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Lenalidomide is a thalidomide descendant that glues the proteins IKZF1 and IKZF3 to cereblon so the cell destroys them, killing plasma cells and rousing T cells. It is the backbone of myeloma treatment and maintenance, also used in mantle cell and follicular lymphoma, and generic since 2022.
Approved 2006 (myeloma with dexamethasone), 2017 (post-transplant maintenance), plus MDS del(5q), mantle cell and follicular lymphoma (R2). Generic since 2022. Degrades IKZF1/IKZF3 via cereblon, killing plasma cells and co-stimulating T cells; the basis for CELMoDs and molecular-glue degraders generally.
Binds cereblon (CRBN) in the CRL4 E3 ligase, recruiting Ikaros and Aiolos for ubiquitination and degradation; downregulates IRF4/MYC; enhances IL-2 and T/NK activity. Connects to IKZF1 (Ikaros) and IKZF3 (Aiolos).
1.Lenalidomide binds cereblon in the CRL4 ubiquitin ligase
Oral, self-administered, so it is a Part D drug: covered through a stand-alone Part D plan or Medicare Advantage drug benefit, usually on the specialty tier with 25 to 33% coinsurance until the annual cap ($2,000 in 2025, $2,100 in 2026). Generic lenalidomide entered the US in March 2022 under volume-limited licences and became fully generic in January 2026; Part D plans increasingly prefer the generic. Dispensed only through the REMS.
Covered for FDA-labelled and NCCN-listed uses, but almost always behind prior authorisation confirming diagnosis, biomarker and line of therapy; dispensed through a specialty pharmacy. Plans now require the generic where available.
Part D out-of-pocket capped at $2,000 (2025) / $2,100 (2026). Medicare patients cannot use manufacturer co-pay cards; charity funds (PAN, HealthWell, CancerCare) and the Extra Help subsidy are the routes.
Sources: Medicare.gov: Drug coverage (Part D) · Medicare.gov: Costs for Medicare drug coverage (annual out-of-pocket cap). Not medical or financial advice; verify with your plan.
Sources: NICE TA171 · SMC advice: lenalidomide. Funding decisions are indication-specific and change monthly; verify with NICE and your treating team.
| Date | Deal | Type | Upfront | Total | Source |
|---|---|---|---|---|---|
| 2019-01-03 | Celgene to Bristol Myers Squibb Revlimid, Pomalyst, bb2121 (Abecma), liso-cel (Breyanzi) and the Celgene pipeline | Acquisition | not disclosed | $74bn (plus a contingent value right) | source |
MDS del(5q)
Myeloma with dexamethasone
First generics launch (volume-limited)
| Region | Year | Indication |
|---|---|---|
| US | 2005 | Transfusion-dependent anaemia in low-risk MDS with del(5q) |
| US | 2006 | Relapsed myeloma with dexamethasone |
| US | 2015 | Newly diagnosed myeloma with dexamethasone |
| US | 2017 | Maintenance after autologous transplant |
| Adverse event | Any grade | Grade 3+ |
|---|---|---|
| Neutropenia MM-009/010 with dexamethasone | - | 35% |
| Venous thromboembolism without prophylaxis | 12% | - |
| Second primary malignancy maintenance after melphalan (CALGB 100104, 7-8% vs 3%) | 7% | - |
Events listed without rates were not read from a primary source; see the label. Blank cells mean the figure was not sourced, not that it is zero.
| Country | Reimbursement | List price | Assistance |
|---|---|---|---|
| United Statesgeneric | - | ~$20,000 per month (brand, 2022); generics volume-limited until 2026 | - |
List prices are manufacturer or Medicare figures where publicly disclosed; net prices after rebates are usually lower. Reimbursement changes; check the payer.
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A new combination for relapsed or refractory follicular lymphoma that adds a CD19-directed antibody to the established lenalidomide and rituximab pairing, with the largest progression-free survival hazard ratio reported in the setting.
The evidence behind the United States approval of brentuximab vedotin with lenalidomide and a rituximab product for relapsed or refractory diffuse large B-cell lymphoma after two or more lines in patients not eligible for an autologous transplant or CAR-T. It is also the first demonstration that a CD30-directed conjugate helps in a disease where CD30 expression is variable.
CEPHEUS extends the quadruplet standard to patients who are not going to transplant, closing the gap between transplant-eligible and ineligible populations. It is also one of the first phase 3 trials to be designed around MRD-negativity as the primary endpoint, which could shorten future myeloma trials by years. Frailer patients still need dose-adapted approaches.
PERSEUS, with the earlier GRIFFIN and CASSIOPEIA trials, made a four-drug daratumumab quadruplet the standard for fit patients heading to transplant. It also introduced MRD-directed stopping of the antibody, a step towards treatment that is deep but not indefinite. Whether transplant itself remains necessary on top of a quadruplet is now the open question.
Lenalidomide showed that intervening before symptoms can delay end-organ damage, supporting later trials such as AQUILA, but tolerability limits its use as a single agent.
Lenalidomide-rituximab is approved for relapsed follicular and marginal zone lymphoma and is a standard chemotherapy-free choice, though marginal zone-specific evidence is thinner.
MAIA made a daratumumab-based triplet the standard first treatment for older or frail myeloma patients, replacing Rd alone. It proved an anti-CD38 antibody could improve survival, not just delay progression, when used up front. Quadruplets built on this backbone are now being tested in the same population.
Rituximab-lenalidomide is an accepted chemotherapy-free first-line alternative for follicular lymphoma, chosen on toxicity profile and patient preference rather than efficacy.
Query for this drug: (TITLE:"Lenalidomide" OR ABSTRACT:"Lenalidomide" OR TITLE:"Revlimid" OR ABSTRACT:"Revlimid") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Lenalidomide, not a curated reading list.
Shares A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Mul, DRAMMATIC, A Study of Daratumumab, A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving T Cell Engaging Bi/Tri-spe.
Shares Kenneth C. Anderson, A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Mul, Phase II Study of QLS32015 Combination Therapy in the Treatment of Multiple Myeloma, IFM 2009: lenalidomide, bortezomib and dexamethasone with or without upfront transplantation for myeloma.
Shares A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma, RELEVANCE: rituximab plus lenalidomide in advanced untreated follicular lymphoma, A Study of Rocbrutinib in Participants With Relapse or Refractory Non-GCB Diffuse Large B-Cell Lymphoma, Study of Acalabrutinib Alone or in Combination Therapy in Subjects With B-cell Non-Hodgkin Lymphoma.
Shares Safety, Efficacy, and Pharmacokinetics of Continuous Subcutaneous Lenalidomide in Multiple Myeloma (MM), A Study Evaluating the Safety and Efficacy of Multiple Treatments in Participants With Multiple Myeloma, A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Mul, Phase II Study of QLS32015 Combination Therapy in the Treatment of Multiple Myeloma.
Shares Phase II Study of QLS32015 Combination Therapy in the Treatment of Multiple Myeloma, A Study of Daratumumab, Selinexor and Backbone Treatments of Multiple Myeloma Patients, Cereblon (CRBN).
Shares A Study of Rocbrutinib in Participants With Relapse or Refractory Non-GCB Diffuse Large B-Cell Lymphoma, A Study to Evaluate Glofitamab as a Single Agent vs. Investigator's Choice in Participants With Relapsed/Refractory Mantle Cell Lymphoma, Lupeng Pharmaceuticals, RELEVANCE.
Shares Isatuximab in Combination With Lenalidomide and Dexamethasone in High-risk Smoldering Multiple Myeloma, Study of AZD0120 in Newly Diagnosed Multiple Myeloma Ineligible for ASCT, IMROZ, Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple.
Shares A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma, frontMIND, Safety and Pharmacokinetics Study of a Modified Tafasitamab IV Dosing Regimen Combined With Lenalidomide in R-R DLBCL Patients, Study to Evaluate the Safety and Efficacy of Tafasitamab Plus Lenalidomide in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (.