Activity of Melflufen in RR MM Patients with Extramedullary Disease in the Phase 2 HORIZON Study (OP-106): Promising Results in a High-Risk Population

Richardson, Paul G.; Mateos, María‐Victoria; Rodríguez‐Otero, Paula; Norkin, Maxim; Larocca, Alessandra; Hassoun, Hani; Alegre, Adrián; Paner, Agne; Leleu, Xavier; Maisel, Christopher; Mazumder, Amitabha; Harmenberg, Johan; Byrne, Catriona; Zubair, Hanan; Thuresson, Sara; Bladé, Joan

doi:10.1016/j.clml.2019.09.582

Cited by 2 publications

(4 citation statements)

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“…96 Of interest, melflufen has resulted in a significant response rate in both EMD and PS disease, 97 with an overall response (PR or better) of 23% (13/55 patients) and similar duration of response between patients with or without plasmacytomas. 97 Selinexor and dexamethasone showed a response rate of 31% (five of 16). However, in this study only 16 out of 27 patients with plasmacytomas were available for response evaluation.…”

Section: General Considerationsmentioning

confidence: 99%

“…The initial results with melflufen are encouraging and melflufen-based regimens could be of help. 97 For patients with CNS involvement craniospinal radiation, triple intrathecal chemotherapy (glucocorticoids, methotrexate and cytarabine) and systemic IMiD-based therapy is recommended. 43 With the limitations of most standard approaches in the control of EMD disease, newer immunotherapeutic strategies such as toxin immunoconjugate MoAbs, bi-specific antibodies against CD3 and B-cell maturation antigen (BCMA) recruiting endogenous T cells and autologous chimeric antigen receptor (CAR) T cells, mainly directed against BCMA present on the malignant PC surface are promising.…”

Section: Treatment At Relapsementioning

confidence: 99%

“…Also, the PFS was also longer with Isa‐Pd compared with Pd (4·57 vs. 1·56 months) 96 . Of interest, melflufen has resulted in a significant response rate in both EMD and PS disease, 97 with an overall response (PR or better) of 23% (13/55 patients) and similar duration of response between patients with or without plasmacytomas 97 . Selinexor and dexamethasone showed a response rate of 31% (five of 16).…”

Section: Treatment Approachmentioning

confidence: 99%

“…Alternatively, in patients initially treated with IMiD‐based therapy, rescue with proteasome inhibitor‐based regimens maybe effective. The initial results with melflufen are encouraging and melflufen‐based regimens could be of help 97 . For patients with CNS involvement craniospinal radiation, triple intrathecal chemotherapy (glucocorticoids, methotrexate and cytarabine) and systemic IMiD‐based therapy is recommended 43 .…”

Section: Treatment Approachmentioning

confidence: 99%

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Expert review on soft‐tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations

et al. 2021

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In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1Á7% to 4Á5% and 7% to 34Á4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.

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Section: General Considerationsmentioning

confidence: 99%

Section: Treatment At Relapsementioning

confidence: 99%