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Daratumumab is a new treatment for patients with myeloma. While many patients benefit from this treatment some do not and the mechanism(s) of failure are poorly understood. This study aims to clarify aspects of resistance to treatment with daratumumab in order to improve patient outcomes in the future.
The effector mechanisms of daratumumab have been extensively studied in vitro, but the in vivo correlates and key determinants of success or failure when daratumumab is used alone or in combination with lenalidomide for treatment of patients with myeloma have not been clarified.
There is potentially a wide spectrum of factors that may influence the quality and duration of response following treatment with daratumumab. The integrity of the patient's immune system may be important. Prior lines of chemotherapy or the myeloma disease itself may impair humural (i.e. complement) or cellular (i.e. ADCC) effector mechanisms that are of importance for the response to daratumumab. Also intrinsic properties of the tumor cells or interactions between myeloma cells and the bone marrow microenvironment could make the myeloma cells refractory to daratumumab.
A better understanding of these variables may enable us to improve the quality and duration of daratumumab-induced responses and make daratumumab-based therapies more effective in the near future.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dara len dex | Experimental | Daratumumab in combination with lenalidomide and dexamethasone |
|
| Len dex | Active Comparator | Lenalidomide in combination with dexamethasone |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Daratumumab | Drug | Treatment of myeloma patients with Daratumumab |
|
| Measure | Description | Time Frame |
|---|---|---|
| Response by IMWG criteria | Assessed by M-component in blood and urine samples | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| T cell subset numbers | Measured in bood and bone marrow aspirates | 4 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Torben Plesner, MD | Vejle Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Hematology Vejle Hospital | Vejle | 7100 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25798669 | Result | Franssen LE, van de Donk NW, Emmelot ME, Roeven MW, Schaap N, Dolstra H, Hobo W, Lokhorst HM, Mutis T. The impact of circulating suppressor cells in multiple myeloma patients on clinical outcome of DLIs. Bone Marrow Transplant. 2015 Jun;50(6):822-8. doi: 10.1038/bmt.2015.48. Epub 2015 Mar 23. | |
| 25760767 | Result |
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| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D054219 | Neoplasms, Plasma Cell |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C556306 | daratumumab |
| D000077269 | Lenalidomide |
| D003907 | Dexamethasone |
| ID | Term |
|---|---|
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
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| Lenalidomide | Drug | Treatment of myeloma patients |
|
| Dexamethasone | Drug | Treatment of myeloma patients |
|
| Overdijk MB, Verploegen S, Bogels M, van Egmond M, Lammerts van Bueren JJ, Mutis T, Groen RW, Breij E, Martens AC, Bleeker WK, Parren PW. Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma. MAbs. 2015;7(2):311-21. doi: 10.1080/19420862.2015.1007813. |
| D002318 |
| Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D009930 |
| Organic Chemicals |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |