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3066 Outcomes of Patients with t(11;14) Multiple Myeloma: An International Myeloma Working Group Multicenter Study

Program: Oral and Poster Abstracts
Session: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II
Hematology Disease Topics & Pathways:
Diseases
Sunday, December 8, 2019, 6:00 PM-8:00 PM
Hall B, Level 2 (Orange County Convention Center)

Shaji K. Kumar, MD1, Jin Lu, MD/Prof2, Yang Terry Liu, PhD3*, Max Bittrich, MD4*, Juan Du, MD5*, Hartmut Goldschmidt, MD6, Charalampia Kyriakou, MD, PhD7, Donna E Reece, MD8, Kihyun Kim, MD, PhD9, Maria-Victoria Mateos10, Veronica Gonzalez De La Calle, MD, PhD11*, Wenming Chen, MD12*, Heinz Ludwig, MD13, Giampaolo Merlini, MD14, Silvia Mangiacavalli15*, Meletios A. Dimopoulos, MD16, Eftathios Kastritis17*, Chang-Ki Min, MD, PhD18*, Graca Esteves19*, Andrew J. Yee, MD20, Noopur S. Raje, MD20, Emily Rosta21*, Anja Haltner22*, Chris Cameron23* and Brian G.M. Durie, MD24

1Mayo Clinic, Rochester, MN
2Peking University People's Hospital, National Clinical Research Center for Hematologic Disease, Beijing, China
3Peking University, Beijing, CHN
4Department of Internal Medicine II, University Hospital Wuerzburg, Wuerzburg, Germany
5Department of Hematology, Myeloma & Lymphoma Center, Shanghai Changzheng Hospital, Shanghai, China
6Heidelberg University Hospital, Department of Internal Medicine V, Heidelberg, Germany
7Department of Haematology, University College London Hospitals NHS Foundation Trusts, London, United Kingdom
8Department of Medical Oncology and Hematology, Princess Margaret Hospital, Toronto, ON, Canada
9Division of Hematology-Oncology, Department of Internal Medicine, Sungkyunkwan Univ. Sch. of Med. Samsung Medical Center, Seoul, Korea, Republic of (South)
10Institute of Cancer Molecular and Cellular Biology, University Hospital of Salamanca, Salamanca, Spain
11Departamento de Hematología, Hospital Universitario de Salamanca (HUSAL), IBSAL, IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain
12Department of Hematology, Beijing Chao Yang Hospital, Capital Medical University, Beijing, China
13Wilhelminenspital, Vienna, Austria
14Department of Molecular Medicine, Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy
15Hematology Division, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy
16National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
17Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, ATHENS, Greece
18Division of Lymphoma-Myeloma,, Catholic Hematology Hospital, Seoul St. Mary’s Hematology Hospital College of Medicine, The Catholic University of Korea, Seoul, Korea, Republic of (South)
19Centro Hospitalar Lisboa Norte, Lisboa, PRT
20Massachusetts General Hospital Cancer Center, Boston, MA
21Cornerstone Research Group, Inc., Sydney, NS, Canada
22C, Sydney, NS, Canada
23Cornerstone Research Group, Sydney, NS, Canada
24Cedars Sinai Cancer Center, Los Angeles, CA

Background: Multiple myeloma (MM) is a heterogeneous disease with varying survival outcomes depending on the presence of certain genetic abnormalities. Common abnormalities include trisomies, translocations involving the chromosome 14, and amplifications or deletions of chromosomes 1, 13, and 17. t(11;14), occurring in 15% of patients with myeloma, had been considered a standard risk abnormality, but recent data suggest inferior outcome. This is important as new therapeutic options such as the BCL-2 inhibitor venetoclax has been shown to be particularly effective in t(11;14) patients.

Methods: This was a multicenter study to identify the outcomes of patients with t(11;14), using a retrospectively assembled cohort. Patients with MM diagnosed between 2005 and 2015 with t(11;14) identified on FISH performed within six months of diagnosis, and with treatment details available and if alive, a minimum of 12 months of follow up, were enrolled.

Results: The current analysis includes 1216 patients; median age of 62.56 years; 58.7% male. The median follow-up from diagnosis for the entire cohort was 51.9 months; 69.1% of the patients were alive at the last follow up. ISS stage distribution included: Stage I (35.7%), Stage II (34.0%) and Stage III (15.1%), data was missing for the rest. The distribution of concurrent FISH abnormalities included: trisomies (3.5%), del 13q (13.3%), 1q amp (8.8%), and del 17p or monosomy 17 (5.8%). Initial regimen included: 27.2% had an immunomodulatory (IMiD), 45.9% had a proteasome inhibitor (PI), 17.7% had both, and 9.0% had no novel agent. The drug classes by line of therapy are shown in Table 1. An early stem cell transplant (defined as within 12 months of start of first line treatment) was used in 49.4% of patients. The median time to next treatment (TTNT) after starting initial treatment was 26.6 (95% CI: 23.9 to 29.2) months. The median overall survival (OS) from diagnosis for the entire cohort was 95.1 (95% CI: 85.9 to 105.9) months; 4-year estimates for those diagnosed from January 2005 to December 2009, and from January 2010 to December 2014 were 77.5% and 78.6%, respectively. The median OS for those with any one high risk FISH lesion (del 17p/ 1q amp) was 67.5 (55.2, 97.1) versus 101.7 (89.7, 107.3) months. Patients with early SCT (within 12 months of diagnosis) had better OS: 108.3 (103.8, 133.0) vs. 69.8 (61.5, 80.3) months.

Conclusion: Patients with t(11;14) without high risk FISH abnormalities have an excellent survival. Patients receiving a PI + IMiD combination and those receiving autologous SCT as part of initial therapy had best survival. Though numbers are limited, patients in the later lines receiving newer drugs such as venetoclax and daratumumab had high response rates and durable responses.

Disclosures: Kumar: Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding. Bittrich: Celgene: Other: Travel Funding, Research Funding; Else Kröner Fresenius Foundation: Research Funding; Otsuka Pharmaceuticals Europe: Other: N/A; SANOFI Aventis: Membership on an entity's Board of Directors or advisory committees, N/A, Research Funding; University Hospital Wuerzburg: Employment; Bristol Myers Squibb: Research Funding; Pfizer: Other: Travel Funding; AMGEN: Other: Travel Funding; JAZZ Pharmaceuticals: Other: Travel Funding; Wilhelm Sander Foundation: Research Funding; German Research Foundation (DFG): Other: N/A; University of Würzburg: Other: N/A. Goldschmidt: Mundipharma: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; John-Hopkins University: Research Funding; Dietmar-Hopp-Stiftung: Research Funding; Janssen: Consultancy, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MSD: Research Funding; Molecular Partners: Research Funding; John-Hopkins University: Research Funding; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Honoraria, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Reece: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Merck: Research Funding. Mateos: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: 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; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmamar: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria; EDO: Membership on an entity's Board of Directors or advisory committees. Ludwig: Celgene: Speakers Bureau; Amgen: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; PharmaMar: Consultancy; Janssen: Speakers Bureau; BMS: Speakers Bureau. Mangiacavalli: celgene: Consultancy; Amgen: Consultancy; Janssen cilag: Consultancy. Dimopoulos: Sanofi Oncology: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Research Funding; BMS: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria. Kastritis: Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Honoraria; Prothena: Honoraria; Genesis: Honoraria. Yee: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Karyopharm: Consultancy; Adaptive: Consultancy. Raje: Amgen Inc.: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene Corporation: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Rosta: Cornerstone Research Group: Employment. Haltner: Cornerstone Research Group: Employment. Cameron: Cornerstone Research Group: Employment, Equity Ownership. Durie: Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy.

*signifies non-member of ASH