Baseline and Changes in Serum B-Cell Maturation Antigen Levels Rapidly Indicate Changes in Clinical Status Among Patients with Relapsed/Refractory Multiple Myeloma Starting New Therapy

Bujarski, Sean; Udd, Kyle; Soof, Camilia; Chen, Haiming; Spektor, Tanya M.; Safaie, Tahmineh; Li, Mingjie; Stern, Joshua A.; Wang, Cathy; Xu, Ning; Emamy-Sadr, Marsiye; Swift, Regina A.; Rahbari, Ashkon; Patil, Saurabh; Souther, Eric; Regidor, Bernard; Sutanto, Christine; Berenson, James R.

doi:10.1007/s11523-021-00821-6

Cited by 14 publications

(24 citation statements)

References 28 publications

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“…As more therapies become available, a more reliable and rapid determination of changes in patients' clinical status is critical for treating healthcare professionals to better assess drug efficacy and optimize clinical outcomes. From retrospective studies, we have previously shown that sBCMA is elevated in MM patients and can be used to follow disease status specifically in predicting PFS and OS 2,6,9,10,15 …”

Section: Discussionmentioning

confidence: 99%

“…From retrospective studies, we have previously shown that sBCMA is elevated in MM patients and can be used to follow disease status specifically in predicting PFS and OS. 2,6,9,10,15 In this study, we prospectively determined sBCMA levels for 38 RRMM patients enrolled on a phase 1 clinical trial, evaluating the combination of RUX, LEN and MP; the clinical results from this study have been recently published. 13 sBCMA, serum M-protein and SFLC levels were analyzed weekly during the patients' first 28-day cycle and once monthly thereafter.…”

Section: Discussionmentioning

confidence: 99%

“…19 Although in this prospective study we analyzed a relatively small patient population, the results are promising and consistent with our previous findings showing the value of this new serum biomarker for determining outcomes for MM patients both as a prognostic and monitoring tool. [13][14][15] Additional prospective studies are warranted to further establish the role of sBCMA as a monitoring and prognostic tool for MM patients.…”

Section: F I G U R Ementioning

confidence: 99%

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Use of serum B‐cell maturation antigen levels to predict outcomes for myeloma patients treated with ruxolitinib, lenalidomide and methylprednisolone

Bujarski¹,

Sutanto

Spektor

et al. 2022

Hematological Oncology

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Previous retrospective studies have shown that serum B-cell maturation antigen (sBCMA) levels predict outcomes among patients with multiple myeloma (MM) undergoing new treatments. Specifically, baseline levels and changes during treatment of this protein predict both progression free survival (PFS) and overall survival. However, prospective studies are lacking evaluating sBCMA for determining outcomes among MM patients undergoing new treatments. Thus, we evaluated whether its baseline levels and changes during treatment in the amount of this serum marker predict outcomes among 38 relapsed/refractory MM patients treated with ruxolitinib, lenalidomide and methylprednisolone in a phase 1 trial. Patients with baseline sBCMA levels in the lowest three quartiles had longer PFS (median PFS 136 vs. 28 days; p < 0.0001). This was also shown for patients with baseline levels below the median (median PFS 140 vs. 77 days; p = 0.0225). PFS was shorter for patients whose sBCMA levels increased ≥25% through their first cycle (median PFS: 50 vs. 134 days, p = 0.0022), second cycle (median PFS: 50 vs. 141 days, p = 0.0273), and during the first three cycles of study treatment (median PFS: 50 vs. 220 days, p < 0.0001). No patient whose sBCMA increased ≥25% during cycle 1 responded whereas the majority (58%) of patients whose level increased <25% responded. This is the first prospective study to determine whether sBCMA levels predict outcomes for MM patients undergoing a non-BCMA directed treatment regimen and demonstrates that baseline levels and its changes during treatment predict PFS and the likelihood of responding to their treatment. These results add to the growing literature suggesting that this serum marker will be useful for determining outcomes for patients undergoing treatment for MM.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: F I G U R Ementioning

confidence: 99%

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Use of serum B‐cell maturation antigen levels to predict outcomes for myeloma patients treated with ruxolitinib, lenalidomide and methylprednisolone

Bujarski¹,

Sutanto

Spektor

et al. 2022

Hematological Oncology

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“…Given that γ‐secretase is a ubiquitously expressed membrane protein (Selkoe & Wolfe, 2007), we reason that the constitutive shedding of surface BCMA might make the molecule a weak marker of prognosis. Studies have also suggested the role of soluble BCMA as a prognostic tool in PC neoplasms (Bujarski et al, 2021; Lee et al, 2016; Visram et al, 2021) and highlighted its usefulness in monitoring response to therapy (Ghermezi et al, 2017). In retrospect, we believe that evaluating the expression of surface and soluble BCMA in parallel would have added advantages, although this was beyond the scope of the study.…”

Section: Discussionmentioning

confidence: 99%

Expression levels and patterns of B‐cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent

Sriram

Kunjachan

Khanka

et al. 2022

Cytometry Part B Clinical

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Background Many novel therapies are being evaluated for the treatment of Multiple myeloma (MM). The cell‐surface protein B‐cell maturation antigen (BCMA, CD269) has recently emerged as a promising target for CAR‐T cell and monoclonal‐antibody therapies in MM. However, the knowledge of the BCMA expression‐pattern in myeloma patients from the Indian subcontinent is still not available. We present an in‐depth study of BCMA expression‐pattern on abnormal plasma cells (aPC) in Indian MM patients. Methods We studied BM samples from 217 MM patients (211‐new and 6‐relapsed) with a median age of 56 years (range, 30–78 years & M:F‐2.29) and 20 control samples. Expression levels/patterns of CD269 (clone‐19f2) were evaluated in aPCs from MM patients and in normal PCs (nPC) from uninvolved staging bone marrow samples (controls) using multicolor flow cytometry (MFC). Expression‐level of CD269 was determined as a ratio of mean fluorescent intensity (MFI‐R) of CD269 in PCs to that of non‐B‐lymphocytes and expression‐pattern (homogenous/heterogeneous) as coefficient‐of‐variation of immunofluorescence (CVIF). Results Median (range) percentage of CD269‐positive abnormal‐PCs in total PCs was 71.6% (0.49–99.29%). The MFI‐R (median, range) of CD269 was significantly higher in aPCs (4.13, 1.12–26.88) than nPCs (3.33, 1.23–12.87), p < .0001. Median (range) MFI of CD269 at diagnosis and relapse were 2.39 (0.77–9.57) and 2.66 (2.15–3.23) respectively. CD269 levels were similar at diagnosis and relapse, p = .5529. Conclusions We demonstrated that BCMA/CD269 is highly expressed in aPCs from a majority of MM patients, both at diagnosis and relapse. Thus, BCMA is a valuable target for therapy for Indian MM patients.

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“…Studies of sBCMA levels were emerging in the field of multiple myeloma (MM), in which sBCMA levels were correlated with diagnosis, transformation, treatment response, progression free survival, overall survival, etc. [11][12][13] sBCMA also affects the effectiveness of chimeric antigen receptor T cell therapy and anti-BCMA therapy in MM. 14,15 Although how sBCMA is secreted has not been fully elucidated, its proteolytic shedding from cell-surface by γ-secretase is a widely accepted way currently.…”

Section: Introductionmentioning

confidence: 99%

Serum levels and significance of soluble B-cell maturation antigen in childhood-onset systemic lupus erythematosus with renal involvement

Lin

Cheng

et al. 2023

Lupus

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Objective The aim of this study was to investigate serum levels of soluble B-cell maturation antigen (sBCMA) in childhood-onset systemic lupus erythematous (cSLE) patients with renal involvement, and to elucidate their association with clinical characteristics. Methods 116 cases of cSLE patients with renal involvement (84 females and 32 males; median age 11.6 (10.1, 12.9) years) hospitalized in Department of Pediatric Nephrology and Rheumatology, the First Affiliated Hospital, Sun Yat-sen University and 31 healthy controls (HCs) were enrolled. Serum concentrations of sBCMA were determined using enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory information of cSLE patients were retrospectively analyzed. Results Serum sBCMA levels were significantly increased in primary cSLE when compared with treated cSLE patients and HCs, whereas there was no significant difference between treated cSLE patients and HCs. Patients with high disease activity displayed higher serum sBCMA levels compared with those with no or mild to moderate disease activity. Positive correlation was observed between serum sBCMA levels and systemic lupus erythematosus disease activity index-2K (SLEDAI-2K), antinuclear antibody titers, anti-double-stranded DNA titers, erythrocyte sedimentation rate, and immunoglobulin G levels, while sBCMA levels were negatively correlated with blood white blood cell count, hemoglobin, platelet count, complement C3 and C4 levels. Serum sBCMA levels decreased as disease ameliorated after treatments among 11 cases with follow-up examinations. Conclusions In cSLE patients with renal involvement, serum sBCMA levels correlated significantly with disease activity, immunological, and hematological parameters, but not with renal parameters. Our results suggest the potential and significance of serum sBCMA as a biomarker in cSLE patients.

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Baseline and Changes in Serum B-Cell Maturation Antigen Levels Rapidly Indicate Changes in Clinical Status Among Patients with Relapsed/Refractory Multiple Myeloma Starting New Therapy

Cited by 14 publications

References 28 publications

Use of serum B‐cell maturation antigen levels to predict outcomes for myeloma patients treated with ruxolitinib, lenalidomide and methylprednisolone

Use of serum B‐cell maturation antigen levels to predict outcomes for myeloma patients treated with ruxolitinib, lenalidomide and methylprednisolone

Expression levels and patterns of B‐cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent

Serum levels and significance of soluble B-cell maturation antigen in childhood-onset systemic lupus erythematosus with renal involvement

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