Accelerated progression of multiple myeloma during anti-CD20 (Rituximab) therapy

Korte, Wolfgang; Jost, C.; Cogliatti, Sergio; Hess, U.; Cerny, Thomas

doi:10.1023/a:1008310819049

Cited by 16 publications

(9 citation statements)

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“…Of note, we have observed that the initial response to MM treatment was associated with higher baseline CD3 + CD20 dim cells, while the two MM patients and the MGUS patient who died had the lowest recorded levels, suggesting that such expansions may be associated with an antitumour response. Consequently, because the CD20 molecule expressed on T cells retains antibody binding capacity, accelerated progression of MM during anti‐CD20 therapy (Korte et al , 1999) may be related to the deletion of CD20‐expressing cytotoxic T cells. As these T cells may contribute to the control and/or modulation of the malignant B‐cell clone, further studies should investigate their possibly unique function in plasma cell dyscrasias.…”

Section: Discussionmentioning

confidence: 99%

Expansion of CD8⁺ T cells that express low levels of the B cell‐specific molecule CD20 in patients with multiple myeloma

Katopodis

Liossis

Viglis³

et al. 2003

Br J Haematol

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Summary. An expanded cytotoxic/memory T‐cell subpopulation expressing low levels of the B‐cell‐specific CD20 molecule was found in peripheral blood and bone marrow of patients with multiple myeloma at the time of diagnosis, but returned to normal levels following treatment. CD3+CD20dim cells were also increased in monoclonal gammopathy of unknown significance albeit at lower levels. Lower CD3+CD20dim cell numbers at baseline may be associated with lack of response to treatment and a poor outcome. Because expansion of these T cells may be related to disease status, further studies should investigate their potentially unique function in plasma cell dyscrasias.

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Section: Discussionmentioning

confidence: 99%

Expansion of CD8⁺ T cells that express low levels of the B cell‐specific molecule CD20 in patients with multiple myeloma

Katopodis

Liossis

Viglis³

et al. 2003

Br J Haematol

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“…In general, myeloma patients (Table I; Korte et al, 1999;Lim et al, 2004). Cytopenias, primarily lymphopenia, which can be grade 3 or 4 in approximately 40% of patients, are common with rituximab.…”

Section: Adverse Effects Of Anti-cd20 Therapymentioning

confidence: 99%

Anti‐CD20 monoclonal antibody therapy in multiple myeloma

et al. 2008

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SummaryCD20 is a particularly appealing target that is expressed on the surface of almost all B cells, with no significant shedding, secretion or internalization. In contrast to the demonstrated efficacy of anti-CD20 strategies in various B-cell lymphoproliferative disorders, the role of such therapy in multiple myeloma is undetermined and controversial. The expression of CD20 by myeloma cells is heterogeneous, and can be detected only in 13-22% of patients. However, there is increasing interest in testing anti-CD20 therapy in myeloma because of recent studies suggesting the existence of clonogenic CD20-positive precursor B cells in the disease. This article reviews the rationale, preclinical and clinical activity of anti-CD20 therapy in myeloma. Clinical trials show that anti-CD20 therapy with rituximab elicits a partial response in approximately 10% of CD20 + patients with multiple myeloma. In addition, there is preliminary evidence of disease stabilization in 50-57% of CD20 + patients for a period of 10-27 months. Further largescale clinical trials are therefore needed to establish the role of this promising strategy in the treatment of myeloma.

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“…Early clinical trials of mAbs targeting CD20 and CD38 have conveyed only very limited benefit, if any, to the treatment of MM. [1][2][3] In recent years, efforts have been made to identify potential therapeutic mAbs by defining alternative or novel MM target antigens, ie, CD40, 4,5 IL6R, 6 HM1.24, 7 CD74, 8 TRAIL-R1, 9 CS1, 10 as well as to conjugate mAbs with classic or novel drugs to specifically kill MM cells, ie, CD56-maytansinoid (DM1), 11 CD138-DM1/DM4. 12 Development of mAbs with improved cytotoxicity, targeting new and known myeloma specific antigens, continues to be an active research area in novel immunotherapeutics for MM.…”

mentioning

confidence: 99%

“…XmAb5592 was formulated in 10mM sodium phosphate, 150mM sodium chloride, and 0.01% polysorbate 20 (pH 7.0), and administered at 20 mg/kg as a single 1-hour intravenous infusion to the left saphenous vein. Blood samples drawn from the cephalic or femoral veins were collected predose and throughout the duration of the study (1,2,3,4,7,14,21, and 28 days after XmAb5592 injection). Bone marrow aspirates were collected from the humerus predose, and at day 7, 14, and before necropsy at day 28.…”

mentioning

confidence: 99%

Potent in vitro and in vivo activity of an Fc-engineered humanized anti-HM1.24 antibody against multiple myeloma via augmented effector function

Tai

Horton

Kong

et al. 2012

Blood

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HM1.24, an immunologic target for multiple myeloma (MM) cells, has not been effectively targeted with therapeutic monoclonal antibodies (mAbs). In this study, we investigated in vitro and in vivo anti-MM activities of XmAb5592, a humanized anti-HM1.24 mAb with Fc-domain engineered to significantly enhance FcγR binding and associated immune effector functions. XmAb5592 increased antibody-dependent cellular cytotoxicity (ADCC) several fold relative to the anti-HM1.24 IgG1 analog against both MM cell lines and primary patient myeloma cells. XmAb5592 also augmented antibody dependent cellular phagocytosis (ADCP) by macrophages. Natural killer (NK) cells became more activated by XmAb5592 than the IgG1 analog, evidenced by increased cell surface expression of granzyme B-dependent CD107a and MM cell lysis, even in the presence of bone marrow stromal cells. XmAb5592 potently inhibited tumor growth in mice bearing human MM xenografts via FcγR-dependent mechanisms, and was significantly more effective than the IgG1 analog. Lenalidomide synergistically enhanced in vitro ADCC against MM cells and in vivo tumor inhibition induced by XmAb5592. A single dose of 20 mg/kg XmAb5592 effectively depleted both blood and bone marrow plasma cells in cynomolgus monkeys. These results support clinical development of XmAb5592, both as a monotherapy and in combination with lenalidomide, to improve patient outcome of MM.

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Accelerated progression of multiple myeloma during anti-CD20 (Rituximab) therapy

Cited by 16 publications

References 10 publications

Expansion of CD8⁺ T cells that express low levels of the B cell‐specific molecule CD20 in patients with multiple myeloma

Expansion of CD8⁺ T cells that express low levels of the B cell‐specific molecule CD20 in patients with multiple myeloma

Anti‐CD20 monoclonal antibody therapy in multiple myeloma

Potent in vitro and in vivo activity of an Fc-engineered humanized anti-HM1.24 antibody against multiple myeloma via augmented effector function

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Accelerated progression of multiple myeloma during anti-CD20 (Rituximab) therapy

Cited by 16 publications

References 10 publications

Expansion of CD8+ T cells that express low levels of the B cell‐specific molecule CD20 in patients with multiple myeloma

Expansion of CD8+ T cells that express low levels of the B cell‐specific molecule CD20 in patients with multiple myeloma

Anti‐CD20 monoclonal antibody therapy in multiple myeloma

Potent in vitro and in vivo activity of an Fc-engineered humanized anti-HM1.24 antibody against multiple myeloma via augmented effector function

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Product

Resources

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Expansion of CD8⁺ T cells that express low levels of the B cell‐specific molecule CD20 in patients with multiple myeloma

Expansion of CD8⁺ T cells that express low levels of the B cell‐specific molecule CD20 in patients with multiple myeloma