Daratumumab and dexamethasone is safe and effective for triple refractory myeloma patients: final results of the IFM 2014-04 (Etoile du Nord) trial.

Adult Aged Aged, 80 and over Antibodies, Monoclonal / administration & dosage Antineoplastic Combined Chemotherapy Protocols / administration & dosage Dexamethasone / administration & dosage Disease-Free Survival Female Humans Male Middle Aged Multiple Myeloma / drug therapy Survival Rate

clinical trial daratumumab myeloma therapy

Journal

British journal of haematology

ISSN: 1365-2141

Titre abrégé: Br J Haematol

Pays: England

ID NLM: 0372544

Informations de publication

Date de publication:
11 2019

Historique:

received: 21 03 2019

accepted: 30 04 2019

pubmed: 21 6 2019

medline: 17 6 2020

entrez: 21 6 2019

Statut: ppublish

Résumé

Single agent daratumumab has shown clinical activity in relapsed, refractory multiple myeloma (RRMM). The Intergroupe Francophone du Myélome 2014-04 trial was designed to further investigate daratumumab in combination with dexamethasone in triple RRMM patients. Patients received daratumumab infusions in combination with weekly dexamethasone until disease progression or unacceptable toxicity. Fifty-seven patients were included in the trial and evaluable for response. The overall response rate and the clinical benefit rate were 33% (n = 19) and 48% (n = 27), respectively. Five (8·8%) patients achieved a very good partial response or better. The median time to response was 4 weeks. For responding patients, the median progression-free survival was 6·6 months, compared to 3·7 months (3·0-5·5) for those with a minimal or stable disease. The median overall survival (OS) for all patients was 16·7 months (11·2-24·0). For responding patients, the median OS was 23·23 months, whereas that of patients with progressive disease was 2·97 months. The incidence of infusion-related reactions was 37%; all cases were manageable and did not lead to dose reduction or permanent treatment discontinuation. These data demonstrate that treatment with daratumumab and dexamethasone results in a meaningful long-term benefit with an acceptable safety profile for patients with triple RRMM.

Identifiants

DOI: 10.1111/bjh.16059 PMID: 31218679

pubmed: 31218679

doi: 10.1111/bjh.16059

doi:

Substances chimiques

Antibodies, Monoclonal 0

daratumumab 4Z63YK6E0E

Dexamethasone 7S5I7G3JQL

Types de publication

Clinical Trial Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

Pagination

319-327

Investigateurs

Bertrand Arnulf (B)

Mamoun Dib (M)

Sabine Brechignac-Bureau (S)

Pascal Godmer (P)

Adrian Tempescul (A)

Cecile Fohrer (C)

Lotfi Benboubker (L)

Laurent Voillat (L)

Jean Valère Malfuson (JV)

Clara Mariette (C)

Mourad Tiab (M)

Sophie Rigaudeau (S)

Arnaud Jaccard (A)

Anne-Marie Stoppa (AM)

Jean-Claude Eisenmann (JC)

Philippe Rodon (P)

Brigitte Kolb (B)

Olivier Decaux (O)

Brigitte Onraed (B)

Michel Attal (M)

Cyrille Hulin (C)

Informations de copyright

Références

Aaronson, N.K., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N.J., Filiberti, A., Flechtner, H., Fleishman, S.B. & de Haes, J.C. (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. Journal of the National Cancer Institute, 85, 365-376.

Bladé, J., Samson, D., Reece, D., Apperley, J., Björkstrand, B., Gahrton, G., Gertz, M., Giralt, S., Jagannath, S. & Vesole, D. (1998) Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. British Journal of Haematology, 102, 1115-1123.

Chari, A., Suvannasankha, A., Fay, J.W., Arnulf, B., Kaufman, J.L., Ifthikharuddin, J.J., Weiss, B.M., Krishnan, A., Lentzsch, S., Comenzo, R., Wang, J., Nottage, K., Chiu, C., Khokhar, N.Z., Ahmadi, T. & Lonial, S. (2017) Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood, 130, 974-981.

Chatterjee, S., Daenthanasanmak, A., Chakraborty, P., Wyatt, M.W., Dhar, P., Selvam, S.P., Fu, J., Zhang, J., Nguyen, H., Kang, I., Toth, K., Al-Homrani, M., Husain, M., Beeson, G., Ball, L., Helke, K., Husain, S., Garrett-Mayer, E., Hardiman, G. & Mehrotra, M. (2018) CD38-NAD+Axis regulates immunotherapeutic anti-tumor T cell response. Cell Metabolism, 27, 85-100.e8.

CRAN (2018) The Comprehensive R Archive Network. Available at: https://cran.r-project.org/ [Accessed July 19, 2018].

Dimopoulos, M. (2018) Results from a phase II study of isatuximab as a single agent and in combination with dexamethasone in patients with relapsed/refractory multiple myeloma. Blood, 132, 155.

van de Donk, N.W.C.J., Otten, H.G., El Haddad, O., Axel, A., Sasser, A.K., Croockewit, S. & Jacobs, J.F.M. (2016) Interference of daratumumab in monitoring multiple myeloma patients using serum immunofixation electrophoresis can be abrogated using the daratumumab IFE reflex assay (DIRA). Clinical Chemistry and Laboratory Medicine, 54, 1105-1109.

Durie, B.G.M., Harousseau, J.-L., Miguel, J.S., Bladé, J., Barlogie, B., Anderson, K., Gertz, M., Dimopoulos, M., Westin, J., Sonneveld, P., Ludwig, H., Gahrton, G., Beksac, M., Crowley, J., Belch, A., Boccadaro, M., Cavo, M., Turesson, I., Joshua, D., Vesole, D., Kyle, R., Alexanian, R., Tricot, G., Attal, M., Merlini, G., Powles, R., Richardson, P., Shimizu, K., Tosi, P., Morgan, G. & Rajkumar, S.V.; for the International Myeloma Working Group (2006) International uniform response criteria for multiple myeloma. Leukemia, 20, 1467-1473.

Krejcik, J., Casneuf, T., Nijhof, I.S., Verbist, B., Bald, J., Plesner, T., Syed, K., Liu, K., van de Donk, N.W.C.J., Weiss, B.M., Ahmadi, T., Lokhorst, H.M., Mutis, T. & Sasser, A.K. (2016) Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood, 128, 384-394.

Kumar, S.K., Lee, J.H., Lahuerta, J.J., Morgan, G., Richardson, P.G., Crowley, J., Haessler, J., Feather, J., Hoering, A., Moreau, P., LeLeu, X., Hulin, C., Klein, S.K., Sonneveld, P., Siegel, D., Bladé, J., Goldschmidt, H., Jagannath, S., Miguel, J.S., Orlowski, R., Sutherland, H.J., Bladé, J., Scott, E.C., Oriol, A., Berdeja, J., Gharibo, M., Stevens, D.A., LeBlanc, R., Sebag, M., Callander, N., Jakubowiak, A., White, D., de la Rubia, J., Richardson, P.G., Lisby, S., Feng, H., Uhlar, C.M., Khan, I., Ahmadi, T. & Voorhees, P.M. (2012) Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia, 26, 149-157.

Lokhorst, H.M., Plesner, T., Laubach, J.P., Nahi, H., Gimsing, P., Hansson, M., Minnema, M.C., Lassen, U., Krejcik, J., Palumbo, A., van de Donk, N.W.C.J., Ahmadi, T., Khan, I., Uhlar, C.M., Wang, J., Sasser, A.K., Losic, N., Lisby, S., Basse, L., Brun, N. & Richardson, P.G. (2015) Targeting CD38 with daratumumab monotherapy in multiple myeloma. The New England Journal of Medicine, 373, 1207-1219.

Lonial, S., Weiss, B.M., Usmani, S.Z., Singhal, S., Chari, A., Bahlis, N.J., Belch, A., Krishnan, A., Vescio, R.A., Mateos, M.V., Mazumder, A., Orlowski, R.Z., Sutherland, H.J., Bladé, J., Scott, E.C., Oriol, A., Berdeja, J., Gharibo, M., Stevens, D.A., LeBlanc, R., Sebag, M., Callander, N., Jakubowiak, A., White, D., de la Rubia, J., Richardson, P.G., Lisby, S., Feng, H., Uhlar, C.M., Khan, I., Ahmadi, T. & Voorhees, P.M. (2016) Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. The The Lancet, 387, 1551-1560.

Marlein, C.R., Piddock, R.E., Mistry, J.J., Zaitseva, L., Hellmich, C., Horton, R.H., Zhou, Z., Auger, M.J., Bowles, K.M. & Rushworth, S.A. (2019) CD38-Driven Mitochondrial Trafficking Promotes Bioenergetic Plasticity in Multiple Myeloma. Cancer Research. Available at: http://cancerres.aacrjournals.org/content/early/2019/03/30/0008-5472.CAN-18-0773 [Accessed April 17, 2019].

Nooka, A.K., Kastritis, E., Dimopoulos, M.A. & Lonial, S. (2015) Treatment options for relapsed and refractory multiple myeloma. Blood, 125, 3085-3099.

Phipps, C., Chen, Y., Gopalakrishnan, S. & Tan, D. (2015) Daratumumab and its potential in the treatment of multiple myeloma: overview of the preclinical and clinical development. Therapeutic Advances in Hematology, 6, 120-127.

Rabin, R. & de Charro, F. (2001) EQ-5D: a measure of health status from the EuroQol Group. Annals of Medicine, 33, 337-343.

Röllig, C., Knop, S. & Bornhäuser, M. (2015) Multiple myeloma. The Lancet, 385, 2197-2208.

Stead, M.L., Brown, J.M., Velikova, G., Kaasa, S., Wisløff, F., Child, J.A., Hippe, E., Hjorth, M., Sezer, O. & Selby, P. (1999) Development of an EORTC questionnaire module to be used in health-related quality-of-life assessment for patients with multiple myeloma. European Organization for Research and Treatment of Cancer Study Group on Quality of Life. British Journal of Haematology, 104, 605-611.

Tang, F., Malek, E., Math, S., Schmotzer, C.L. & Beck, R.C. (2018) Interference of therapeutic monoclonal antibodies with routine serum protein electrophoresis and immunofixation in patients with myeloma: frequency and duration of detection of daratumumab and elotuzumab. American Journal of Clinical Pathology, 150, 121-129.

U S Food and Drug Administration Home Page (2015) Available at: https://www.fda.gov/ [Accessed July 19, 2018].

Usmani, S.Z., Weiss, B.M., Plesner, T., Bahlis, N.J., Belch, A., Lonial, S., Lokhorst, H.M., Voorhees, P.M., Richardson, P.G., Chari, A., Sasser, A.K., Axel, A., Feng, H., Uhlar, C.M., Wang, J., Khan, I., Ahmadi, T. & Nahi, H. (2016) Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood, 128, 37-44.

Usmani, S.Z., Diels, J., Ito, T., Mehra, M., Khan, I. & Lam, A. (2017) Daratumumab monotherapy compared with historical control data in heavily pretreated and highly refractory patients with multiple myeloma: An adjusted treatment comparison. American Journal of Hematology, 92, E146-E152.

de Weers, M., Tai, Y.-T., van der Veer, M.S., Bakker, J.M., Vink, T., Jacobs, D.C.H., Oomen, L.A., Peipp, M., Valerius, T., Slootstra, J.W., Mutis, T., Bleeker, W.K., Anderson, K.C., Lokhorst, H.M., van de Winkel, J.G.J. & Parren, P.W.H.I. (2011) Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. Journal of Immunology, 186, 1840-1848.