Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b–2 dose-escalation study

The Lancet Haematology

Volumn 2, Issue 12, 2015, Pages e516-e527

  Richardson, Paul G ^a,b   Jagannath, Sundar ^b,c   Moreau, Philippe ^d   Jakubowiak, Andrzej J ^b,e   Raab, Marc S ^f   Facon, Thierry ^g   Vij, Ravi ^b,h   White, Darrell ⁱ   Reece, Donna E ^j   Benboubker, Lotfi ^k   Zonder, Jeffrey ^b,l   Tsao, L Claire ^m   Anderson, Kenneth C ^a,b   Bleickardt, Eric ⁿ   Singhal, Anil K ^m   Lonial, Sagar ^b,o  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b Multiple Myeloma Research Consortium   (United States)

^c MOUNT SINAI MEDICAL CENTER   (United States)

^d NANTES UNIVERSITY HOSPITAL   (France)

^e UNIVERSITY OF CHICAGO   (United States)

^f UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^g LILLE UNIVERSITY HOSPITAL   (France)

^h WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

ⁱ DALHOUSIE UNIVERSITY   (Canada)

^j PRINCESS MARGARET HOSPITAL   (Canada)

^k CHU BRETONNEAU   (France)

^l KARMANOS CANCER INSTITUTE   (United States)

^m ABBVIE INC   (United States)

ⁿ BRISTOL MYERS SQUIBB   (United States)

^o EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

DEXAMETHASONE; ELOTUZUMAB; LENALIDOMIDE; M PROTEIN; NEUTRALIZING ANTIBODY; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; THALIDOMIDE;

ADULT; AGED; ANEMIA; APPETITE DISORDER; ARTHRALGIA; ARTICLE; ASTHENIA; BACKACHE; BLURRED VISION; BONE PAIN; BRONCHITIS; CANCER GROWTH; CANCER RECURRENCE; CONSTIPATION; CONTROLLED STUDY; COUGHING; DIARRHEA; DIZZINESS; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DYSGEUSIA; DYSPEPSIA; DYSPNEA; FAINTNESS; FATIGUE; FEMALE; FEVER; HEADACHE; HUMAN; HYPERGLYCEMIA; IMMUNOASSAY; INFLUENZA; INSOMNIA; LEUKOPENIA; LYMPHOCYTOPENIA; MALE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MUSCLE SPASM; NAUSEA; NEUTROPENIA; NIGHT SWEAT; OPEN STUDY; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; RANDOMIZED CONTROLLED TRIAL; RASH; RHINITIS; RHINOPHARYNGITIS; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; UPPER RESPIRATORY TRACT INFECTION; VOMITING; CANADA; CLINICAL TRIAL; FRANCE; GERMANY; MIDDLE AGED; PHASE 1 CLINICAL TRIAL; UNITED STATES; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CANADA; DEXAMETHASONE; FEMALE; FRANCE; GERMANY; HUMANS; MALE; MIDDLE AGED; MULTIPLE MYELOMA; THALIDOMIDE; TREATMENT OUTCOME; UNITED STATES;

EID: 84964968270     PISSN: None     EISSN: 23523026     Source Type: Journal    
DOI: 10.1016/S2352-3026(15)00197-0     Document Type: Article

References (40)

1. 1 Tai, YT, Dillon, M, Song, W, et al. Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu. Blood 112 (2008), 1329–1337.
2. 2 Hsi, ED, Steinle, R, Balasa, B, et al. CS1, a potential new therapeutic antibody target for the treatment of multiple myeloma. Clin Cancer Res 14 (2008), 2775–2784.
3. 3 Harousseau, JL, Dreyling, M, Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 21:suppl 5 (2010), v155–v157.
4. 4 Romano, A, Conticello, C, Cavalli, M, et al. Salvage therapy of multiple myeloma: the new generation drugs. Biomed Res Int, 2014, 2014, 456037.
5. 5 Pozzi, S, Marcheselli, L, Bari, A, et al. Survival of multiple myeloma patients in the era of novel therapies confirms the improvement in patients younger than 75 years: a population-based analysis. Br J Haematol 163 (2013), 40–46.
6. 6 Mitsiades, CS, Hideshima, T, Chauhan, D, et al. Emerging treatments for multiple myeloma: beyond immunomodulatory drugs and bortezomib. Semin Hematol 46 (2009), 166–175.
7. 7 Dimopoulos, M, Spencer, A, Attal, M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357 (2007), 2123–2132.
8. 8 Weber, DM, Chen, C, Niesvizky, R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 357 (2007), 2133–2142.
9. 9 Hou, J, Du, X, Jin, J, et al. A multicenter, open-label, phase 2 study of lenalidomide plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma: the MM-021 trial. J Hematol Oncol, 6, 2013, 41.
10. 10 Richardson, PG, Weller, E, Jagannath, S, et al. Multicenter, phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed and relapsed/refractory multiple myeloma. J Clin Oncol 27 (2009), 5713–5719.
11. 11 Blade, J, de Larrea, CF, Rosinol, L, Incorporating monoclonal antibodies into the therapy of multiple myeloma. J Clin Oncol 30 (2012), 1904–1906.
12. 12 Lonial, S, Mitsiades, CS, Richardson, PG, Treatment options for relapsed and refractory multiple myeloma. Clin Cancer Res 17 (2011), 1264–1277.
13. 13 Maio, M, Grob, JJ, Aamdal, S, et al. Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial. J Clin Oncol 33 (2015), 1191–1196.
14. 14 Robert, C, Long, GV, Brady, B, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372 (2015), 320–330.
15. 15 Hainsworth, JD, Litchy, S, Burris, HA III, et al. Rituximab as first-line and maintenance therapy for patients with indolent non-Hodgkin's lymphoma. J Clin Oncol 20 (2002), 4261–4267.
16. 16 Cannons, JL, Tangye, SG, Schwartzberg, PL, SLAM family receptors and SAP adaptors in immunity. Annu Rev Immunol 29 (2011), 665–705.
17. 17 Collins, SM, Bakan, CE, Swartzel, GD, et al. Elotuzumab directly enhances NK cell cytotoxicity against myeloma via CS1 ligation: evidence for augmented NK cell function complementing ADCC. Cancer Immunol Immunother 62 (2013), 1841–1849.
18. 18 Guo, H, Cruz-Munoz, ME, Wu, N, Robbins, M, Veillette, A, Immune cell inhibition by SLAMF7 is mediated by a mechanism requiring Src kinases, CD45, and SHIP-1 that is defective in multiple myeloma cells. Mol Cell Biol 35 (2015), 41–51.
19. 19 van Rhee, F, Szmania, SM, Dillon, M, et al. Combinatorial efficacy of anti-CS1 monoclonal antibody elotuzumab (HuLuc63) and bortezomib against multiple myeloma. Mol Cancer Ther 8 (2009), 2616–2624.
20. 20 Rice, AG, Balasa, B, Yun, R, Belmar, N, Starling, G, Natural killer cell activation, cytokine production, and cytotoxicity in human PBMC/myeloma cell co-cultures exposed to elotuzumab alone or in combination with lenalidomide (abst 0813). Haematologica, 97(suppl 1), 2012, 333.
21. 21 Godfrey, J, Benson, DM Jr, The role of natural killer cells in immunity against multiple myeloma. Leuk Lymphoma 53 (2012), 1666–1676.
22. 22 Balasa, B, Yun, R, Belmar, NA, et al. Elotuzumab enhances natural killer cell activation and myeloma cell killing through interleukin-2 and TNF-alpha pathways. Cancer Immunol Immunother 64 (2015), 61–73.
23. 23 Zonder, JA, Mohrbacher, AF, Singhal, S, et al. A phase 1, multicenter, open-label, dose escalation study of elotuzumab in patients with advanced multiple myeloma. Blood 120 (2012), 552–559.
24. 24 Van Schie, KA, Wolbink, GJ, Rispens, T, Cross-reactive and pre-existing antibodies to therapeutic antibodies—effects on treatment and immunogenicity. MAbs 7 (2015), 662–671.
25. 25 Lonial, S, Vij, R, Harousseau, JL, et al. Elotuzumab in combination with lenalidomide and low-dose dexamethasone in relapsed or refractory multiple myeloma. J Clin Oncol 30 (2012), 1953–1959.
26. 26 Palumbo, A, Rajkumar, SV, San Miguel, JF, et al. International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol 32 (2014), 587–600.
27. 27 Chng, WJ, Dispenzieri, A, Chim, CS, et al. IMWG consensus on risk stratification in multiple myeloma. Leukemia 28 (2014), 269–277.
28. 28 Harousseau, JL, Dimopoulos, MA, Wang, M, et al. Better quality of response to lenalidomide plus dexamethasone is associated with improved clinical outcomes in patients with relapsed or refractory multiple myeloma. Haematologica 95 (2010), 1738–1744.
29. 29 Axel, AE, McCudden, CR, Xie, H, Hall, BM, Sasser, AK, Development of clinical assay to mitigate daratumumab, an IgG1K monoclonal antibody, interference with serum immunofixation (IFE) and clinical assessment of M-protein response in multiple myeloma. Cancer Res, 74, 2014, 2563 (abstr).
30. 30 Genzen, JR, Kawaguchi, KR, Furman, RR, Detection of a monoclonal antibody therapy (ofatumumab) by serum protein and immunofixation electrophoresis. Br J Haematol 155 (2011), 123–125.
31. 31 McCudden, CR, Voorhees, PM, Hainsworth, SA, et al. Interference of monoclonal antibody therapies with serum protein electrophoresis tests. Clin Chem 56 (2010), 1897–1899.
32. 32 Stewart, AK, Rajkumar, SV, Dimopoulos, MA, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 372 (2015), 142–152.
33. 33 Ascierto, PA, Marincola, FM, What have we learned from cancer immunotherapy in the last 3 years?. J Transl Med, 12, 2014, 141.
34. 34 Plesner, T, Arkenau, H-T, Lokhorst, HM, et al. Safety and efficacy of daratumumab with lenalidomide and dexamethasone in relapsed or relapsed, refractory multiple myeloma. Proc Am Soc Clin Oncol, 32(suppl), 2014 abstr 8533.
35. 35 Dimopoulos, MA, Richardson, PG, Brandenburg, N, et al. A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide. Blood 119 (2012), 2764–2767.
36. 36 McCarthy, PL, Owzar, K, Hofmeister, CC, et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 366 (2012), 1770–1781.
37. 37 Attal, M, Lauwers-Cances, V, Marit, G, et al. Lenalidomide maintenance after stem-cell transplantation for multiple myeloma. N Engl J Med 366 (2012), 1782–1791.
38. 38 Benboubker, L, Dimopoulos, MA, Dispenzieri, A, et al., for the FIRST Trial Team. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med 371 (2014), 906–917.
39. 39 McCarthy, PL, Einsele, H, Attal, M, Giralt, S, The emerging role of consolidation and maintenance therapy for transplant-eligible multiple myeloma patients. Expert Rev Hematol 7 (2014), 55–66.
40. 40 Lonial, S, Dimopoulos, M, Palumbo, A, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med 373 (2015), 621–631.