Development and Validation of Electrochemiluminescence Assays to Measure Free and Total sSLAMF7 in Human Serum in the Absence and Presence of Elotuzumab

Postelnek, Jennifer; Neely, Robert; Robbins, Michael; Gleason, Carol; Peterson, Julie A.; Piccoli, Steven P.

doi:10.1208/s12248-016-9912-3

Cited by 9 publications

(5 citation statements)

References 13 publications

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“…Elotuzumab is a SLAMF7-specific monoclonal antibody recognizing the C2-like domain within the extracellular domain [ 28 ]. In MM patients receiving combination therapy with elotuzumab, bortezomib, and low-dose dexamethasone, free sSLAMF7 levels that were not bound to elotuzumab in serum were significantly decreased when compared with baseline [ 29 ]. On the other hand, serum levels of total sSLAMF7, including those bound and not bound to elotuzumab, were markedly increased after elotuzumab treatment [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…In MM patients receiving combination therapy with elotuzumab, bortezomib, and low-dose dexamethasone, free sSLAMF7 levels that were not bound to elotuzumab in serum were significantly decreased when compared with baseline [ 29 ]. On the other hand, serum levels of total sSLAMF7, including those bound and not bound to elotuzumab, were markedly increased after elotuzumab treatment [ 29 ]. This suggests that serum sSLAMF7 binds to elotuzumab during treatment.…”

Section: Discussionmentioning

confidence: 99%

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Clinical impact of serum soluble SLAMF7 in multiple myeloma

et al. 2018

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The signaling lymphocytic activation molecule family (SLAMF7; also known as CS1 or CD319) is highly expressed on plasma cells from multiple myeloma (MM) as well as natural killer (NK) cells and is a well-known therapeutic target of elotuzumab. The objective of this study was to evaluate the clinical significance of serum soluble SLAMF7 (sSLAMF7) levels in patients with MM (n=103) and furthermore the impact of sSLMF7 on the antitumor activity of anti-SLAMF7 antibody. Thirty-one percent of MM patients, but not patients with monoclonal gammopathy of undetermined significance and healthy controls, had detectable levels of serum sSLAMF7, which were significantly increased in advanced MM patients. Further, MM in sSLAMF7-postive patients exhibited aggressive clinical characteristics with shorter progression-free survival times in comparison with sSLAMF7-negative patients. In responders to MM therapy, the levels of sSLAMF7 were undetectable or decreased compared with those before treatment. In addition, the anti-SLAMF7 antibody-mediated antibody-dependent cellular cytotoxicity of NK cells against MM cell lines was inhibited by recombinant SLAMF7 protein. Thus, our findings suggest that high concentrations of sSLAMF7, which could transiently suppress the therapeutic effects of elotuzumab, may be a useful indicator of disease progression in MM patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinical impact of serum soluble SLAMF7 in multiple myeloma

et al. 2018

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“…This is supported by Olson et al (25) who demonstrated the poor prognostic value of CD229 in MM and Radhakrishnan et al (27) who stated that CD229 is a poor prognostic marker in MM and its target therapy may eradicate terminally differentiated MM cells and clonotypic MMpropagating cells. Radhakrishnan et al (27) also stated that targeting CD229 can treat the MM-resistant cases and potentially providing long-lasting responses and Postelnek et al (28) , who demonstrated the prognostic role of CD319, reported that a high concentration of CD319 in the microenvironment of BM may suppress elotuzumab effects in MM patients. Xie et al (29) supported these results also by reporting that CD319 is included in tumor proliferation in MM inducing tumor cell growth and it is linked to poor prognosis in MM.…”

Section: Discussionmentioning

confidence: 99%

Predictive Value of CD229, CD319 and c-Maf Overexpression for Treatment Response in Multiple Myeloma Patients

Ebian¹,

Wahab²,

Elbasateeny³

et al. 2021

The Egyptian Journal of Hospital Medicine

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Background: Ly-9 (CD229) and SLAMF7 (CD319) are more stable markers that could be used to replace the less stable conventional markers CD138 and CD38 in multiple myeloma (MM) patient follow-up. In those patients, the correlation between these markers and the histopathologic marker c-Maf has not been well investigated. Objective: To assess the predictive value of CD229, CD319, and c-MAF overexpression on outcome of treatment in MM patients. Patients and Methods: 61 newly diagnosed multiple myeloma patients were involved in this prospective study. Flow cytometric analysis of bone marrow (BM) samples for CD229 PE, CD319 PE, CD138 PerCP and CD38FITC as well as BM biopsy immunohistochemically were analyzed for c-Maf expression Results: CD229 and CD319 were highly expressed in (≥93.95%) and (≥95.6%) of MM patients respectively. c-Maf was positive in (29.5%) of patients. In MM patients with high expression of CD229 and CD319 as well as those with c-Maf positivity showed high serum Ca ++ , β2M, CD138 and CD38. CD229 was significantly correlated with CD319, CD38, CD138, β2M and serum Ca (p-values were< 0.001,0.01, 0.01, 0.009, and 0.02 respectively). Patients with overexpression of CD 229, CD319 and c-Maf were more refractory to treatment (p-values were <0.001,<0.001 and <0.001 respectively). Conclusion:We detected that both CD229 and CD319 were significantly overexpressed on MM cells and correlated significantly with CD138 and CD38, suggesting their use as alternative markers for MM diagnosis as well as followup. Patients with CD229,CD319, and c-Maf overexpression were associated with a significant poor response to therapy.

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“…Unlike with dara, gel-shift approaches have not yet been developed to eliminate false positives for elotuzumab. Possible workaround options for the measurement of elotuzumab-induced M-spikes or imunofixation electrophoresis include the SLAMF7 90 or mass spectrometrybased approaches. 62 63 Panel recommendations ► In published trials, infusion-related reactions (IRRs) have been most prevalent with the first infusion.…”

Section: Administration Dosing and Monitoringmentioning

confidence: 99%

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

Shah

Aiello

Avigan

et al. 2020

J Immunother Cancer

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Outcomes in multiple myeloma (MM) have improved dramatically in the last two decades with the advent of novel therapies including immunomodulatory agents (IMiDs), proteasome inhibitors and monoclonal antibodies. In recent years, immunotherapy for the treatment of MM has advanced rapidly, with the approval of new targeted agents and monoclonal antibodies directed against myeloma cell-surface antigens, as well as maturing data from late stage trials of chimeric antigen receptor CAR T cells. Therapies that engage the immune system to treat myeloma offer significant clinical benefits with durable responses and manageable toxicity profiles, however, the appropriate use of these immunotherapy agents can present unique challenges for practicing physicians. Therefore, the Society for Immunotherapy of Cancer convened an expert panel, which met to consider the current role of approved and emerging immunotherapy agents in MM and provide guidance to the oncology community by developing consensus recommendations. As immunotherapy evolves as a therapeutic option for the treatment of MM, these guidelines will be updated.

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Development and Validation of Electrochemiluminescence Assays to Measure Free and Total sSLAMF7 in Human Serum in the Absence and Presence of Elotuzumab

Cited by 9 publications

References 13 publications

Clinical impact of serum soluble SLAMF7 in multiple myeloma

Clinical impact of serum soluble SLAMF7 in multiple myeloma

Predictive Value of CD229, CD319 and c-Maf Overexpression for Treatment Response in Multiple Myeloma Patients

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

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