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Review
. 2021 Feb 17:10:624661.
doi: 10.3389/fonc.2020.624661. eCollection 2020.

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments

Massimo Offidani  1 , Laura Corvatta  1 , Sonia Morè  1 , Davide Nappi  2 , Giovanni Martinelli  3 , Attilio Olivieri  1 , Claudio Cerchione  3
Affiliations
Review

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments

Massimo Offidani et al. Front Oncol. .

Abstract

Immunotherapy is changing the paradigm of multiple myeloma (MM) management and daratumumab is the first-in-class human monoclonal antibody targeting CD38 approved for the treatment of this malignancy. Daratumumab exerts anti-myeloma activity by different mechanisms of action as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), direct apoptosis, and immunomodulation. After GEN501 and SIRIUS trials showed efficacy of daratumumab monotherapy in heavily pretreated relapsed-refractory multiple myeloma (RRMM), in patients with at least two previous line of therapy, two phase III trials demonstrated superior overall response rate (ORR) and progression free survival (PFS) using triplets daratumumab-bortezomib-dexamethasone (DVd) vs Vd (CASTOR) or daratumumab-lenalidomide-dexamethasone (DRd) vs Rd (POLLUX) in relapsed-refractory MM patients; so these combinations have been approved and introduced in clinical practice. The ongoing phase III CANDOR is evaluating the triplet daratumumab-carfilzomib-dexamethasone (DKd) vs Kd whereas phase III APOLLO trial is exploring daratumumab-pomalidomide-dexamethasone (DPd) vs PD. Many other trials exploring daratumumab combinations in relapsed-refractory MM are ongoing, and they will provide other interesting results. In newly diagnosed transplant-eligible patients, phase III CASSIOPEIA trial found the combination daratumumab-bortezomib-thalidomide-dexamethasone (Dara-VTd) significantly improves stringent Complete Response (sCR) rate and PFS compared with VTD, whereas in the phase II GRIFFIN study, comparing daratumumab-bortezomib-lenalidomide-dexamethasone (Dara-VRD) vs VRD, sCR rate was significantly higher using quadruplet combination. Many studies are evaluating daratumumab in consolidation and maintenance therapy after autologous stem cell transplantation (ASCT). As regard patients ineligible for ASCT, a great efficacy of daratumumab-containing combinations was reported by the phase III trials ALCYONE and MAIA, exploring daratumumab-bortezomib-melphalan-prednisone (DVMP) vs VMP and daratumumab-lenalidomide-dexamethasone (DRd) vs Rd, respectively. These studies provided results never seen before in this setting. The aim of this paper is to critically review the results obtained with regimens containing daratumumab both in relapsed-refractory and in newly diagnosed MM.

Keywords: anti CD38; daratumumab; multiple myeloma; newly diagnosed multiple myeloma; relapsed refractory multiple myeloma.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
D-VTd, daratumumab, bortezomib, thalidomide, dexamethasone; D-VRd, daratumumab, bortezomib, lenelidomide, dexamethasone; wKRd_D, weekly carfilzomib, lenalidomide, dexamethasone, daratumumab; IxaRd-D, ixazomib, lenalidomide, dexamethasone, daratumumab; D-VCd and CyBorD-D, daratumumab, cyclophosphamide, bortezomib, dexamethasone. *≥ CR not available; ^MRD status not available.
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References

    1. Pulte D, Jansen L, Brenner H. Changes in long term survival after diagnosis with common hematologic malignancies in the early 21st century. Blood Cancer J (2020) 10:56. 10.1038/s41408-020-0323-4 - DOI - PMC - PubMed
    1. Attal M, Harousseau JL, Stoppa AM, Sotto JJ, Fuzibet JG, Rossi JF, et al. . A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma: Intergroup Francais du Myelome. N Engl J Med (1996) 335:91–7. 10.1056/NEJM199607113350204 - DOI - PubMed
    1. Tacchetti P, Patriarca F, Petrucci MT, Galli M, Pantani L, Dozza L, et al. . A triplet bortezomib- and immunomodulator-based therapy before and after double ASCT improves overall survival of newly diagnosed MM patients: final analysis of phase 3 GIMEMA-MMY-3006 study. HemaSphere (2018) 2(S1):abstract S105.
    1. Moreau P, Attal M, Hulin C, Arnulf B, Belhadj K, Benboubker L, et al. . Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CSSIOPEIA): a randomised, open-label, phase 3 study. Lancet (2019) 394:29–38. 10.1016/S0140-6736(19)31240-1 - DOI - PubMed
    1. Sonneveld P, Attal M, Perrot A, Hulin C, Caillot D, Facon T, et al. . Daratumumab plus bortezomib, thalidomide, and dexamethasone (D-VTd) in transplant-eligible newly diagnosed multiple myeloma (NDMM): subgroup analysis of high-risk patients in CASSIOPEIA. Clin Lymphoma Myeloma Leuk (2019) 19(10, Suppl.):e2–3. 10.1016/j.clml.2019.09.004 - DOI