Lenalidomide

ArticlesLactation Safety InformationNew Medicines ·
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Articles

Lactation Safety Information

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No published evidence of safety
Serious adverse effects reported in adults
22 September 2020

New Medicines

RevlimidMultiple myeloma (MM) - first-line in combination with bortezomib and dexamethasone in patients who are previously untreated and are not eligible for stem cell transplant

Information

Revlimid
Licence extension / variation
Celgene
Celgene

Development and Regulatory status

Launched
Launched
Phase III Clinical Trials
May 2019
May 19Approved in EU [8].
Mar 19Alteration to indications recommended for EU approval by CHMP - the amended indication is "as combination therapy with dexamethasone, or bortezomib and dexamethasone, or melphalan and prednisone (see section 4.2) is indicated for the treatment of adult patients with previously untreated multiple myeloma who are not eligible for transplant." The amendment is to specify the combination therapy options [6].
Oct 17Will be filed via the EU centralised procedure [2].

Category

Structural analogue of thalidomide
Multiple myeloma is the second most common haematological cancer. It is responsible for 15-20% of deaths from haematological cancer and about 2% of all deaths from cancer. The incidence in Europe is 4.5-6.0 per 100,000/year with a mortality rate of 4.1 per 100,000/year [1].
Multiple myeloma (MM) - first-line in combination with bortezomib and dexamethasone in patients who are previously untreated and are not eligible for stem cell transplant
Oral

Further information

Yes
June 2019

Trial or other data

Dec 18PIII Myeloma XI (NCT01554852; n=1917) is published in The Lancet. The authors reported that maintenance with lenalidomide improved PFS vs observation (39 vs 20 months; HR 0.46; p<0.0001), but did not improve overall survival in the ITT analysis of the whole trial population (3-year overall survival: 78.6% vs 75.8%, respectively) [5].
Sep 18PIII study to evaluate the clinical benefit from the drug combination lenalidomide plus bortezomib plus dexamethasone (RVD) without immediate high-dose therapy (HDT) followed by lenalidomide maintenance (Arm A) versus RVD plus HDT and peripheral blood stem cell transplant (PBSCT) followed by lenalidomide maintenance (Arm B) is due to complete (NCT01191060) [5].
Sep 17PIII GEM2012MENOS65 study has completed (NCT01916252). It is measuring PFS in patients receiving one of two pre-transplant conditioning regimens (BUMEL versus. MEL-200). A total of 460 patients will be enrolled. During the treatment period, eligible patients will be included in the study and given six cycles of induction treatment with bortezomib/ lenalidomide / dexamethasone (VRD-GEM). Each cycle will last 28 days, during which SC bortezomib will be administered on days 1, 4, 8 and 11, oral lenalidomide on days 1-21 of each cycle, and oral dexamethasone on days 1-4 and 9-12 of the cycle. After the first three induction cycles, and in the absence of progression or unacceptable toxicity, peripheral blood hematopoietic stem cells will be mobilized and collected using G-CSF for later autologous transplantation. Patients will be randomized in a 1:1 allocation ratio to receive conditioning treatment with MEL-200 versus BUMEL. Three months after transplantation, patients will receive two cycles of consolidation treatment with VRD-GEM at the same doses administered during induction treatment [4].
Dec 15PIII SWOG-S0777 results show addition of bortezomib to lenalidomide and dexamethasone significantly improved remission rates and extended the duration of disease control in newly diagnosed patients with multiple myeloma when compared with lenalidomide plus dexamethasone [3].
Mar 08PIII trial evaluating safety and efficacy of triple regimen of lenalidomide, dexamethasone plus bortezomib starts (SWOG-S0777; NCT00644228). The trial will enrol 471 patients in the US [2].

Evidence based evaluations

RevlimidFollicular lymphoma in previously treated adults (grade 1 – 3a) - in combination with rituximab

Information

Revlimid
Licence extension / variation
Celgene
Celgene

Development and Regulatory status

Launched
Launched
Launched
December 2019
Dec 19The EC has approved a new indication for Revlimid (lenalidomide), in combination with rituximab (anti-CD20 antibody), for the treatment of adult patients with previously treated follicular lymphoma [13].
Nov 19EU positive opinion for a new indication of in combination with rituximab for treatment of adults with previously treated follicular lymphoma (Grade 1 – 3a) [12].
May 19Marketing Authorisation Application for lenalidomide in combination with rituximab is currently under review by the European Medicines Agency for the treatment of relapsed/refractory FL and MZL [11].
May 19Having been granted Priority Review designation, the US FDA approved the combination of lenalidomide (Revlimid) with rituximab (code name R2) for the treatment of adult patients with previously treated follicular lymphoma (FL) or marginal zone lymphoma (MZL) [9,10].
Nov 15Celgene pipeline lists lenalidomide as in PIII development for relapsed/refractory follicular lymphoma [4].

Category

Analogue of thalidomide
Follicular lymphoma affects ~ 2.2 in 10,000 people in the EU, equivalent to a total of around 112,000 people [3].
Follicular lymphoma in previously treated adults (grade 1 – 3a) - in combination with rituximab
Oral

Further information

Yes
April 2020

Trial or other data

Mar 19Results of PIII AUGMENT (n=358) are published in the Journal of Clinical Oncology; lenalidomide improved efficacy of rituximab. Progression-free survival was significantly improved for the lenalidomide + rituximab vs. placebo + rituximab (HR 0.46, p <0.001). Median duration of 39.4 months vs. 14.1 months, respectively [8].
Nov 18Results of AUGMENT (NCT01938001) posted on the American Society of Hematology website. This was a multicentre, double-blind, randomised PIII study (n=358) of lenalidomide + rituximab (R2) vs rituximab/placebo (control) in patients with FL grade 1-3a or MZL previously treated with ≥ 1 prior systemic therapy with documented relapsed or refractory disease but not refractory to rituximab. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rate (ORR), complete response (CR), duration of response (DOR), time-to-next antilymphoma treatment (TTNLT), overall survival (OS), and safety. At median follow-up of 28.3 months, the study met its primary endpoint of PFS with HR = 0.46 (95% CI, 0.34 - 0.62; p<0.0001). Median PFS was 39.4 months for R2 vs 14.1 months for control [7].
Dec 17PIII MAGNIFY (NCT01996865) study is still recruiting pts; date of collection of primary outcome data unchanged [6].
Nov 16PIII MAGNIFY (NCT01996865) study is recruiting pts; collection of primary outcome data expected to complete Feb 21 [5].
Mar 14PIII MAGNIFY has yet to start recruiting pts [2].
Nov 13NCT01996865 (MAGNIFY) is a PIII multicenter, randomized (stratified by histology, lines of anti-lymphoma therapy and age), open label study in 500 subjects with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL) or mantle cell lymphoma (MZL). All subjects will receive 12 Cycles of lenalidomide + rituximab induction therapy. The study is designed to compare 2 maintenance regimens: lenalidomide + rituximab combination therapy (for 18 Cycles) followed by lenalidomide single-agent maintenance (Arm A) or rituximab single-agent maintenance (for 18 Cycles; Arm B, control). The primary outcome is PFS. The study starts Feb 14 and is due to complete Oct 2022 [1]

Evidence based evaluations