Primary plasma cell leukemias displaying t(11;14) have specific genomic, transcriptional, and clinical features

Abstract

Primary plasma cell leukemia (pPCL) is an aggressive form of multiple myeloma (MM) that has not benefited from recent therapeutic advances in the field. Because very rare and heterogeneous, it remains poorly understood at the molecular level. To address this issue, we performed DNA and RNA sequencing of sorted plasma cells from a large cohort of 90 newly diagnosed pPCL, and compared to MM. We observed that pPCL presents a specific genomic landscape with a high prevalence of t(11;14) (about half) and high-risk genomic features such as del(17p), gain 1q, del(1p32). In addition, pPCL displays a specific transcriptome when compared to MM. We then aimed at specifically characterize pPCL with t(11;14). We observed that this sub-entity displayed significantly fewer adverse cytogenetic abnormalities. This translated into better overall survival when compared to pPCL without t(11;14) (39.2 months vs 17.9 months, p=0.002). Finally, pPCL with t(11;14) displayed a specific transcriptome, including differential expression of BCL2 family members. This study is the largest series of patients with pPCL reported so far.

How do we manage t(11;14) plasma cell disorders with venetoclax?

“…Furthermore, standardized companion diagnostics to test for t(11;14) and BCL2 gene expression are urgently needed for standardization and comparing efficacy across trials. There are emerging data on differential expression of BCL2 family members in transcriptome of t(11;14) primary plasma cell leukaemia, 42 which forms a strong preclinical rationale for testing venetoclax in these patients. Venetoclax has also demonstrated activity in patients with relapsed/refractory Waldenstrom's macroglobulinaemia, with a major response rate and VGPR rate of 81 and 19%, respectively 43 .…”

Primary plasma cell leukemia presented with atypical flower‐like morphology

“…3 Usually it occurs in younger patients, has a more aggressive course and poor outcome. 3 Occasionally, its morphological appearance poses a diagnostic dilemma mimicking flower-cells. 1,2 Similarly to previous reports, our case had unusual flower-like morphology, plasma cell phenotpe, IGH gene rearrangement, unfavorable features including CD56+ and two adverse genetic leasions amplification 1q21, deletion 1p32.…”

How We Manage Newly Diagnosed Multiple Myeloma With Circulating Tumor Cells

“…Interestingly, pPCL with t(11;14) displays significantly fewer adverse cytogenetic abnormalities, compared with pPCL without this translocation, which translates into better OS. 36…”