Lenalidomide plus Dexamethasone for Relapsed or Refractory Multiple Myeloma

Dimopoulos, Meletios Α.; Spencer, Andrew; Attal, M; Prince, H. Miles; Harousseau, Jean Luc; Dmoszyńska, Anna; Miguel, Jesús F. San; Hellmann, Andrzej; Façon, Thierry; Foà, Robin; Corso, Alessandro; Masliak, Zvenyslava; Olesnyckyj, Marta; Yu, Zhinuan; Patin, John; Zeldis, Jerome B.; Knight, Robert D.

doi:10.1056/nejmoa070594

Cited by 1,329 publications

(1,136 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: 70%

“…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: 70%

Section: Discussionmentioning

confidence: 99%

Multiple myeloma: patient outcomes in real‐world practice

et al. 2016

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“…Our observations confirm the neutropenia rates reported in the European/Australian [8] and North American [9] phase 3 trials of lenalidomide and dexamethasone, as well as a recent phase 3 study [6]. Neutropenic toxicity was associated with clinical consequences: patients with grade 3/4 neutropenia had more lenalidomide exposure reductions, G-CSF use, and unplanned hospitalization relative to those without neutropenia.…”

Section: Discussionsupporting

confidence: 87%

“…Statistical analysis. Assuming an incidence of grade 3/4 neutropenia of 40% based on the literature [8,9,19], a sample size of 200 patients (allowing a 6% dropout rate) would enable 95% confidence intervals to be calculated to within a precision of 67%. As prespecified, only patients who met the eligibility criteria and who started 1 cycle of lenalidomide plus dexamethasone therapy were included in the primary analysis set.…”

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confidence: 99%

An international, multicenter, prospective, observational study of neutropenia in patients being treated with lenalidomide + dexamethasone for relapsed or relapsed/refractory multiple myeloma (RR‐MM)

et al. 2016

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Neutropenia is a well‐known dose‐limiting toxicity associated with lenalidomide plus dexamethasone treatment in patients with multiple myeloma; however, little is known about its management and associated outcomes in the real world setting. The present prospective, multicenter, observational study evaluated the incidence, management, and outcomes of grade 3/4 neutropenia in patients with relapsed or relapsed/refractory multiple myeloma who initiated treatment with lenalidomide plus dexamethasone. Of 198 patients, 62 (31%, 95% CI: 25, 38) experienced grade 3/4 neutropenia, and half of these patients experienced 3 or more events during the 12‐month observational period. Grade 3/4 neutropenia occurred throughout lenalidomide treatment, with a median time to first event of 8.8 weeks (Q1, Q3: 5.9, 17.3). In a multivariate analysis, diagnosis of relapsed and refractory disease was associated with grade 3/4 neutropenia. Lenalidomide exposure reduction, use of G‐CSF, unplanned hospitalization, and outpatient clinic visits were more common in patients who experienced grade 3/4 neutropenia than in those who did not. In conclusion, grade 3/4 neutropenia is a common toxicity and patients are at continued risk throughout treatment with lenalidomide and dexamethasone. Further efforts should be made to improve the recommendations for neutropenia management in this population. Am. J. Hematol. 91:806–811, 2016. © 2016 Wiley Periodicals, Inc.

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“…Approximately one-third of patients with relapsed refractory myeloma respond to bortezomib when used as a single agent [36]. Two large Phase III trials have shown superior TTP and OS with lenalidomide (25 mg oral days 1-21 every 28 days) plus dexamethasone compared with placebo plus dexamethasone in relapsed multiple myeloma [106,107]. Bortezomib and the immunomodulatory drugs (thalidomide or lenalidomide) can be combined effectively with each other and with other chemotherapy drugs such as cyclophosphamide and melphalan to produce highly active combination regimens.…”

Section: Treatment Of Relapsed Multiple Myelomamentioning

confidence: 99%

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

2013

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Disease overviewMultiple myeloma accounts for approximately 10% of hematologic malignancies.DiagnosisThe diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of associated end‐organ damage. In addition, the presence of 60% or more clonal plasma cells in the marrow is also considered as myeloma regardless of the presence or absence of end‐organ damage.Risk stratificationIn the absence of concurrent trisomies, patients with 17p deletion, t(14;16), and t(14;20) are considered to have high‐risk myeloma. Patients with t(4;14) translocation are considered intermediate‐risk. All others are considered as standard‐risk.Risk‐adapted initial therapyStandard‐risk patients can be treated with lenalidomide plus low‐dose dexamethasone (Rd), or a bortezomib‐containing triplet such as bortezomib, cyclophosphamide, dexamethasone (VCD). Intermediate‐risk and high‐risk patients require a bortezomib‐based triplet regimen. In eligible patients, initial therapy is given for approximately 4 months followed by autologous stem cell transplantation (ASCT). Standard‐risk patients can opt for delayed ASCT if stem cells can be cryopreserved. In patients are not candidates for transplant, initial therapy is given for approximately 12–18 months.Maintenance therapyAfter initial therapy, lenalidomide maintenance is considered for standard‐risk patients who are not in very good partial response or better, while maintenance with a bortezomib‐based regimen should be considered in pateints with intermediate or high‐risk myeloma.Management of refractory diseasePatients with indolent relapse can be treated first with two‐drug or three‐drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. Am. J. Hematol. 88:225–235, 2013. © 2013 Wiley Periodicals, Inc.

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Lenalidomide plus Dexamethasone for Relapsed or Refractory Multiple Myeloma

Abstract: Lenalidomide plus dexamethasone is more effective than high-dose dexamethasone alone in relapsed or refractory multiple myeloma. (ClinicalTrials.gov number, NCT00424047 [ClinicalTrials.gov].).

Cited by 1,329 publications

References 12 publications

Multiple myeloma: patient outcomes in real‐world practice

Multiple myeloma: patient outcomes in real‐world practice

An international, multicenter, prospective, observational study of neutropenia in patients being treated with lenalidomide + dexamethasone for relapsed or relapsed/refractory multiple myeloma (RR‐MM)

Multiple myeloma: 2013 update on diagnosis, risk‐stratification, and management

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