Secondary plasma cell leukaemia treated with single agent venetoclax

Glavey, Siobhán; Flanagan, Lyndsey; Bleach, Rachel; Kelly, Claire; Quinn, John; Chonghaile, Tríona Ní; Murphy, Philip

doi:10.1111/bjh.16858

Cited by 16 publications

(12 citation statements)

References 12 publications

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“…As a consequence, our understanding in the oncogenic mechanisms and the biology leading to the aggressive clinical course of PCL remain elusive. Similarly, the molecular defects of PCL—especially those of the sPCL type- remain inadequately explored, with most of the reported series referring to retrospective studies or case reports, many of which apply conventional cytogenetics that may underestimate some of the major chromosomal aberrations detected by more sensitive approaches, such as 17p deletions and/or some of the 14q32 rearrangements [ 15 , 25 , 26 , 27 , 28 , 29 ]. In the present study, we have prospectively evaluated a broad panel of abnormalities highlighting particular dissimilarities between NDMM, pPCL and sPCL and further displayed clonal evolutionary patterns associated with the leukemic transformation of primary MM to sPCL.…”

Section: Discussionmentioning

confidence: 99%

The Cytogenetic Profile of Primary and Secondary Plasma Cell Leukemia: Etiopathogenetic Perspectives, Prognostic Impact and Clinical Relevance to Newly Diagnosed Multiple Myeloma with Differential Circulating Clonal Plasma Cells

et al. 2022

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Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia that may appear as de-novo leukemia (pPCL) or on the basis of a pre-existing multiple myeloma (MM), called secondary plasma cell leukemia (sPCL). In this prospective study, we have applied a broad panel of FISH probes in 965 newly diagnosed MM (NDMM) and 44 PCL cases of both types to reveal the particular cytogenetic differences among the three plasma cell dyscrasias. In order to evaluate the frequency and patterns of clonal evolution, the same FISH panel was applied both at diagnosis and at the time of first relapse for 81 relapsed MM patients and both at MM diagnosis and during sPCL transformation for the 19 sPCL cases described here. pPCL was characterized by frequent MYC translocations and t(11;14) with a 11q13 breakpoint centered on the MYEOV gene, not commonly seen in MM. sPCL had a higher number of FISH abnormalities and was strongly associated with the presence of del(17p13), either acquired at the initial MM stage or as a newly acquired lesion upon leukemogenesis in the context of the apparent clonal evolution observed in sPCL. In clinical terms, sPCL showed a shorter overall survival than pPCL with either standard or high-risk (t(4;14) and/or t(14;16) and/or del(17p13) and/or ≥3 concomitant aberrations) abnormalities (median 5 months vs. 21 and 11 months respectively, p < 0.001), suggesting a prognostic stratification based on cytogenetic background. These observations proved relevant in the NDMM setting, where higher levels of circulating plasma cells (CPCs) were strongly associated with high-risk cytogenetics (median frequency of CPCs: 0.11% of peripheral blood nucleated cells for high-risk vs. 0.007% for standard-risk NDMM, p < 0.0001). Most importantly, the combined evaluation of CPCs (higher or lower than a cut-off of 0.03%), together with patients’ cytogenetic status, could be used for an improved prognostic stratification of NDMM patients.

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Section: Discussionmentioning

confidence: 99%

The Cytogenetic Profile of Primary and Secondary Plasma Cell Leukemia: Etiopathogenetic Perspectives, Prognostic Impact and Clinical Relevance to Newly Diagnosed Multiple Myeloma with Differential Circulating Clonal Plasma Cells

et al. 2022

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“…There is very limited data on therapeutic options for patients with sPCL, due to the lack of prospective clinical trials specific for patients with PCL. However, our recent report is a single case study demonstrating a rapid and deep response in one patient with ventoclax [44]. However, further data is needed to support the use of this agent in larger numbers of PCL patients.…”

Section: Development Of Bh3 Mimeticsmentioning

confidence: 78%

“…In our recent publication entitled "Secondary plasma cell leukaemia treated with single agent venetoclax" [44], we assessed if precision functional profiling correctly identified Bcl-2 dependence in MM cells (Figure 2). Primary myeloma patient bone marrow samples were collected following written informed consent and with local ethics committee approval.…”

Section: Methodsmentioning

confidence: 99%

Functional Precision Profiling: The Way Forward for Personalized Medicine

2021

Journal of Clinical Haematology

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“…Our study had a disproportionately high number of plasma cell leukemia cases. Although case reports of successful venetoclax treatment of primary (26)(27)(28) and secondary (29,30) plasma cell leukemia have been published, our study presents the highest number of cases available in literature so far. Plasma cell leukemia confers a prognosis significantly worse than MM itself: OS in secondary PCL is reported to be 1-4 months (21,31), largely unchanged in recent years despite the introduction of novel agents.…”

Section: Discussionmentioning

confidence: 93%

“…Notably, the prevalence of t (11; 14) is very high in two related plasma cell disorders: almost half of all patients with plasma cell leukemia or AL amyloidosis have this translocation (20,21), venetoclax use may therefore have a great impact in these patient groups. Case reports so far have described promising results in both AL amyloidosis (22)(23)(24)(25) and PCL (26)(27)(28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

Targeted Venetoclax Therapy in t(11;14) Multiple Myeloma: Real World Data From Seven Hungarian Centers

Szita¹,

Mikala²,

Kozma³

et al. 2022

Pathol. Oncol. Res.

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Despite the introduction of novel agents, multiple myeloma remains incurable for most patients, necessitating further therapeutic options. Venetoclax, a selective BCL-2 inhibitor, had shown promising results in patients with translocation t(11;14), but questions remain open about its optimal use. We have contacted all Hungarian haematology centers for their experience treating t(11;14) myeloma patients with venetoclax. 58 patients were reported. 37 received venetoclax in the relapsed/refractory setting with few or no other therapeutic options available. 21 patients started venetoclax as salvage after failing to achieve satisfactory response to first line therapy. In the relapsed/refractory setting objective response rate (ORR) was 94%, median progression-free survival (PFS) 10.0 months and median overall survival (OS) 14.6 months. In reinduction patients, ORR was 100%, median PFS and OS were not reached. Importantly, we found no adverse effect of high risk features such as deletion 17p or renal failure, in fact renal failure ameliorated in 42% of the cases, including three patients who became dialysis independent. Our study also reports the highest number of plasma cell leukemia cases successfully treated with venetoclax published in literature, with refractory plasma cell leukemia patients achieving a median PFS of 10.0 and a median OS of 12.2 months.

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Secondary plasma cell leukaemia treated with single agent venetoclax

Cited by 16 publications

References 12 publications

The Cytogenetic Profile of Primary and Secondary Plasma Cell Leukemia: Etiopathogenetic Perspectives, Prognostic Impact and Clinical Relevance to Newly Diagnosed Multiple Myeloma with Differential Circulating Clonal Plasma Cells

The Cytogenetic Profile of Primary and Secondary Plasma Cell Leukemia: Etiopathogenetic Perspectives, Prognostic Impact and Clinical Relevance to Newly Diagnosed Multiple Myeloma with Differential Circulating Clonal Plasma Cells

Functional Precision Profiling: The Way Forward for Personalized Medicine

Targeted Venetoclax Therapy in t(11;14) Multiple Myeloma: Real World Data From Seven Hungarian Centers

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