Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma

Richardson, Paul G.; Jagannath, Sundar; Hussein, Mohamad A.; Berenson, James R.; Singhal, Seema; Irwin, David; Williams, Stephanie; Bensinger, William I.; Badros, Ashraf; Vescio, Robert; Kenvin, Laurie; Yu, Zhinuan; Olesnyckyj, Marta; Zeldis, Jerome B.; Knight, Robert D.; Anderson, Kenneth C.

doi:10.1182/blood-2008-12-196238

Cited by 144 publications

(76 citation statements)

References 27 publications

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“…for 21 days every 28 days (28-day cycle) in patients (n = 222) with relapsed or refractory MM (28). Twenty-five per cent of patients achieved partial reference or complete response (PR + CR) and 71% achieved stable disease or better and the median time to progression (TTP) was approximately 6 months.…”

Section: Therapeutic Trialsmentioning

confidence: 99%

Lenalidomide in the treatment of multiple myeloma: a review

2008

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Lenalidomide is an immunomodulatory drug derived from thalidomide. It was developed to maximize the anti-inflammatory and anti-neoplasic properties of thalidomide and to reduce its toxicity. The molecular mechanism of action of lenalidomide is unclear, but its therapeutic activity is mainly due to its well defined antiinflammatory, immunomodulatory, anti-proliferative and anti-angiogenic properties. In relapsed or refractory multiple myeloma (MM), lenalidomide, combined with standard dose dexamethasone, is superior to dexamethasone alone in terms of time to progression, response rate and overall survival. The most commonly reported adverse events include haematological toxicity with manageable neutropenia and thrombopenia. Lenalidomide does not trigger the limiting toxicities of thalidomide: somnolence, neuropathy and constipation. Lenalidomide, in combination with dexamethasone, is indicated for the treatment of MM patients who have received at least one prior therapy and is administered orally at the dose of 25 mg q.d. for 21 days of 28-day cycles. The drug is being investigated for the treatment of newly diagnosed MM. In this review, we summarize the pharmacokinetic, pharmacodynamic and clinical trial data on lenalidomide.

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Section: Therapeutic Trialsmentioning

confidence: 99%

Lenalidomide in the treatment of multiple myeloma: a review

2008

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“…The 2-year PFS was 30% in arm A (95% CI 22-38) and 64% in arm B (95% CI 57-71; P 5 0.002; Fig. 2B), with median PFS of 19 months (range [15][16][17][18][19][20][21][22] and 36 months (range 22-49), respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The introduction of lenalidomide has opened a new perspective because it has more potent immunomodulatory effects, and its use is not associated with peripheral neuropathy [18]. Indeed, lenalidomide maintenance after ASCT was explored in two large phase 3 trials.…”

Section: Discussionmentioning

confidence: 99%

Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression‐free survival in multiple myeloma

et al. 2012

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Despite the good response of stem cell transplant (SCT) in the treatment of multiple myeloma (MM), most patients relapse or do not achieve complete remission, suggesting that additional treatment is needed. We assessed the impact of thalidomide in maintenance after SCT in untreated patients with MM. A hundred and eight patients (<70 years old) were randomized to receive maintenance with dexamethasone (arm A; n 5 52) or dexamethasone with thalidomide (arm B; n 5 56; 200 mg daily) for 12 months or until disease progression. After a median follow-up of 27 months, an intention to treat analysis showed a 2-year progression-free survival (PFS) of 30% in arm A (95% CI 22-38) and 64% in arm B (95% CI 57-71; P 5 0.002), with median PFS of 19 months and 36 months, respectively. In patients who did not achieve at least a very good partial response, the PFS at 2 years was significantly higher when in use of thalidomide (19 vs. 59%; P 5 0.002). Overall survival at 2 years was not significantly improved (70 vs. 85% in arm A and arm B, respectively; P 5 0.27). The addition of thalidomide to dexamethasone as maintenance improved the PFS mainly in patients who did not respond to treatment after SCT. Am. J. Hematol. 87:948-952, 2012. V

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“…In addition, patients who received non-standard lenalidomide schedules had a higher incidence of grade 3/4 neutropenia than those on the standard schedule, which may reflect pre-existing neutropenia associated with prior therapies or disease activity [10,[20][21][22]. Alternatively, this may have resulted from the current management of the patient (i.e., a lenalidomide starting dose that was too high given the patient characteristics such as renal impairment).…”

Section: Discussionmentioning

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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Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma

Cited by 144 publications

References 27 publications

Lenalidomide in the treatment of multiple myeloma: a review

Lenalidomide in the treatment of multiple myeloma: a review

Thalidomide plus dexamethasone as a maintenance therapy after autologous hematopoietic stem cell transplantation improves progression‐free survival in multiple myeloma

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

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