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

Chakraborty, Rajshekhar; Bhutani, Divaya; Lentzsch, Suzanne

doi:10.1111/bjh.18243

Cited by 14 publications

(8 citation statements)

References 45 publications

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“…This phenomenon can also be observed in t(11;14) patients with coexisted high-risk cytogenetic abnormalities. 2 , 22 , 24 , 26 , 42 , 43 Given the promising results of venetoclax, early detection of t(11;14) is necessary to guide the selection of treatments in this subgroup of patients. In addition, other biomarkers, such as BCL-2 expression level and BCL-2/MCL-1 ratio, also harbor significant predictive value for the response to venetoclax.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of venetoclax-based regimens for the treatment of relapsed/refractory multiple myeloma: a systemic review and meta-analysis

Lin

Xing

et al. 2023

Therapeutic Advances in Hematology

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Background: Patients with relapsed/refractory multiple myeloma (RRMM) usually have dismal prognostic outcomes. Venetoclax, a selective inhibitor of antiapoptotic protein B-cell lymphoma-2 (BCL-2), demonstrates antimyeloma activity in plasma cells with t(11;14) or high BCL-2 expression. Objectives: This meta-analysis aimed to investigate the efficacy and safety of venetoclax-based therapy in RRMM. Design: This is a meta-analysis study. Data Sources and Methods: PubMed, Embase, and Cochrane were searched for studies published up to 20 December 2021. Overall response rate (ORR), rate of very good partial response or better (≧VGPR), and complete response (CR) rate were pooled with the random-effects model. Safety was evaluated by the incidences of grade ≧3 adverse events. Subgroup analysis and meta-regression were performed to identify the causes of heterogeneities. All the analyses were conducted by STATA 15.0 software. Results: A total of 14 studies with 713 patients were included for analysis. The pooled ORR, rate of ≧VGPR, and CR for all patients were 59% [95% confidence interval (CI) = 45–71%], 38% (95% CI = 26–51%), and 17% (95% CI = 10–26%), respectively. The median progression-free survival (PFS) ranged from 2.0 months to not reached (NR), and the median overall survival (OS) ranged from 12.0 months to NR. Meta-regression showed that patients treated with more drugs combined or less heavily pretreated had higher response rates. Patients with t(11;14) had superior ORR [relative risk (RR) = 1.47, 95% CI = 1.05–2.07], ≧VGPR (RR = 1.71, 95% CI = 1.12–2.60), CR (RR = 1.86, 95% CI = 1.34–2.57), PFS [hazard ratio (HR) = 0.47, 95% CI = 0.30–0.65], and OS (HR = 0.30, 95% CI = 0.08–0.52) compared with patients without t(11;14). Most grade ≧3 adverse events were hematologic, gastrointestinal, and infectious related and were manageable. Conclusion: Venetoclax-based therapy is an effective and safe option for RRMM patients, especially those with t(11;14).

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of venetoclax-based regimens for the treatment of relapsed/refractory multiple myeloma: a systemic review and meta-analysis

Lin

Xing

et al. 2023

Therapeutic Advances in Hematology

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“…Venetoclax, an oral BCL2 inhibitor, has demonstrated promising efficacy in patients with plasma cell neoplasm harboring t(11;14), which is associated with high BCL2 expression [ 26 ]. Venetoclax is included as a treatment option for relapsed/refractory t(11;14) plasma cell neoplasms in National Comprehensive Cancer Network (NCCN) guidelines, but no country has approved venetoclax for the treatment of MM, so it cannot be used in clinical practice [ 27 ]. Currently, several clinical trials of venetoclax-based combination chemotherapy for MM with t(11;14) have been completed or are underway, but unanswered questions regarding safety issues such as cytopenia-associated severe infections remains to be resolved [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

IgE Plasma Cell Leukemia Harboring t(11;14) and 1q Amplification

Nakahara

Ogawa

Matsunaga

et al. 2023

Case Reports in Hematology

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IgE plasma cell neoplasm is the rarest subtype of plasma cell neoplasms and is known for its poor prognosis and high incidence of t(11;14). However, t(11;14) has been classified as a standard-risk rather than high-risk cytogenetic abnormality in multiple myeloma. We have been unable to explain the discrepancy that the hallmark of IgE plasma cell neoplasm with a poor prognosis is a standard-risk cytogenetic abnormality. Here, we report a case of IgE primary plasma cell leukemia with extramedullary lesions of the liver, stomach, and lymph nodes. Plasma cell infiltration was pathologically confirmed in each organ. Cytogenetic analysis of plasma cells revealed t(11;14) and amplification of 1q21. Chemotherapy, with immunomodulatory imide drugs, proteasome inhibitors, and CD38 antibodies, was unsuccessful. In IgE plasma cell neoplasm, coexistence of other cytogenetic abnormalities with t(11;14) may be important. Investigating the presence of cytogenetic abnormalities coexisting with t(11;14) is not only useful for evaluating prognosis but also important for understanding the pathogenesis of the disease. Recently, venetoclax, an oral BCL2 inhibitor, has demonstrated promising efficacy in plasma cell neoplasm patients harboring t(11;14). Development of an effective venetoclax-based regimen for treating aggressive IgE plasma cell neoplasm with t(11;14) is expected.

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“…Cast nephropathy is unusual with an involved free light chain of <500 mg/L and renal biopsy should be considered in unexplained renal impairment 31 . Imaging in myeloma is discussed in detail in recent UK and international guidelines 32–35 and cross‐sectional imaging is mandatory.…”

Section: Screeningmentioning

confidence: 99%

“…Bone disease is a common CRAB feature at progression of SMM and may be asymptomatic 99,104 . Diffusion‐weighted MRI is the most sensitive imaging modality for the detection of focal lesions and diffuse infiltration in SMM 35,105,106 and the presence of one focal lesion on MRI may hold prognostic value for progression with bone disease 98 . However, the IMWG serial imaging recommendations are not based on evidence from randomised trials and no assessments of health economic impacts or assessments of capacity have been performed.…”

Section: Monitoring Of Patients With Smouldering Myelomamentioning

confidence: 99%

Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper

Hughes,

Yong,

Ramasamy

et al. 2024

Br J Haematol

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This good practice paper was compiled according to the British Society for Haematology (BSH) process at (https:// b-s-h. org. uk/ media/ 16732/ bsh-guida nce-devel opmen tproce ss-dec-5-18. pdf). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) nomenclature was used to evaluate the levels of evidence and to assess the strength of recommendations. The BSH produces good practice papers to recommend good practice in areas where there is a limited evidence base, but for which a degree of consensus or uniformity is likely to be beneficial to patient care. Literature review detailsA literature search was performed using the EMBASE and MEDLINE databases using the following search terms: monoclonal gammopathy of undetermined significance, multiple myeloma, smouldering (smoldering) multiple myeloma; monoclonal gammopathy, MGUS. Review of the manuscriptReview of the manuscript was performed by the BSH Haemato-Oncology Task Force, the BSH Guidelines Committee and the Haemato-Oncology sounding board of BSH. It has also been reviewed by the UK Myeloma Society and Myeloma UK. I N TRODUC TIONMultiple myeloma (MM) is a clonal bone marrow disorder of plasma cells. MM is preceded by the precursor conditions monoclonal gammopathy of undetermined significance (MGUS) and smouldering myeloma (SMM). SMM sits between MGUS and MM, representing a plasma

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

Cited by 14 publications

References 45 publications

Efficacy and safety of venetoclax-based regimens for the treatment of relapsed/refractory multiple myeloma: a systemic review and meta-analysis

Efficacy and safety of venetoclax-based regimens for the treatment of relapsed/refractory multiple myeloma: a systemic review and meta-analysis

IgE Plasma Cell Leukemia Harboring t(11;14) and 1q Amplification

Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper

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