Elotuzumab, lenalidomide, and dexamethasone as salvage therapy for patients with multiple myeloma: Italian, multicenter, retrospective clinical experience with 300 cases outside of controlled clinical trials

Gentile, Massimo; Specchia, Giorgina; Derudas, Daniele; Galli, Mónica; Botta, Cirino; Rocco, Stefano; Conticello, Concetta; Califano, Catello; Giuliani, Nicola; Mangiacavalli, Silvia; Attingenti, Enrico; Lombardo, Alessandra; Brunori, Marino; Rossi, Elena; Antonioli, Elisabetta; Ria, Roberto; Zambello, Renato; Renzo, Nicola Di; Mele, Giuseppe; Marcacci, Gianpaolo; Musto, Pellegrino; Capalbo, Silvana; Cascavilla, Nicola; Cerchione, Claudio; Belotti, Angelo; Criscuolo, Clelia; Uccello, Giuseppina; Curci, Paola; Vigna, Ernesto; Fraticelli, Vincenzo; Vincelli, Donatella; Bonalumi, Angela; Siniscalchi, Agostina; Stocchi, Raffaella; Martino, Massimo; Ballanti, Stelvio; Gangemi, Dominella; Gagliardi, Alfredo; Gamberi, Barbara; Pompa, Alessandra; Recchia, Anna Grazia; Tripepi, Giovanni; Pitino, Annalisa; Frigeri, Ferdinando; Consoli, Ugo; Bringhen, Sara; Zamagni, Elena; Stefano, Valerio De; Raimondo, Francesco Di; Palmieri, Salvatore; Petrucci, Maria Teresa; Offidani, Massimo; Boccadoro, Mario; Cavo, Michèle; Morabito, Fortunato

doi:10.3324/haematol.2019.241513

Cited by 22 publications

(31 citation statements)

References 15 publications

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“…A graft vs. myeloma effect has been shown by the differences in post-allogeneic stem cell transplant relapse rates based on the inherited repertoire of KIR genes expressed by donor NK cells, indicating a role for NK cell-mediated suppression of relapse [22,24]. Lastly, NK cells mediate ADCC against myeloma cells in vitro and in vivo, thus enhancing the anti-MM activity of current therapies, which includes mAbs such as the anti-CD38 daratumumab and isatuximab [45] and the anti-SLAMF7 elotuzumab (Figure 2) [70,71].…”

Section: Nkmentioning

confidence: 99%

Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities

Botta

Mendicino

Martino

et al. 2021

Cancers

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Multiple myeloma (MM) is the second most common hematologic malignancy, characterized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often through an intermediate phase known as “smoldering” MM (sMM). Interestingly, while many genomic alterations (translocation, deletions, mutations) are usually found at early stages, they are not sufficient (alone) to determine disease evolution. The latter, indeed, relies on significant “epigenetic” alterations of different normal cell populations within the bone marrow (BM) niche, including the “evasion” from immune-system control. Additionally, MM cells could “educate” the BM immune microenvironment (BM-IM) towards a pro-inflammatory and immunosuppressive phenotype, which ultimately leads to disease evolution, drug resistance, and patients’ worse outcome. Indeed, it is not a case that the most important drugs for the treatment of MM include immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide) and monoclonal antibodies (daratumumab, isatuximab, and elotuzumab). On these bases, in this review, we describe the most recent advances in the comprehension of the role of the different cells composing the BM-IM, and we discuss the potential molecular targets, which could represent new opportunities to improve current treatment strategies for MM patients.

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Section: Nkmentioning

confidence: 99%

Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities

Botta

Mendicino

Martino

et al. 2021

Cancers

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“…12 Similarly, the addition of elotuzumab to Rd reduced the risk of progression by 30%, with a gain of 4.5 progression-free months compared with the control arm. 14 In this current study, in the lack of a randomized KRd vs. EloRd trial, and with the well-known limitations and susceptibility to the bias of real-life suggestions, 17 we weighed the relative usefulness of one triplet over the other, comparing a multicenter retrospective EloRd cohort 18 with four multicenter retrospective KRd cohorts, [19][20][21][22] all including RRMM cases treated outside of clinical trials. This current clinical practice study's overall results demonstrate that KRd therapy offers a superior outcome than EloRd.…”

Section: Significance Statementmentioning

confidence: 99%

Adjusted comparison between elotuzumab and carfilzomib in combination with lenalidomide and dexamethasone as salvage therapy for multiple myeloma patients

Morabito

Zamagni

Conticello

et al. 2021

European J of Haematology

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The therapeutic algorithm of multiple myeloma (MM) patients has noticeably changed in the last few years, becoming increasingly complex in choosing the subsequent best therapy for relapsed and refractory MM (RRMM) patients. [1][2][3][4][5] In this setting, optimal treatment selection warrants unique concerns associated with the patient-and disease-related factors. [3][4][5] Nevertheless, the triplet regimens characterize the new standard of care for RRMM since they produce more profound responses and result in prolonged progression-free survival (PFS) compared with doublet therapies. 6,7 Irrespective of the more recent combinations, [8][9][10][11] the endorsement in favor of

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“…The phase 3 ELOQUENT-2 trial was an international, open-label, randomized trial comparing ERd ( n = 321) to Rd alone ( n = 325) in RRMM and showed that the addition of Elo provided an 18% reduction in the risk of death compared to Rd alone [ 51 , 52 ]. In a “real world” experience of ERd in RRMM consisting of a predominantly len naïve population, the regimen was safe with efficacy with a median PFS of 17.6 months and was well tolerated in elderly patients ≥ 75 years of age [ 53 ]. This regimen was FDA approved in 2015 for the treatment of patients with RRMM following two to three prior therapies.…”

Section: Monoclonal Antibodies Are Highly Efficient In the Relapsed Settingmentioning

confidence: 99%

The Role of Monoclonal Antibodies in the Era of Bi-Specifics Antibodies and CAR T Cell Therapy in Multiple Myeloma

Mohan

Maatman

Schinke

2021

Cancers

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Multiple myeloma (MM) remains largely incurable despite enormous improvement in the outcome of patients [1]. Over the past decade, we have witnessed the “era of monoclonal antibody (moAb)”, setting new benchmarks in clinical outcomes for relapsed and newly diagnosed MM. Due to their excellent efficacy and relative safe toxicity profile, moAbs in combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have become the new backbone of upfront anti-MM therapy. Yet, most patients will eventually relapse and patients who become refractory to IMiDs, PIs and moAbs have a dismal outcome. Emerging T-cell directing therapies, such as bispecific antibody (bsAb) and chimeric antigen receptor T cells (CAR T) have shown unprecedented responses and outcomes in these heavily pretreated and treatment-refractory patients. Their clinical efficacy combined with high tolerability will likely lead to the use of these agents earlier in the treatment course and there is great enthusiasm that a combination of T cell directed therapy with moAbs can lead to long duration remission in the near future, possibly even without the need of high dose chemotherapy and stem cell transplantation. Herein, we summarize the role of naked moAbs in MM in the context of newer immunotherapeutic agents like bsAb and CAR T therapy.

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Elotuzumab, lenalidomide, and dexamethasone as salvage therapy for patients with multiple myeloma: Italian, multicenter, retrospective clinical experience with 300 cases outside of controlled clinical trials

Cited by 22 publications

References 15 publications

Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities

Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities

Adjusted comparison between elotuzumab and carfilzomib in combination with lenalidomide and dexamethasone as salvage therapy for multiple myeloma patients

The Role of Monoclonal Antibodies in the Era of Bi-Specifics Antibodies and CAR T Cell Therapy in Multiple Myeloma

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