Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial

Miguel, Jesús F. San; Weisel, Katja; Moreau, Philippe; Lacy, Martha Q.; Song, Kijoung; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrián; Chen, Christopher; Cavo, Michèle; Garderet, Laurent; Ivanova, Valentina; Martínez‐López, Joaquín; Belch, Andrew R.; Palumbo, Antônio; Schey, Steve; Sonneveld, Pieter; Yu, Xiaoyan; Sternås, Lars; Jacques, Christian; Zaki, Mohamed H.; Dimopoulos, Meletios Α.

doi:10.1016/s1470-2045(13)70380-2

Cited by 723 publications

(823 citation statements)

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“…Furthermore, in accordance with published reports (van Rhee et al , 2014), patients who had undergone SCT were more likely to achieve CR than those who had not. Moreover, efficacy outcomes were broadly similar to those seen in clinical trials (Singhal et al , 1999; Richardson et al , 2005; Dimopoulos et al , 2007; Weber et al , 2007; San Miguel et al , 2013). Achievement of CR or VGPR was also associated with a greater likelihood of receiving a further line of treatment.…”

Section: Discussionsupporting

confidence: 69%

“…Given the availability of agents that are effective in relapsed and refractory MM (Singhal et al , 1999; Richardson et al , 2005; Dimopoulos et al , 2007; Weber et al , 2007; Offidani et al , 2013; San Miguel et al , 2013; San‐Miguel et al , 2014; Stewart et al , 2015), it is perhaps surprising that relatively few patients receive multiple lines of therapy. About a quarter of patients completed fourth‐line treatment as planned, and 38% of patients ended fourth‐line treatment in remission, suggesting that patients do benefit from receiving treatment at this later stage; however, very few reach fifth‐line treatment (1%).…”

Section: Discussionmentioning

confidence: 99%

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Multiple myeloma: patient outcomes in real‐world practice

et al. 2016

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SummaryWith increasing number of therapies available for the treatment of multiple myeloma, it is timely to examine the course of patients' journeys. We investigated patient characteristics, treatment durations and outcomes, and symptom burden across the treatment pathway in Belgium, France, Germany, Italy, Spain, Switzerland and the UK. In total, 435 physicians retrospectively reviewed 4997 patient charts. Profiles of patients diagnosed with multiple myeloma during the last 12 months were similar across countries; bone pain was the most common presentation. Median duration of first‐line therapy was 6 months, followed by a median treatment‐free interval of 10 months; both these decreased with increasing lines of therapy, as did time to progression. Depth of response, as assessed by the treating physician, also decreased with each additional line of therapy: 74% of patients achieved at least a very good partial response at first line, compared with only 11% at fifth line. Deeper responses were associated with longer time to progression, although these were physician‐judged. Toxicities and co‐morbidities increased with later treatment lines, and were more likely to have led to discontinuation of treatment. These real‐world data provide an insight into patient outcomes and treatment decisions being made in clinical practice.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Multiple myeloma: patient outcomes in real‐world practice

et al. 2016

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“…This may be particularly relevant in myeloma as new therapies such as carfilzomib and pomalidomide continue to provide additional therapeutic options for patients with relapsed/refractory disease. 14,15 In MM-015, effective post-second-line therapy may have contributed to the generally excellent, but similar, OS in each treatment group. It should be noted that the MM-015 trial was neither designed nor powered to evaluate OS, and crossover was encouraged by providing the option to all patients to participate in an open-label haematologica 2015; 100:e329 LETTERS TO THE EDITOR © F e r r a t a S t o r t i F o u n d a t i o n extension phase of lenalidomide therapy at relapse.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O Nmentioning

confidence: 99%

Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point

et al. 2015

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“…12 A phase 3 study of pomalidomide plus low-dose dexamethasone vs high-dose dexamethasone alone demonstrated a significant benefit to OS, PFS, and overall response rate (ORR). 13 Notably, subgroup analyses demonstrated a benefit to OS and PFS in lenalidomide-refractory patients treated with pomalidomide plus low-dose dexamethasone vs high-dose dexamethasone. 13 In addition, single-agent pomalidomide has been shown to upregulate CD38 expression on MM cell lines, 14 and pretreatment of patientderived effector cells with an IMiD (lenalidomide) has been shown to synergistically enhance daratumumab-mediated antibody-dependent cell-mediated cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

“…13 Notably, subgroup analyses demonstrated a benefit to OS and PFS in lenalidomide-refractory patients treated with pomalidomide plus low-dose dexamethasone vs high-dose dexamethasone. 13 In addition, single-agent pomalidomide has been shown to upregulate CD38 expression on MM cell lines, 14 and pretreatment of patientderived effector cells with an IMiD (lenalidomide) has been shown to synergistically enhance daratumumab-mediated antibody-dependent cell-mediated cytotoxicity. 15 Finally, pom-dex has demonstrated immune modulation, via activation of T cells, that correlated with clinical response, 16 which could potentially complement the immunomodulatory effects demonstrated by daratumumab.…”

Section: Introductionmentioning

confidence: 99%

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma

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Suvannasankha

Fay

et al. 2017

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• No new safety signals were observed with daratumumab plus pomalidomide and dexamethasone, except for increased neutropenia.• Daratumumab plus pomalidomide and dexamethasone induced rapid, deep, and durable responses in heavily treated patients with multiple myeloma.Daratumumab plus pomalidomide and dexamethasone (pom-dex) was evaluated in patients with relapsed/refractory multiple myeloma with ‡2 prior lines of therapy who were refractory to their last treatment. Patients received daratumumab 16 mg/kg at the recommended dosing schedule, pomalidomide 4 mg daily for 21 days of each 28-day cycle, and dexamethasone 40 mg weekly. Safety was the primary end point. Overall response rate (ORR) and minimal residual disease (MRD) by next-generation sequencing were secondary end points. Patients (N 5 103) received a median (range) of 4 (1-13) prior therapies; 76% received ‡3 prior therapies. The safety profile of daratumumab plus pomdex was similar to that of pom-dex alone, with the exception of daratumumab-specific infusion-related reactions (50%) and a higher incidence of neutropenia, although without an increase in infection rate. Common grade ‡3 adverse events were neutropenia (78%), anemia (28%), and leukopenia (24%). ORR was 60% and was generally consistent across subgroups (58% in double-refractory patients). Among patients with a complete response or better, 29% were MRD negative at a threshold of 10 25 . Among the 62 responders, median duration of response was not estimable (NE; 95% confidence interval [CI], 13.6-NE). At a median follow-up of 13.1 months, the median progression-free survival was 8.8 (95% CI, 4.6-15.4) months and median overall survival was 17.5 (95% CI, 13.3-NE) months. The estimated 12-month survival rate was 66% (95% CI, 55.6-74.8). Aside from increased neutropenia, the safety profile of daratumumab plus pom-dex was consistent with that of the individual therapies. Deep, durable responses were observed in heavily treated patients. The study was registered at www.clinicaltrials.gov as #NCT01998971. (Blood. 2017;130(8):974-981)

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Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial

Cited by 723 publications

References 28 publications

Multiple myeloma: patient outcomes in real‐world practice

Multiple myeloma: patient outcomes in real‐world practice

Impact of maintenance therapy on subsequent treatment in patients with newly diagnosed multiple myeloma: use of "progression-free survival 2" as a clinical trial end-point

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma

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