# Pomalidomide and dexamethasone regimen
The pomalidomide–dexamethasone regimen (Pd) is an all-oral combination treatment for relapsed and refractory multiple myeloma, in which the immunomodulatory drug pomalidomide is taken once daily on days 1–21 of each 28-day cycle with a break on days 22–28, alongside weekly pulsed dexamethasone on days 1, 8, 15, and 22.[22](https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0c16478-1a0c-4be0-be75-cb9e4543d71a) It is licensed for adults whose disease has progressed after at least two prior therapies including lenalidomide and a proteasome inhibitor, and it also serves as the doublet backbone for approved pomalidomide-based triplets.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204026s034lbl.pdf) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/) The pomalidomide–dexamethasone regimen was approved by the FDA and the EMA in 2013.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/)
| Key fact | Detail |
|---|---|
| Indication (US) | Adults with multiple myeloma after at least two prior therapies including lenalidomide and a proteasome inhibitor, with progression on or within 60 days of the last therapy[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204026s034lbl.pdf) |
| Standard dosing | Pomalidomide 4 mg orally once daily on days 1–21 of 28-day cycles; dexamethasone 40 mg on days 1, 8, 15, 22 (20 mg if over 75 years)[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204026s034lbl.pdf) • [3](https://clinicaltrials.gov/study/NCT01311687) |
| Mechanism | Pomalidomide binds cereblon in a CUL4-Roc1 E3 ubiquitin ligase complex, driving degradation of Ikaros (IKZF1) and Aiolos (IKZF3) and downregulation of IRF4 and MYC[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5574598/) • [5](https://www.ema.europa.eu/en/documents/product-information/imnovid-epar-product-information_en.pdf) |
| Pivotal efficacy | MM-003: median progression-free survival 4.0 vs 1.9 months versus high-dose dexamethasone (HR 0.48); overall response rate 31% vs 10%[6](https://doi.org/10.1016/s1470-2045%2813%2970380-2) |
| Dominant toxicities | Grade 3/4 neutropenia 48–56%, grade 3/4 infections about 30–34%; thromboprophylaxis is mandatory[6](https://doi.org/10.1016/s1470-2045%2813%2970380-2) • [7](https://onlinelibrary.wiley.com/doi/10.1111/ejh.12903) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/) |
| Current position | Still a licensed doublet, but newer triplets, belantamab-based regimens, and T-cell redirecting therapies now take priority in many relapse settings[8](https://www.nature.com/articles/s41571-025-01041-x) |
## How it works
Pomalidomide is an immunomodulatory imide drug whose cellular activities are mediated through cereblon (CRBN), its direct molecular target. CRBN is a substrate-recognition component of a cullin ring E3 ubiquitin ligase complex that also contains DDB1, CUL4, and Roc1. When pomalidomide binds CRBN, the complex recruits the transcription factors Ikaros (IKZF1) and Aiolos ([IKZF3](https://www.edgepedia.org/ikzf3)) as neosubstrates; they are ubiquitinated and degraded within hours of treatment, and the transcription factors IRF4 and MYC are negatively regulated within 48 hours.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5574598/) • [5](https://www.ema.europa.eu/en/documents/product-information/imnovid-epar-product-information_en.pdf) This produces direct cytotoxic effects on myeloma cells and broader immunomodulatory effects, including increased T-lymphocyte and NK-cell proliferation and altered cytokine production.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5574598/)
Dexamethasone contributes as a corticosteroid with independent anti-myeloma activity; in trials the combination was consistently more active than either pomalidomide alone or dexamethasone alone.[6](https://doi.org/10.1016/s1470-2045%2813%2970380-2) • [9](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204026Orig1s000CrossR.pdf)
## How it is done
The recommended schedule is pomalidomide 4 mg once daily on days 1 through 21 of repeated 28-day cycles, continued until disease progression, with dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204026s034lbl.pdf) • [5](https://www.ema.europa.eu/en/documents/product-information/imnovid-epar-product-information_en.pdf) Patients over 75 years start dexamethasone at 20 mg on the same days.[3](https://clinicaltrials.gov/study/NCT01311687) • [5](https://www.ema.europa.eu/en/documents/product-information/imnovid-epar-product-information_en.pdf) The 4 mg dose on the 21-of-28-day schedule is the maximum tolerated dose established in the phase I portion of study CC-4047-MM-002.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5574598/)
Dose adjustments apply to organ impairment. Patients with severe renal impairment requiring dialysis take 3 mg daily, after hemodialysis on dialysis days; no dose adjustment is otherwise required for renal impairment, because [population pharmacokinetic modeling](https://www.edgepedia.org/population-pharmacokinetic-modeling) showed that moderate to severe renal dysfunction does not affect pomalidomide clearance.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204026s034lbl.pdf) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/) • [5](https://www.ema.europa.eu/en/documents/product-information/imnovid-epar-product-information_en.pdf) For hepatic impairment, the dose is 3 mg in Child-Pugh A or B and 2 mg in Child-Pugh C; hepatic impairment raised pomalidomide exposure (AUC) by 51%, 58%, and 72% in Child-Pugh A, B, and C respectively.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204026s034lbl.pdf) • [10](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dee932c5-0c7c-45f0-b2bb-c027badee537)
Supportive care centers on mandatory thromboprophylaxis and vigilance for cytopenias and infection. In a pooled analysis of 1088 patients, pomalidomide interruptions were recorded in 66.0% and dose reductions in 24.2% of patients.[7](https://onlinelibrary.wiley.com/doi/10.1111/ejh.12903)
## Origin
Pomalidomide was developed under the code CC-4047. Celgene submitted the New Drug Application on April 10, 2012, based on the phase 1/2 study CC-4047-MM-002 (221 patients) and the phase 2 IFM 2009-02 study (84 patients).[9](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204026Orig1s000CrossR.pdf) The FDA approved pomalidomide on February 8, 2013, for relapsed/refractory myeloma after at least two prior therapies including lenalidomide and bortezomib, and the EMA followed in 2013.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5574598/) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/)
An early phase II study of 60 patients with no more than three prior lines of therapy used 2 mg pomalidomide daily plus 40 mg weekly dexamethasone and reported an overall response rate of 65% with a median duration of response of 21.3 months.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5574598/) The pivotal randomized evidence came from the NIMBUS trial (MM-003, NCT01311687), a Celgene-sponsored phase 3 study started March 11, 2011, that enrolled 455 patients and was reported by Jesus San Miguel, Katja Weisel, Philippe Moreau, and colleagues in The Lancet Oncology in 2013.[6](https://doi.org/10.1016/s1470-2045%2813%2970380-2) • [3](https://clinicaltrials.gov/study/NCT01311687) In MM-003, 302 patients received pomalidomide plus low-dose dexamethasone and 153 received high-dose dexamethasone; median progression-free survival was 4.0 months versus 1.9 months (hazard ratio 0.48), and the overall response rate was 31% versus 10%.[6](https://doi.org/10.1016/s1470-2045%2813%2970380-2) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/) The trial registry records updated median overall survival of 16.0 months versus 8.1 months (HR 0.49; \( p < 0.001 \)).[3](https://clinicaltrials.gov/study/NCT01311687) NICE's appraisal, accounting for the 56% of control-arm patients who crossed over, put the median overall survival gain between 4.6 and 7.0 months depending on the adjustment method.[11](https://www.nice.org.uk/guidance/ta427/chapter/4-Committee-discussion) In MM-003, benefit was retained independent of age over 75 years and of high-risk cytogenetics (17p deletion, t(4;14)).[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/)
## Variants
Pd is the backbone for several approved and investigational triplets:
- **Pomalidomide–bortezomib–dexamethasone (PVd)**: in OPTIMISMM (559 patients), reported by [Paul G. Richardson](https://www.edgepedia.org/paul-g-richardson) and colleagues in The Lancet Oncology in 2019, median progression-free survival was 11.2 versus 7.1 months versus bortezomib–dexamethasone (HR 0.61), with an overall response rate of 82.2% versus 50%.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/) • [12](https://doi.org/10.1016/s1470-2045%2819%2930152-4)
- **Daratumumab–Pd (DPd)**: in APOLLO, reported by [Meletios A. Dimopoulos](https://www.edgepedia.org/meletios-dimopoulos) and colleagues in The Lancet Oncology in 2021, adding subcutaneous daratumumab gave median progression-free survival of 12.4 versus 6.9 months (HR 0.63) and overall response 69% versus 46%, supporting 2021 approvals.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/) • [13](https://doi.org/10.1016/s1470-2045%2821%2900128-5)
- **Isatuximab–Pd (Isa-Pd)**: in ICARIA-MM (307 patients randomized), median progression-free survival was 11.5 versus 6.5 months (HR 0.596; \( p = 0.001 \)); the final overall survival analysis showed 24.6 versus 17.7 months (HR 0.78), a 6.9-month improvement.[14](https://pubmed.ncbi.nlm.nih.gov/31735560/) • [15](https://haematologica.org/article/view/11432)
- **Belantamab mafodotin plus Pd (BelaPd)**: in DREAMM-8, reported by Meletios A. Dimopoulos, Meral Beksac, Ludek Pour, and colleagues in the New England Journal of Medicine in 2024, Bel-Pom-Dex improved progression-free survival over pomalidomide–bortezomib–dexamethasone (HR 0.52; at the October 2024 data cut, median 32.6 versus 12.5 months).[16](https://doi.org/10.1056/nejmoa2403407) • [17](https://www.ncbi.nlm.nih.gov/books/NBK621334/)
- **Carfilzomib–Pd (KPd)**: in the phase 2 SELECT trial at first or second relapse, median progression-free survival was 11.1 months and median overall survival 18.8 months, but KPd is not approved by the EMA or FDA for relapsed/refractory myeloma.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/)
## Applications
In the United States, POMALYST with dexamethasone is indicated for adults who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have progressed on or within 60 days of completing the last therapy.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204026s034lbl.pdf) In the European Union, Imnovid carries two indications: with dexamethasone after two prior regimens including lenalidomide and bortezomib, and with bortezomib and dexamethasone after at least one prior regimen including lenalidomide, using 4 mg on days 1–14 of 21-day cycles in the triplet.[5](https://www.ema.europa.eu/en/documents/product-information/imnovid-epar-product-information_en.pdf) In England, NICE recommends pomalidomide with low-dose dexamethasone only at third or subsequent relapse, after at least three previous treatments including lenalidomide and bortezomib, and only with the discount agreed in the patient access scheme.[11](https://www.nice.org.uk/guidance/ta427/chapter/4-Committee-discussion)
## Limitations and alternatives
The doublet's main limitations are depth and durability of response and hematologic toxicity. In a pooled analysis of 1088 patients from MM-002, MM-003, and MM-010, the most common grade 3/4 adverse events were neutropenia (56.2%), anemia (32.3%), and thrombocytopenia (25.8%); grade 3/4 infections occurred in 33.7%.[7](https://onlinelibrary.wiley.com/doi/10.1111/ejh.12903) In MM-003, grade 3–4 neutropenia occurred in 48% versus 16% with high-dose dexamethasone, and grade 3–4 pneumonia in 13% versus 8%.[6](https://doi.org/10.1016/s1470-2045%2813%2970380-2) Only 4% of Pd patients discontinued for treatment-related adverse events in MM-003.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC5574598/)
Thrombosis risk is managed proactively. In the MM-003 trial with mandated anticoagulation, thromboembolic events occurred in 8.0% of Pd patients (venous 4.7%, arterial 3.0%) versus 3.3% with high-dose dexamethasone; with systematic thromboprophylaxis the venous thromboembolism rate is below 5%.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204026s034lbl.pdf) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/) NCCN guidance recommends aspirin for patients with none or one venous thromboembolism risk factor and prophylactic direct oral anticoagulants, low molecular weight heparin, or vitamin-K antagonists for those with more than one risk factor receiving immunomodulatory drugs.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/) Adding pembrolizumab to a thalidomide analog plus dexamethasone increased mortality in two randomized trials and is not recommended outside controlled trials.[1](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204026s034lbl.pdf)
Comparisons with lenalidomide-based and bortezomib-based regimens rest on cross-trial data and on trials such as OPTIMISMM, which randomized PVd against bortezomib–dexamethasone.[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/)
The regimen's position has shifted substantially since 2023. The 2025 EHA–EMN guidelines note that 14 novel regimens have been approved by the EMA and/or FDA since the 2021 guidelines, and that for patients refractory to both lenalidomide and daratumumab, belantamab mafodotin plus pomalidomide–dexamethasone and ciltacabtagene autoleucel are the preferred options in the relapse setting.[8](https://www.nature.com/articles/s41571-025-01041-x) In DREAMM-7, reported by Vania Hungria, Pawel Robak, Marek Hus, and colleagues in the New England Journal of Medicine in 2024, belantamab mafodotin with bortezomib–dexamethasone gave a progression-free survival hazard ratio of 0.41 versus daratumumab–bortezomib–dexamethasone, with 36-month overall survival of 74% versus 60%.[18](https://doi.org/10.1056/nejmoa2405090) • [8](https://www.nature.com/articles/s41571-025-01041-x) In MonumenTAL-3, reported by Roberto Mina, Meral Beksac, Paula Rodríguez-Otero, and colleagues in the New England Journal of Medicine in 2026, talquetamab combined with daratumumab or with daratumumab–pomalidomide conferred significantly longer progression-free survival than daratumumab–pomalidomide–dexamethasone.[19](https://doi.org/10.1056/nejmoa2604657) • [20](https://www.nature.com/articles/s41571-026-01191-6) At the front line, the 2026 ASCO–[Ontario Health](https://www.edgepedia.org/ontario-health) living guideline recommends quadruplet therapy with daratumumab or isatuximab plus bortezomib, lenalidomide, and dexamethasone as initial therapy for transplant-eligible and suitable transplant-ineligible patients, and triplet therapy or T-cell redirecting therapies for relapsed or refractory disease.[21](http://www.ingentaconnect.com/content/wk/jco/2026/00000044/00000010/art00011) Pd remains a licensed, orally administered option for heavily pretreated patients, but it increasingly competes with these higher-efficacy alternatives in the relapse pathway.
## References
1. [POMALYST (pomalidomide) prescribing information, revised 2/2025](https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/204026s034lbl.pdf)
2. [Pomalidomide- and dexamethasone-based regimens in the treatment of refractory/relapsed multiple myeloma (review)](https://pmc.ncbi.nlm.nih.gov/articles/PMC9109494/)
3. [ClinicalTrials.gov NCT01311687 (NIMBUS / MM-003) trial record](https://clinicaltrials.gov/study/NCT01311687)
4. [Pomalidomide in the treatment of multiple myeloma: design, development and place in therapy](https://pmc.ncbi.nlm.nih.gov/articles/PMC5574598/)
5. [Imnovid (INN-pomalidomide) EMA product information](https://www.ema.europa.eu/en/documents/product-information/imnovid-epar-product-information_en.pdf)
6. [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 (The Lancet Oncology, 2013)](https://doi.org/10.1016/s1470-2045%2813%2970380-2)
7. [Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low-dose dexamethasone: A pooled analysis](https://onlinelibrary.wiley.com/doi/10.1111/ejh.12903)
8. [EHA–EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma](https://www.nature.com/articles/s41571-025-01041-x)
9. [FDA NDA cross-discipline review (204026Orig1s000) for pomalidomide](https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204026Orig1s000CrossR.pdf)
10. [DailyMed - POMALIDOMIDE capsule (official label)](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dee932c5-0c7c-45f0-b2bb-c027badee537)
11. [NICE TA427 committee discussion: Pomalidomide for multiple myeloma previously treated with lenalidomide and bortezomib](https://www.nice.org.uk/guidance/ta427/chapter/4-Committee-discussion)
12. [Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial (The Lancet Oncology, 2019)](https://doi.org/10.1016/s1470-2045%2819%2930152-4)
13. [Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial (The Lancet Oncology, 2021)](https://doi.org/10.1016/s1470-2045%2821%2900128-5)
14. [Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study](https://pubmed.ncbi.nlm.nih.gov/31735560/)
15. [Isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone: final overall survival analysis (Haematologica)](https://haematologica.org/article/view/11432)
16. [Meletios Athanasios Dimopoulos and colleagues (2024). Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma. New England Journal of Medicine.](https://doi.org/10.1056/nejmoa2403407)
17. [Belantamab mafodotin with pomalidomide and dexamethasone for previously treated multiple myeloma (NICE evaluation, NCBI Bookshelf)](https://www.ncbi.nlm.nih.gov/books/NBK621334/)
18. [Vania Hungria and colleagues (2024). Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma. New England Journal of Medicine.](https://doi.org/10.1056/nejmoa2405090)
19. [Roberto Mina and colleagues (2026). Talquetamab–Daratumumab in Relapsed or Refractory Myeloma. New England Journal of Medicine.](https://doi.org/10.1056/nejmoa2604657)
20. [More options, more questions in the management of early relapsed and/or refractory multiple myeloma (Nature Reviews Clinical Oncology, 31 July 2026)](https://www.nature.com/articles/s41571-026-01191-6)
21. [Treatment of Multiple Myeloma: ASCO–Ontario Health (Cancer Care Ontario) Living Guideline](http://www.ingentaconnect.com/content/wk/jco/2026/00000044/00000010/art00011)
22. [DailyMed - POMALIDOMIDE capsule](https://www.dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0c16478-1a0c-4be0-be75-cb9e4543d71a)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Medicines and therapeutics › Cancer chemotherapy and regimens › Multiple myeloma and hematologic regimens*
*Initially written Sep 29, 2026 · Edited: Oct 15, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license