MOR202 alone and in combination with pomalidomide or lenalidomide in relapsed or refractory multiple myeloma: Data from clinically relevant cohorts from a phase I/IIa study.

Raab, Marc S.; Chatterjee, Manik; Goldschmidt, Hartmut; Agis, Hermine; Blau, Igor W; Einsele, Hermann; Engelhardt, Monika; Ferstl, Barbara; Gramatzki, Martin; Röllig, Christoph; Weisel, Katja; Kloepfer, Pia; Weinelt, Dominika; Endell, Jan; Boxhammer, Rainer; Peschel, Christian

doi:10.1200/jco.2016.34.15_suppl.8012

Cited by 16 publications

(18 citation statements)

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“…All nine patients receiving MOR202 monotherapy derived clinical benefits. In conclusion, MOR202 showed excellent infusion tolerability and overall safety profile [78].…”

Section: Mor202mentioning

confidence: 80%

“…An ongoing phase 1/2a open-label, dose-escalating study in RRMM (ClinicalTrials.gov, NCT01421186) showed that MOR202 was well tolerated with mainly hematological toxicity in doses up to 16 mg/kg [77]. Interim analysis reported that IRs (grade 1) were seen in only one out of 17 patients [78]. Responses were reported in six out of 15 evaluable patients: two very good partial responses and four partial responses, with five out of six still ongoing.…”

Section: Mor202mentioning

confidence: 99%

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Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

Martin

Corzo

Chiron

et al. 2019

Cells

119

151

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CD38 is a transmembrane glycoprotein with ectoenzymatic activity involved in regulation of migration, signal transduction, and receptor-mediated adhesion. CD38 is highly expressed on various malignant cells, including multiple myeloma (MM), and at relatively low levels in other tissues, making it a suitable target for therapeutic antibodies. Several anti-CD38 therapies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab (SAR650984), respectively. Studies have shown that anti-CD38 therapies are effective in the treatment of relapsed/refractory MM and are well tolerated, with infusion reactions being the most common side effects. They can be used as monotherapy or in combination with immunomodulatory agents, such as pomalidomide, or proteasome inhibitors to potentiate their activity. Here we examine isatuximab and several anti-CD38 agents in development that were generated using new antibody engineering techniques and that may lead to more effective CD38 targeting. We also summarize trials assessing these antibodies in MM, other malignancies, and solid organ transplantation. Finally, we propose that further research on the mechanisms of resistance to anti-CD38 therapy and the development of biomarkers and new backbone regimens with CD38 antibodies will be important steps in building more personalized treatment for patients with MM.

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“…All nine patients receiving MOR202 monotherapy derived clinical benefits. In conclusion, MOR202 showed excellent infusion tolerability and overall safety profile [78].…”

Section: Mor202mentioning

confidence: 80%

Section: Mor202mentioning

confidence: 99%

Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

Martin

Corzo

Chiron

et al. 2019

Cells

119

151

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“…Plasma cell surface targets of mAbs that have already demonstrated significant clinical activity either alone or in combination with other approved myeloma drugs include signaling lymphocytic activation molecule F7 (SLAMF7) (elotuzumab [ELO]) and CD38 (daratumumab [DARA], isatuximab [ISA] [SAR659084], and MOR-202). [3][4][5][6][7] Other mAbs directed against MM cellular antigens that have demonstrated at least stable disease include those directed against CD138 (BT062), CD54/ICAM-1 (BI-505), and CD74 (milatuzumab). [8][9][10] The development of therapeutic mAbs for the treatment of MM has also been directed against growth factors and their receptors (eg, interleukin-6, interleukin-6 receptor, insulin-like growth factor-1 or -2, vascular endothelial growth factor, and B-cell activating factor).…”

Section: Targets For Monoclonal Antibody (Mab) Therapymentioning

confidence: 99%

“…6 Unlike DARA and ISA, IRR were rare (14%) when DEX was used as a premedication, which may be due to the absence of CDC with MOR202, which is suspected to be a major contributor of IRR. 37 …”

Section: Mor202mentioning

confidence: 99%

Advances and practical use of monoclonal antibodies in multiple myeloma therapy

Lee

Weber

2016

Hematology

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The use of proteasome inhibitors and immunomodulatory agents in the treatment of myeloma have resulted in significant improvements in patient outcomes over the last decade. Although these agents now form the backbone of current myeloma treatment regimens both in the frontline and in a relapsed setting, drug resistance remains an inevitable challenge that most patients will encounter during their disease course. Hence, new treatment strategies continue to be explored, and the recent regulatory approvals of the monoclonal antibodies (mAbs) daratumumab (DARA) and elotuzumab (ELO), which target the plasma cell surface proteins CD38 and signaling lymphocytic activation molecule F7 (SLAMF7), respectively, have heralded the long-awaited era of antibody-based approaches in the treatment of myeloma. Hoping to build on these advances, a number of other mAbs are in various stages of clinical development, including those targeting myeloma cell surface antigens, the bone marrow microenvironment, and immune effector T cells such as anti-programmed cell death protein 1 antibodies. In this review, the current landscape and practical use of mAb-based therapy in myeloma will be discussed. Learning Objectives• Understand the current landscape of mAb-based therapy in myeloma, with a particular focus on the CD38-targeted therapy with DARA and SLAMF7-targeted therapy with ELO • Become aware of practical issues unique to mAb-based therapy in myeloma including red blood cell compatibility testing with anti-CD38-directed therapy and interference with myeloma laboratory response assessments

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“…However, patients refractory to LEN were excluded from the POLLUX trial, and patients pretreated with POM were excluded from the EQUULEUS trial. Preliminary results from phase I/II trials of other anti‐CD38 antibodies, MOR202, and isatuximab, in combination with IMiDs in relapsed‐refractory MM further emphasize the efficacy of combination treatment with these classes of compounds. The latter trial found an ORR of 54% using isatuximab in combination with lenalidomide even in patients already refractory to lenalidomide.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic monoclonal antibodies in combination with pomalidomide can overcome refractoriness to both agents in multiple myeloma: A case‐based approach

Baertsch

Hundemer

Hillengaß

et al. 2017

Hematological Oncology

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In multiple myeloma (MM), the synergy between immunomodulatory drugs (IMiDs) and monoclonal antibodies (MABs) has been demonstrated in several pivotal trials. However, disease refractory to either class of compounds remains a major therapeutic challenge. We here report on 3 heavily pretreated MM patients who were refractory to pomalidomide as well as to MABs against CD38 (daratumumab) or CD20 (rituximab), respectively, but who responded to retreatment with the same agents in combination. Responses were durable with PFS of 7, 10 (ongoing), and 30 months from initiation of combination treatment. The combination of IMiDs with MABs directed against MM cell surface antigens can overcome refractoriness to both agents.

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MOR202 alone and in combination with pomalidomide or lenalidomide in relapsed or refractory multiple myeloma: Data from clinically relevant cohorts from a phase I/IIa study.

Cited by 16 publications

References 0 publications

Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

Therapeutic Opportunities with Pharmacological Inhibition of CD38 with Isatuximab

Advances and practical use of monoclonal antibodies in multiple myeloma therapy

Therapeutic monoclonal antibodies in combination with pomalidomide can overcome refractoriness to both agents in multiple myeloma: A case‐based approach

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