Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial

Mateos, María Victoria; Cavo, Michèle; Bladé, Joan; Dimopoulos, Meletios A.; Suzuki, Kenshi; Jakubowiak, Andrzej; Knop, Stefan; Doyen, Chantal; Lúcio, Paulo; Nagy, Zsolt; Pour, Luděk; Cook, Mark; Grosicki, Sebastian; Crepaldi, Andre H; Liberati, Anna Marina; Campbell, Philip; Shelekhova, Tatiana; Yoon, Sung Soo; Iosava, Genadi; Fujisaki, Tomoaki; Garg, Mamta; Krevvata, Maria; Chen, Ying; Wang, Jianping; Kudva, Anupa; Ukropec, Jon; Wróblewski, Susan; Qi, Ming; Kobos, Rachel; Miguel, Jesús F. San

doi:10.1016/s0140-6736(19)32956-3

Cited by 316 publications

(307 citation statements)

References 17 publications

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“…This variation has the advantage of not affecting stem cell mobilization, and dosing is more predictable. A randomized trial found superior PFS and OS with a four‐drug regimen of Dara plus VMP compared with VMP in a randomized phase III trial, but the contribution of the fourth drug to the induction component cannot be ascertained from this trial 108 …”

Section: Treatment Of Newly Diagnosed Myelomamentioning

confidence: 93%

Multiple myeloma: 2020 update on diagnosis, risk‐stratification and management

2020

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Disease overview: Multiple myeloma accounts for approximately 10% of hematologic malignancies.Diagnosis: The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE) namely CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging (MRI). Risk stratification:The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma. Presence of any two high risk factors is considered double-hit myeloma; three or more high risk factors is triple-hit myeloma.Risk-adapted initial therapy: In transplant eligible patients, induction therapy consists of bortezomib, lenalidomide, dexamethasone (VRd) given for approximately 3-4 cycles followed by autologous stem cell transplantation (ASCT). In high-risk patients, daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) is an alternative to VRd. Selected standard risk patients can get additional cycles of induction, and delay transplant until first relapse. Patients not candidates for transplant are typically treated with VRd for approximately 8-12 cycles followed by lenalidomide; alternatively these patients can be treated with daratumumab, lenalidomide, dexamethasone (DRd).Maintenance therapy: After ASCT, standard risk patients need lenalidomide maintenance, while bortezomib-based maintenance is needed for patients with high-risk myeloma.Management of refractory disease: Most patients require a triplet regimen at relapse, with the choice of regimen varying with each successive relapse.

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Section: Treatment Of Newly Diagnosed Myelomamentioning

confidence: 93%

Multiple myeloma: 2020 update on diagnosis, risk‐stratification and management

2020

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“…The mechanism of action of daratumumab is based on the elimination of tumor cells expressing high levels of CD38 through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Recent studies have reported an increased risk of infection in multiple myeloma patients undergoing treatment with daratumumab, either as monotherapy or as combined therapy with other drugs, with some cases resulting in lethal sepsis [87][88][89][90][91][92][93]. Infections reported as drug-related adverse effects include opportunistic bacterial infections of the respiratory or urinary tracts (e.g., S. pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Haemophilus influenzae), exogenous viral infections (e.g., acute respiratory syncytial virus, human metapneumovirus and influenza A and B viruses) and viral reactivations (e.g., cytomegalovirus, herpes simplex virus and varicella-zoster virus).…”

Section: Increased Risk Of Infections In Immunotherapies Using Anti-cmentioning

confidence: 99%

Roles of CD38 in the Immune Response to Infection

Glaría

Valledor

2020

Cells

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CD38 is a multifunctional protein widely expressed in cells from the immune system and as a soluble form in biological fluids. CD38 expression is up-regulated by an array of inflammatory mediators, and it is frequently used as a cell activation marker. Studies in animal models indicate that CD38 functional expression confers protection against infection by several bacterial and parasitic pathogens. In addition, infectious complications are associated with anti-CD38 immunotherapy. Although CD38 displays receptor and enzymatic activities that contribute to the establishment of an effective immune response, recent work raises the possibility that CD38 might also enhance the immunosuppressive potential of regulatory leukocytes. This review integrates the current knowledge on the diversity of functions mediated by CD38 in the host defense to infection.

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“…Thus, our current data could provide guidance for such situations. Furthermore, the very successful results from clinical trials regarding the role of daratumumab among patients with newly diagnosed myeloma, which were completed during the present study, led to the approval of daratumumab combined with bortezomib-melphalan and prednisolone (ALCYONE study) 27 or lenalidomide (MAIA study). 28 The activity of daratumumab in the frontline is such that the response rates, duration, and, moreover, survival have improved dramatically.…”

Section: Discussionmentioning

confidence: 88%

Early Access Program Results From Turkey and a Literature Review on Daratumumab Monotherapy Among Heavily Pretreated Patients With Relapsed/Refractory Myeloma

Beksaç

Aydın

Göker

et al. 2020

Clinical Lymphoma Myeloma and Leukemia

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The present study investigated the efficacy and safety profile of daratumumab monotherapy in 42 patients with relapsed refractory multiple myeloma through a Turkish early access program. The current findings have confirmed the efficacy of daratumumab monotherapy in heavily pretreated patients with refractory multiple myeloma because of the deep and durable responses and favorable safety and tolerability profile. Background: In countries where frontline drug approval is limited to first-generation proteasome inhibitors or immunomodulatory drugs, relapses have been both more frequent and less durable. We investigated real world data on the efficacy and safety of daratumumab monotherapy among patients with relapsed refractory multiple myeloma (RRMM) from Turkey using a prospective early access program. Patients and Methods: A total of 42 patients with RRMM after a minimum of 3 previous lines of proteasome inhibitor/immunomodulatory drug-based treatments were included from 25 centers across Turkey. Daratumumab monotherapy was administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on alternate weeks (cycles 3-6), and monthly thereafter. Results: The median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7 months). The overall response rate was 45.2%, including 14 (33.3%) partial responses, 4 (9.5%) very good partial responses, and 1 (2.4%) complete response. The

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Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial

Cited by 316 publications

References 17 publications

Multiple myeloma: 2020 update on diagnosis, risk‐stratification and management

Multiple myeloma: 2020 update on diagnosis, risk‐stratification and management

Roles of CD38 in the Immune Response to Infection

Early Access Program Results From Turkey and a Literature Review on Daratumumab Monotherapy Among Heavily Pretreated Patients With Relapsed/Refractory Myeloma

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