Genomic profiles and clinical outcomes of de novo blastoid/pleomorphic MCL are distinct from those of transformed MCL

Author:

Jain Preetesh12ORCID,Zhang Shaojun3ORCID,Kanagal-Shamanna Rashmi4ORCID,Ok Chi Young4,Nomie Krystle1,Gonzalez Graciela Nogueras5,Gonzalez-Pagan Omarya2,Hill Holly A.1ORCID,Lee Hun Ju1,Fayad Luis1,Westin Jason1ORCID,Nastoupil Loretta1,Hagemeister Frederick1,Chen Wendy1,Oriabure Onyeka1,Badillo Maria1,Jiang Changying1,Yixin Yao1,Li Shaoying3ORCID,Tang Guilin3,Yin C. Cameron3,Patel Keyur P.3ORCID,Medeiros Leonard Jeffrey3ORCID,Nair Ranjit1,Ahmed Sairah1,Iyer Swaminathan P.1,Thirumurthi Selvi6,Champlin Richard7ORCID,Xu Guofan8,Tinsu Pan9,Santos David10,Wang Ruiping3,Han Guangchun3,Zhang Jianhua3,Song Xingzhi3,Neelapu Sattva1ORCID,Romaguera Jorge1,Futreal Andy3,Flowers Christopher1,Fowler Nathan1,Wang Linghua3ORCID,Wang Michael L.17ORCID

Affiliation:

1. Department of Lymphoma and Myeloma,

2. Division of Cancer Medicine,

3. Department of Genomic Medicine,

4. Department of Hematopathology,

5. Department of Biostatistics,

6. Department of Gastroenterology,

7. Department of Stem Cell Transplantation and Cellular Therapy,

8. Department of Nuclear Medicine,

9. Department of Imaging Physics, and

10. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Abstract

Abstract Blastoid and pleomorphic mantle cell lymphomas (MCLs) are variants of aggressive histology MCL (AH-MCL). AH-MCL can arise de novo (AH-DN) or transform from prior classic variant MCL (AH-t). This study is the first integrated analysis of clinical and genomic characteristics of AH-MCL. Patient characteristics were collected from diagnosis (AH-DN) and at transformation (AH-t). Survival after initial diagnosis (AH-DN) and after transformation (AH-t) was calculated. Regression tree analysis was performed to evaluate prognostic variables and in univariate and multivariate analyses for survival. Whole-exome sequencing was performed in evaluable biopsy specimens. We identified 183 patients with AH-MCL (108 were AH-DN, and 75 were AH-t; 152 were blastoid, and 31 were pleomorphic). Median survival was 33 months (48 and 14 months for AH-DN and AH-t, respectively; P = .001). Factors associated with inferior survival were age (≥72 years), AH-t category, Ki-67 ≥50% and poor performance status. AH-t had a significantly higher degree of aneuploidy compared with AH-DN. Transformed MCL patients exhibited KMT2B mutations. AH-MCL patients with Ki-67 ≥50% had exclusive mutations in CCND1, NOTCH1, TP53, SPEN, SMARCA4, RANBP2, KMT2C, NOTCH2, NOTCH3, and NSD2 compared with low Ki-67 (<50%). AH-t patients have poor outcomes and distinct genomic profile. This is the first study to report that AH-MCL patients with high Ki-67 (≥50%) exhibit a distinct mutation profile and very poor survival.

Publisher

American Society of Hematology

Subject

Hematology

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