Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL

Suzuki, Yuhko; Yoshida, Tsutomu; Wang, Guoqin; Togano, Tomiteru; Miyamoto, Shunsuke; Miyazaki, Kôji; Iwabuchi, Kazuya; Nakayama, Meijin; Horie, Ryouichi; Niitsu, Nozomi; Sato, Yuichi; Nakamura, Naoya

doi:10.1007/s00277-012-1407-4

Cited by 23 publications

(21 citation statements)

References 31 publications

(38 reference statements)

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“…Several other clinical studies have also shown that efficacy of monoclonal antibodies including rituximab, 37,38 alemtuzumab, 39 and trastuzumab 40,41 is partly dependent on target antigen expression. Importantly, it is unlikely that CD38 is a general prognostic factor in MM.…”

Section: Discussionmentioning

confidence: 95%

CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma

Nijhof

Casneuf

Velzen

et al. 2016

Blood

311

376

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Key Points• Response to the CD38-targeting antibody daratumumab is significantly associated with CD38 expression levels on the tumor cells.• Resistance to daratumumab is accompanied by increased expression of complementinhibitory proteins.The anti-CD38 monoclonal antibody daratumumab is well tolerated and has high single agent activity in heavily pretreated relapsed and refractory multiple myeloma (MM). However, not all patients respond, and many patients eventually develop progressive disease to daratumumab monotherapy. We therefore examined whether pretreatment expression levels of CD38 and complement-inhibitory proteins (CIPs) are associated with response and whether changes in expression of these proteins contribute to development of resistance. In a cohort of 102 patients treated with daratumumab monotherapy (16 mg/kg), we found that pretreatment levels of CD38 expression on MM cells were significantly higher in patients who achieved at least partial response (PR) compared with patients who achieved less than PR. However, cell surface expression of the CIPs, CD46, CD55, and CD59, was not associated with clinical response. In addition, CD38 expression was reduced in both bone marrow-localized and circulating MM cells, following the first daratumumab infusion. CD38 expression levels on MM cells increased again following daratumumab discontinuation. In contrast, CD55 and CD59 levels were significantly increased on MM cells only at the time of progression. All-trans retinoic acid increased CD38 levels and decreased CD55 and CD59 expression on MM cells from patients who developed daratumumab resistance, to approximately pretreatment values. This resulted in significant enhancement of daratumumab-mediated complement-dependent cytotoxicity. Together, these data demonstrate an important role for CD38 and CIP expression levels in daratumumab sensitivity and suggest that therapeutic combinations that alter CD38 and CIP expression levels should be investigated in the treatment of MM. These trials were registered at www.clinicaltrials.gov as #NCT00574288 (GEN501) and #NCT01985126 (SIRIUS). (Blood. 2016;128(7):959-970)

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Section: Discussionmentioning

confidence: 95%

CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma

Nijhof

Casneuf

Velzen

et al. 2016

Blood

311

376

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“…CD30 expression correlates with a unique gene expression signature suggesting a distinct molecular basis for its favorable outcome. However, the combination of CD30 and EBV expression in immunocompetent patients was correlated with an extremely aggressive clinical course [8]. The current case is a refractory PTLD, which usually has poor prognosis [9].…”

Section: Discussionmentioning

confidence: 74%

“…CD30 was found to be variably positive in 81% of PTLD/DLBCL [7] and in about 14% of immunocompetent patients with DLBCL [8]. CD30 expression is reported to be associated with a favorable outcome in PTLD/DLBCL, regardless of EBV status [7].…”

Section: Discussionmentioning

confidence: 98%

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Diffuse Large B-Cell Lymphoma Trans-differentiating into CD30 Positive Anaplastic Large Cell-like Lymphoma

Bains¹

2017

Ann Hematol Oncol

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Post-Transplant Lymphoproliferative Disorders (PTLD) is mostly of B-cell origin. "Composite" PTLD with diffuse large B-cell lymphoma (DLBCL) and T/ anaplastic large cell lymphoma component are extremely rare. We report a case of PTLD after heart transplant with two distinct components. The patient was initially diagnosed with monomorphic PTLD/DLBCL, EBV negative involving the intestinal wall, occurring nine years after heart transplantation. Sixteen years post-transplant, the lymphoma recurred involving the intestine and showed two distinct components: DLBCL and anaplastic large cell lymphoma with strong homogeneous expression of CD45 and CD30 while lacking B-and T-cell lineage markers mimicking Anaplastic Large Cell Lymphoma (ALCL), ALK negative with a null-cell phenotype and TIA-1 expression. At this time, diffuse lymphadenopathy was also present and a jugular lymph node biopsy prior to the intestinal resection, purely demonstrated only the anaplastic large lymphoma cells with a null-cell phenotype leading to the diagnosis of ALCL, ALK negative. However, molecular studies performed on the anaplastic large cell component identified strongly positive clonal IgH gene rearrangement, identical to the prior lymphoma. Extensive sampling from the intestinal resection specimen identified a transitioning phase between two morphologically and immunohistochemically separate components. This is a unique case of PTLD which demonstrates an immunophenotypic lineage plasticity of the neoplastic cells over an extended post-transplant period.

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“…Diffuse large B-cell lymphoma (DLBCL) cells generally express the pan B-cell marker CD20, which is an important target for treatment. In their study of CD20 levels at onset of disease in patients with DLBCL, Suzuki et al (12) found that CD20 negative status showed significantly inferior OS and progression-free survival compared to patients who were CD20 normal.To date, there is limited information on the prognostic value of CD20 in CLL; it is important to shed light on the real function of this B-lineage differentiation molecule. The aim of our study was to study the correlation between CD20 expression and the clinical-biological characteristics of CLL patients.…”

mentioning

confidence: 99%

High levels of CD20 expression predict good prognosis in chronic lymphocytic leukemia

et al. 2013

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Heterogeneity of CD20 expression exists in chronic lymphocytic leukemia (CLL), therefore, we explored the prognostic significance of CD20 expression in Chinese patients with CLL. Multiparameter flow cytometry was used to detect the expression of CD20 in CD5 + CD19 + cells. In 172 CLL patients, the median expression percent of CD20 was 97.82% (range, 0-100), and the median mean fluorescence intensity (MFI) of CD20 in CLL cells was 731.45 (range, 0.00-9071.90). The percentage of CD20 + cells in the patient group with mutated variable region of immunoglobulin genes (IGHV) was higher than in the non-mutant IGHV group (mean, 92.1% vs 80.4%, P < 0.001). There were no differences in the MFI of CD20 + cells in all prognostic factor groups. Representation of the data using a receiver operating characteristic plot reflected separation between the two IGHV groups, with an area under the curve of 0.661 (95% confidence interval, 0.569-0.753). At the cut-off value of 60.3% for percentage of CD20, the sensitivity and specificity were 90.00% and 38.46%, respectively. Patients whose percentage of CD20 antigen was above 60.3% had longer treatment-free survival (hazard ratio, 0.452; 95% confidence interval, 0.232-0.884, P = 0.020). Percentage and MFI of CD20 were the variables not associated with treatment-free survival by multivariate Cox regression analysis (P < 0.05). High level of CD20 expression in de novo CLL appears to be associated with a good prognosis. (Cancer Sci 2013; 104: 996-1001) C hronic lymphocytic leukemia (CLL), the most frequently occurring leukemia in adults in North America and Europe, is a heterogeneous disease with variable clinical presentation and evolution.(1) In recent years, the significant increase in understanding the pathogenesis of CLL has been translated into a biologically oriented assessment of prognosis. In particular, there has been major progress in the identification of both molecular and cellular markers that may predict disease progression.(2,3) Two major molecular subtypes can be distinguished, characterized by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes (IGHV) that features in CLL. However, IGHV gene sequencing remains a demanding technique, so many studies have focused on the identification of alternative markers with similar prognostic significance, and whose expression is easier to investigate, such as CD38 and zeta-associated protein-70 (ZAP-70). (4,5) A great deal of renewed interest in CD20 membrane protein has emerged since 1997, when the chimeric anti-CD20 mAb rituximab was approved for use in relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma. Rituximab is commonly incorporated into CD20-positive B-cell lymphoma therapy, including CLL, to improve response and prognosis. The CD20 expression level might correlate with treatment outcome in CLL patients. Tam et al. (6) showed that CLL patients with trisomy 12 showed strong expression of CD20 and had a high rate of response to rituximab-based therapy. H...

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Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL

Cited by 23 publications

References 31 publications

CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma

CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma

Diffuse Large B-Cell Lymphoma Trans-differentiating into CD30 Positive Anaplastic Large Cell-like Lymphoma

High levels of CD20 expression predict good prognosis in chronic lymphocytic leukemia

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