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1968 11q Gain with t(11;14) or Alone Were Associated with Poor Prognosis in Newly-Diagnosed Multiple Myeloma Patients By SNP-Array Analysis and FISH

Program: Oral and Poster Abstracts
Session: 652. Multiple Myeloma: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, adult, epidemiology, CHIP, Clinical Research, health outcomes research, Genetic Disorders, genomics, bioinformatics, health disparities research, patient-reported outcomes, Diseases, real-world evidence, clinical procedures, computational biology, survivorship, Biological Processes, Technology and Procedures, profiling, Study Population, Human, molecular testing
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Jiao Lu1,2*, Chengcheng Fu1*, Jinlan Pan1*, Zhao Zeng1*, Jingjing Shang3*, Song Jin1*, Lingzhi Yan3*, Zhiyu Zhang1*, Hongying You1*, Xiaolan Shi, MD, PhD1*, Shuang Yan1*, Weiqin Yao1*, Jing Wang3*, Yun Xu4*, Chunxiao Wu1*, Wanhui Yan1*, Hongmiao Shen1*, Yue Huang1*, Xin Xiang4*, Qian Wang1*, Zhi Yan3*, Xingyue Wu1*, Qinrong Wang1*, Lijun Wen, MD5*, Suning Chen1* and Depei Wu1

1National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
2Department of Haematology, Jingjiang People’s Hospital, the Seventh Affiliated Hospital of Yangzhou University, Jingjiang, Jiangsu, China
3National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, Soochow University,, Suzhou, China
4Suzhou Hongci Blood Disease Hospital, Suzhou, China
5National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China

t(11;14) is currently classified as a standard-risk genetic marker for newly diagnosed multiple myeloma (NDMM) patients. But some recent studies have suggested that t(11;14) may be an intermediate-risk marker in multiple myleoma (MM). The clinical significance of t(11;14) in MM is still controversial. Here, using high-resolution single nucleotide polymorphism-based mapping array (SNP-array) analysis and fluorescence in situ hybridization (FISH), the most common gained region of chromosome 11 was identified in 96/611 (15.7%) NDMM patients which located at 11q13.3-q25 (65.7Mb in size and contains 622 genes including CCND1). It demonstrated a statistically significant coexisting with t (11;14) (p<0.001), complex karyotypes (involves at least 6 chromosomes) (p<0.001), high plasma cell ratio in bone marrow (p=0.001) and poor response to VRD (bortezomib, lenalidomide, dexamethasone) treatment (p<0.001), but mutually exclusive with monosome 13, del(13q14), dup1q21 and t (4;14). When exploring the correlation of t(11;14) with genomic copy number variations (CNAs), it was also indicated that t(11;14) was most closely related to 11q gain (39%), while negatively correlated with others including gain of 1q and chromosome 3, 5, 6, 7, 9, 11, 15, 19, loss of 1p, 12p, 14q and chromosome 13 and 22.

With a median follow up time of 22 months, survival analysis of 40 t(11;14) patients, 123 hyperdiploid (HRD) patients showed that 11q gain could have an adverse impact on the progression-free survival (PFS) in both groups. In t(11;14) subgroup, the median PFS (mPFS) were not reached, but PFS at 40 months were 60.9% vs 81.7% with 11q gain vs non-11q gain patients. In HRD subgroup, the mPFS were 23 months vs 49 months with 11q gain vs non-11q gain groups. Autologous hematopoietic stem cell transplantation (ASCT) can significantly improve the PFS of patients with t(11;14) and 11q gain (mPFS for transplant-eligible (TE) vs transplant-ineligible (TIE) patients were not reached vs 9 months, P=0.0067), but not helpful to 11q gain patients without t(11;14) (mPFS for TE vs TIE: 23 months vs 22 months, p=0.2137). Multivariate analysis confirmed that 11q gain was an independent adverse factor to PFS of MM with t(11;14) (Hazard ratio: 11.621, 95% CI: 1.027-131.507; p=0.048; n=37).

Conclusions: Gain of 11q13.3-q25 is a reproducible chromosomal copy number abnormality in NDMM characterized by coexisting with t (11;14), complex karyotypes, higher plasma cell ratio in bone marrow and poor treatment response to VRD. t(11;14) patients with 11q gain had a poorer PFS compared to patients with t(11;14) only, mPFS was only 9 months for TIE patients. t(11;14) with 11q gain NDMM patients needs to be considered as high risk and ASCT could improve patients’ survival.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH