantes, France
22Hôpital Claude Huriez, CHRU Lille, Lille, France
23Department of Hematology, VUMC, Amsterdam, Netherlands
24Haematology Department, Caen University Hospital, Caen, France
25Division of Hematology, University of Torino, Torino, Italy
26Department of Clinical Therapeutics, University of Athens, Drosia, Attiki, Greece

Background.Thalidomide, part of the MPT regimen upfront for eNDMM, e.g. elderly newly diagnosed myeloma, remains one of the most prescribed regimens. It is then often followed by either bortezomib-based at first relapse then lenalidomide-based regimens at the subsequent relapse. This sequence of treatment is challenged by a start with Bortezomib, primarily as VMP as first line, then uniquely followed by lenalidomide-based regimens at first relapse. In the latter, it is likely that patients would not receive thalidomide throughout the disease course of myeloma. We sought to analyse the 2 types of sequence, and demonstrate that patients not exposed to thalidomide upfront, and that were solely exposed to bortezomib-based and lenalidomide-based regimens would have a similar survival than patients exposed to all 3 drugs, e.g. thalidomide, lenalidomide and bortezomib.

Method. A total of 145 patients were recruited in this multicentric study, 46,2% were in the thalidomide upfront exposed arm and 53,8% had never been exposed to thalidomide. Patients were required to be aged ≥65 years, NDMM treated with either thalidomide upfront or never been exposed to thalidomide. If not exposed to thalidomide, the patients were to have received bortezomib upfront and lenalidomide first relapse or vice versa. MPT was given as published. In the non-exposed thalidomide group, all patients had bortezomib upfront, either Vd, VCd or VMP. Lenalidomide and dexamethasone was given as published.

Results. Overall, the median age was 73 years (range, 65 - 85), with 35% aged >75. The M/F ratio was 1.1, 38% were ISS 3, the median b2m was 5.5mg/L, 26% had an ECOG score ≥ 2, 42% had renal insufficiency, 11% had elevated LDH, 8% presence of plasmacytoma, and 14% had adverse FISH (del17p, t(4;14) and or t(14;16)). There was no difference in patients’ characteristics across studied groups, according to exposure or not to thalidomide. With a median follow-up of 5 years, 60% have died overall; 69% in the thalidomide exposed group versus 52% in the thalidomide non-exposed group (p=0.027). The median OS of thalidomide exposed patients was 55.7 months (46;65) versus 44 months (35;53) in the thalidomide non exposed patients (p=0.079). In the thalidomide exposed group, the median PFS of the thalidomide, bortezomib then lenalidomide sequences were 27 months (24;30), 11 months (8;13) and 13 months (10;15). In the thalidomide non-exposed group, the median PFS of bortezomib then lenalidomide lines were 17 months (13;21) and 13 months (6;20). We then studied the survival of patients from onset of first relapse in the thalidomide exposed group, e.g. upon treatment with bortezomib, followed by lenalidomide at subsequent relapse, 22.5 months (10;34) compared to patients in the thalidomide non-exposed group that received bortezomib upfront and lenalidomide at first relapse, 44 months (35;53), p=0.005.

Conclusion. Overall, thalidomide exposed versus non exposed groups had similar OS, while OS was significantly lower in the thalidomide exposed patients at first relapse onset versus in the thalidomide non exposed patients from diagnosis. This data seems to spare the thalidomide but for this it is necessary to optimize the first and second sequences of treatment based on bortezomib and lenalidomide which justifies the use of triplet.

Disclosures: Pegourie: Takeda, Novartis, Janssen, BMS: Consultancy. Garderet: Amgen: Honoraria; Takeda: Honoraria. Royer: JANSSEN: Honoraria, Research Funding. Hulin: JANSSEN: Honoraria. Benboubker: Takeda, Celgene, Janssen, Amgen: Consultancy. Abildgaard: Takeda: Research Funding. Moreau: Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Celgene, Janssen, Takeda, Novartis, Amgen, Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Onyx Pharmaceutical: Consultancy, Honoraria. Facon: Amgen, Celgene: Speakers Bureau. Zweegman: Celgene: Other: advisory board participation, Research Funding; Amgen: Other: advisory board participation; Janssen: Other: advisory board participation, Research Funding; Takeda: Other: advisory board participation, Research Funding. Macro: JANSSEN: Honoraria. Gay: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Mundipharma: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria; Celgene: Honoraria. Terpos: Janssen: Honoraria, Research Funding; Genesis/Celgene: Honoraria, Other: DMC member, Research Funding; Takeda: Honoraria, Other: SC member; Abbvie: Honoraria; Amgen: Honoraria, Other: SC member, Research Funding; BMS: Honoraria; GSK: Honoraria. Leleu: Pierre Fabre: 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; BMS: 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; Amgen: 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; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: 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; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH