Phase I safety data of lenalidomide, bortezomib, dexamethasone, and elotuzumab as induction therapy for newly diagnosed symptomatic multiple myeloma: SWOG S1211

Usmani, Saad Z.; Sexton, Rachael; Ailawadhi, Sikander; Shah, Jatin J.; Valent, Jason; Rosenzweig, Michael; Lipe, Brea; Zonder, Jeffrey A.; Fredette, Sandi; Durie, Brian G.M.; Hoering, Antje; Bartlett, Blake; Orłowski, Robert Z.

doi:10.1038/bcj.2015.62

Cited by 33 publications

(13 citation statements)

References 6 publications

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“…Several phase III studies are evaluating KRD as an induction based on encouraging earlier pilot trials (19, 53), and the ability of this regimen to induce high rates of MRD-negativity make it a very attractive option as well. Also of note, monoclonal antibodies have already been added to RVD as part of induction (54), and it is likely that such four-drug regimens will be in use in the future, especially for patients with a good performance status.…”

Section: Optimal Current Use Of Novel Agents In Myelomamentioning

confidence: 99%

Integration of Novel Agents into the Care of Patients with Multiple Myeloma

Orłowski

Lonial

2016

Clinical Cancer Research

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The pace of therapeutic drug development in multiple myeloma has reached unprecedented levels, with five regulatory approvals for relapsed and/or refractory disease of either new drugs or new regimens in 2015, and one already in 2016, while still others are anticipated. This has provided a wide array of options to be considered by patients and their healthcare providers in the event of relapse after, or progression on front-line therapy. Most of these agents are currently being evaluated in earlier patient populations, including as parts of induction, consolidation, and maintenance therapy approaches, where their benefits may be even greater. Moreover, additional randomized studies have been completed with our previous stable of novel agents that inform their use in these settings as well. In the current contribution to this CCR Focus on multiple myeloma, we will present an overview of some of the key recent data that have supported the addition of these new therapeutics to our armamentarium against multiple myeloma. Also, we will provide some guidelines about possible best practices in applying these regimens, and attempt to extrapolate how they will be used as parts of our future standards of care.

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Section: Optimal Current Use Of Novel Agents In Myelomamentioning

confidence: 99%

Integration of Novel Agents into the Care of Patients with Multiple Myeloma

Orłowski

Lonial

2016

Clinical Cancer Research

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“…A phase 1 study, S1211, has also reported on the safety of maintenance therapy in patients with newly diagnosed high risk myeloma. 39 The trial examined the use of lenalidomide, bortezomib, elotuzumab and dexamethasone as maintenance therapy, and suggests little additive toxicity with the incorporation of elotuzumab to lenalidomide and bortezomib based therapy. The phase II results of this trial are upcoming.…”

Section: Resultsmentioning

confidence: 99%

The role of maintenance therapy in multiple myeloma

Lipe

Vukas

Mıkhael

2016

Blood Cancer Journal

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Multiple myeloma is the second most common type of blood cancer and remains incurable despite advances in therapy. Current therapy for multiple myeloma includes a phased-approach, often consisting of initial induction therapy, consolidation and maintenance therapy. With an ever-growing landscape of treatment options, the approach to optimal therapy has become increasingly complex. Specifically, controversy surrounds the optimal use and duration of maintenance therapy. We conducted a comprehensive literature search to analyze the most current literature and to provide recommendations for maintenance therapy in multiple myeloma.

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“…Moreover, the addition of elotuzumab to bortezomib, lenalidomide, and dexamethasone (LBd) is feasible without major additive AEs beyond what is already known about LBd, as demonstrated in SWOGS1211 trial. 101 However, the efficacy of elotuzumab in combination with LBd needs to be studied.…”

Section: Optimal Use Of Eld For the Treatment Of Rrmmmentioning

confidence: 99%

Elotuzumab for the Treatment of Relapsed or Refractory Multiple Myeloma, With Special Reference to Its Modes of Action and Slamf7 Signaling

Yoshida¹,

Matsumoto²,

Shimura³

et al. 2018

Mediterr J Hematol Infect Dis

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Elotuzumab, targeting signaling lymphocytic activation molecule family 7 (SLAMF7), has been approved in combination with lenalidomide and dexamethasone (ELd) for relapsed/refractory multiple myeloma (MM) based on the findings of the phase III randomized trial ELOQUENT-2 (NCT01239797). Four-year follow-up analyses of ELOQUENT-2 have demonstrated that progression-free survival was 21% in ELd versus 14% in Ld. Elotuzumab binds a unique epitope on the membrane IgC2 domain of SLAMF7, exhibiting a dual mechanism of action: natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and enhancement of NK cell activity. The ADCC is mediated through engagement between Fc portion of elotuzumab and FcgRIIIa/CD16 on NK cells. Enhanced NK cell cytotoxicity results from phosphorylation of the immunoreceptor tyrosine-based switch motif (ITSM) that is induced via elotuzumab binding and recruits the SLAM-associated adaptor protein EAT-2. The coupling of EAT-2 to the phospholipase Cg enzymes SH2 domain leads to enhanced Ca2+ influx and MAPK/Erk pathway activation, resulting in granule polarization and enhanced exocytosis in NK cells. Elotuzumab does not stimulate the proliferation of MM cells due to a lack of EAT-2. The inhibitory effects of elotuzumab on MM cell growth are not induced by the lack of CD45, even though SHP-2, SHP-1, SHIP-1, and Csk may be recruited to phosphorylated ITSM of SLAMF7. ELd improves PFS in patients with high-risk cytogenetics, i.e. t(4;14), del(17p), and 1q21 gain/amplification. Since the immune state is paralytic in advanced MM, the efficacy of ELd with minimal toxicity may bring forward for consideration of its use in the early stages of the disease.

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Phase I safety data of lenalidomide, bortezomib, dexamethasone, and elotuzumab as induction therapy for newly diagnosed symptomatic multiple myeloma: SWOG S1211

Cited by 33 publications

References 6 publications

Integration of Novel Agents into the Care of Patients with Multiple Myeloma

Integration of Novel Agents into the Care of Patients with Multiple Myeloma

The role of maintenance therapy in multiple myeloma

Elotuzumab for the Treatment of Relapsed or Refractory Multiple Myeloma, With Special Reference to Its Modes of Action and Slamf7 Signaling

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