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1510 Survival Trends over 18 Years of Patients with Multiple Myeloma Harboring Del(17p) and/or t(4;14): A Retrospective Real-World Study

Program: Oral and Poster Abstracts
Session: 731. Clinical Autologous Transplantation: Results: Poster I
Hematology Disease Topics & Pathways:
multiple myeloma, therapy sequence, Adult, Diseases, Non-Biological, Therapies, Combinations, chemotherapy, Plasma Cell Disorders, Lymphoid Malignancies, Study Population, Clinically relevant
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Thomas Chalopin1*, Nicolas Vallet, MD1*, Marlene Ochmann, MD2*, Mourad Tiab3*, Pascal Godmer4*, Carole Barin5*, Olivier Theisen, MD6*, Olivier Herault, MD, PhD7,8, Emmanuel Gyan, MD, PhD1,7, Lotfi Benboubker, MD1*, Philippe Moreau9,10*, Herve Avet-Loiseau11 and Cyrille Touzeau9,12,13*

1Department of Hematology and Cellular Therapy, Tours University Hospital, UMR CNRS, François Rabelais University, Tours, France
2Hospital of Orleans, Hematology department, Orleans, France
3CH la Roche Sur Yon, La Roche Sur Yon Cedex 9, France
4Clinical Hematology, Centre Hospitalier Bretagne Atlantique, Vannes, France
5Centre Hospitalier universitaire de Tours, Laboratoire de Cytogénétique, Tours, France
6Hematology Biology, Nantes University Hospital, Nantes, France
7CNRS ERL 7001 LNOx "Leukemic Niche & Redox Metabolism", Tours, France
8Service d'Hématologie Biologique, Centre Hospitalier Universitaire, Tours, France
9CRCINA, INSERM, CNRS, Angers University and Nantes University, Nantes, France
10Department of Hematology, University Hospital of Nantes, Nantes, France
11Unite de Genomique du Myelome, IUC-T Oncopole, Toulouse, France
12Site de Recherche Intégrée sur le Cancer (SIRIC), Imaging and Longitudinal Investigations to Ameliorate Decision-making (ILIAD), INCA-DGOS-Inserm 12558, Nantes, France
13Hematology Clinic, University Hospital Hôtel-Dieu, Nantes, France

Introduction. In multiple myeloma (MM), the presence of translocation t(4;14) and/or 17p deletion, found in around 10 to 15% of the patients, is considered as high-risk feature associated with adverse survival. Despite recent advances in the treatment of MM, t(4;14) and del(17p) are still associated with poor outcome. The aim of this study was to analyze the trends of survival in patients with newly diagnosed MM harboring t(4;14) and or 17p deletion over the past two decades.

Methods. Patients from five French centers with newly-diagnosed MM from 2001 to 2019 and displaying del(17p) and/or t(4;14) were retrospectively included. Cytogenetics abnormalities were detected by interphase fluorescence in situ hybridization (FISH) and del(17p) positivity cut-off was 30%. New agents were defined as: pomalidomide, carfilzomib, ixazomib and anti-CD38 monoclonal antibodies.

Results. 246 patients carrying either t(4;14) (n=106 patients), del(17p) (n=121 patients) or both (n=19 patients) were included. Median age was 64 years (range, 35-91). ISS and R-ISS score were 3 in 88 patients (36%). Eighty-seven patients (35%) were diagnosed in 2001-2010 period, and 159 (65%) in 2011-2019 period. Front-line autologous stem-cell transplantation (ASCT) was performed in 121 (49%) patients. Among transplant eligible patients, 112 patients (n=93%) received triplet induction, 78 patients (64%) a consolidation regimen and 15 patients (12%) a maintenance therapy. Double-ASCT was decided in 21 patients (17%). Among transplant ineligible patients, 61 patients (49%) received melphalan-based regimen in first line, 36 (29%) a bortezomib-based and 15 patients (14%) a lenalidomide-based regimen. At any line, 92 patients (37%) received at least one of the new agents with only 12 patients (5%) in frontline therapy.

Median follow-up was 41 months (IQR: 21-69). Median overall survival (OS) was 58.4 months (IQR: 50.1-66.5) for the entire cohort, 55.5 months (IQR: 46.6-78.3) for del(17p), 62.5 months (IQR: 54.2-76.1) for t(4;14) and 48.6 months (18.1-not reached) for patients with both (p=0.2). Median of first progression-free survival (PFS1) was 25.6 months (IQR: 22.2-29.8), with no difference between del(17p), t(4;14) or both (p=0.57). Importantly, no improvement of median OS was observed in patients diagnosed between 2001-2010 in comparison with patients diagnosed between 2011-2019 (63.7 versus 53.2 months, p=0.32). In univariate and multivariate analysis: age (continuous and cut-off 71 years-old) and ASCT significantly were associated with risk of death (HR: 1.03, 1.09 and 0.45, respectively). Median OS of patients eligible to ASCT was 76.1 months (IQR: 62.5-90.3) vs 42.5 months (IQR: 36.8-54.6) for patients not eligible (HR 0.45, 95%CI 0.28-0.0.71; p<0.001). Double-ASCT did not improve significantly OS (75 vs 81.1 months ; p=0.41) and PFS1 (31.6 vs 47.8, p=0.30) compared with single-ASCT.

Conclusion. This large multicenter real-world study confirms that patients with newly diagnosed MM carrying del(17p) and/or t(4;14) remain a therapeutic challenge with no significant overall survival improvement in the past decades despite the use of novel agents. The definition of high-risk MM patients is evolving with incorporation of new markers (i.e chromosome 1 abnormalities, PET-imaging). Minimal-residual disease achievement will also re-defined risk stratification. Nonetheless, the need for innovative approaches such as earlier strategies using new agents or immunotherapy (CAR-T cells, bispecific T-cell engager antibodies) may significantly improve outcomes.

Figure captions

Table 1. Clinical, biological characteristics, treatment and survival of the 246 included patients based on period of diagnosis.

IQR: interquartile range; FISH: fluorescence in situ hybridization; ISS: international score system; LDH: lactate dehydrogenase; ASCT: autologous stem cell transplantation; len: lenalidomide; Poma: pomalidomide; Carfil: carfilzomib; Ixa: ixazomib; mAb: monoclonal antibodies; OS: overall survival

Figure 1. Kaplan-Meier curves for overall survival for the 246 included patients based on period of diagnosis.

Disclosures: Moreau: Novartis: Honoraria; Amgen: Consultancy, Honoraria; Takeda: Honoraria; Sanofi: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria. Touzeau: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

*signifies non-member of ASH