Why consider Ixazomib - Randomised controlled trial data
Ixazomib is the first and only oral proteasome inhibitor that can help your patients if their multiple myeloma comes back.1
There is a wealth of evidence, including both randomised controlled trial (RCT) data and real-world evidence (RWE), demonstrating that Ixazomib in combination with lenalidomide (R) and dexamethasone (d) (IRd) is associated with improved progression-free survival (PFS) vs placebo + Rd, and a favourable safety profile.1–3
Why consider Ixazomib - RCT Evidence
TOURMALINE-MM1, the pivotal study demonstrating the benefit of Ixazomib in patients with relapsed/refractory multiple myeloma (RRMM) was an international, randomised, double-blind, placebo-controlled, multicentre Phase 3 clinical trial in 722 patients.2,3 This study demonstrated the efficacy and safety of IRd.1-3
Study design3
In the phase 3 TOURMALINE-MM1 trial, 722 patients with RRMM (including patients from the UK) were randomised 1:1 to receive IRd (n=360) or placebo + Rd (n=362).3,4

*Treatment with IRd for longer than 24 cycles should be based on an individual benefit-risk assessment.
Endpoints:
- Primary endpoint: PFS, according to 2011 IMWG criteria, was assessed every 4 weeks until disease progression by a blinded IRC and was based on central laboratory results2
- Key secondary endpoint: Overall survival (OS)1,3
Efficacy
Primary endpoint: PFS1-3
In the TOURMALINE-MM1 study, adding oral Ixazomib to Rd extended PFS in patients with RRMM.1-3

Adapted from Ixazomib SmPC1
- At the time of data cutoff for the first analysis, the median follow-up was 14.8 months in the Ixazomib group and 14.6 months in the placebo group.3
- As assessed by an independent review committee, 129 events of disease progression or death occurred in the Ixazomib group and 157 in the placebo group.3
- The median PFS was found to be 20.6 months in the Ixazomib group and 14.7 months in the placebo group and the hazard ratio for disease progression or death was 0.74 (95% CI, 0.59 to 0.94; P=0.01).1,3
- This represented a 40% longer progression-free survival with IRd as compared with placebo-Rd.3
Median PFS in patients with 2 or 3 prior lines of therapy5

Figure adapted from Takeda Data on File.5
- A second, non-inferential analysis showed that among patients who had received two or three prior lines of therapy, median PFS was 22 months vs 13 months (HR 0.62) for the IRd group vs placebo + Rd group; median follow-up of 23 months1
The benefit of IRd vs Placebo-Rd with respect to PFS was observed across a broad group of patients including:1,3
- High-risk cytogenetics
- 2 to 3 prior lines
- Prior PI exposure
As multiple myeloma is a heterogeneous disease, benefit may vary across subgroups1
Forest plot of PFS in prespecified subgroups1

*Defined as patients with del(17p), t(4;14), or t(14;16).3
This study was not powered to show significance in PFS across these prespecified subgroups.1,3
Adapted from Ixazomib SmPC.1
Secondary endpoint: OS1
- At the final analysis for OS at a median duration of follow up of ~85 months, median OS in the ITT population was 53.6 months for patients in the Ixazomib group and 51.6 months for patients in the placebo group (HR=0.94 [95% CI: 0.78, 1.13; p = 0.495])
- For patients with one prior therapy, the median OS was 54.3 months in the Ixazomib group and 58.3 months in the placebo group (HR = 1.02 [92% CI: 0.80, 1.29])
- For patients with 2 or 3 prior therapies, the median OS was 53.0 months in the Ixazomib group and 43.0 months in the placebo group (HR = 0.85 [95% CI: 0.64, 1.11])
Safety and tolerability
Oral IRd is generally well-tolerated with manageable side effects.1
Adverse reactions occurring in patients treated with IRd: pooled safety data from the TOURMALINE-MM1 and China Continuation studies.1
ADVERSE EVENTS (GRADE: ALL, 3, 4)

Adapted from Ixazomib SmPC1
*Represents a pooling of preferred terms.1
†Reported outside of the Phase 3 studies.1
Ixazomib FAQs
Ixazomib is an oral, highly selective and reversible proteasome inhibitor. Each capsule of Ixazomib contains Ixazomib citrate, a prodrug that rapidly hydrolyses under physiological conditions to its biologically active form, Ixazomib.1
1. Ixazomib. Summary of Product Characteristics.
Ixazomib in combination with lenalidomide and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.1
1. Ixazomib. Summary of Product Characteristics.
In England, IRd is recommended by NICE as an option for treating multiple myeloma in adults if they have already had two or three previous lines of therapy and the company provides Ixazomib according to the commercial arrangement.1 Ixazomib is also available to appropriate patients in Wales and Northern Ireland.2
1. NICE. Ixazomib with lenalidomide and dexamethasone for treating relapsed or refractory multiple myeloma. Available from www.nice.org.uk/guidance/TA870. Accessed March 2026
2. All Wales Therapeutics and Toxicology Centre. Ixazomib citrate. Available at: https://awttc.nhs.wales/accessing-medicines/medicine-recommendations/Ixazomib-citrate-ninlaro.
Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.1 Ixazomib induced apoptosis of several tumour cell types in vitro. Ixazomib demonstrated in vitro cytotoxicity against myeloma cells from patients who had relapsed after multiple prior therapies, including bortezomib, lenalidomide, and dexamethasone.1 The combination of Ixazomib and lenalidomide demonstrated synergistic cytotoxic effects in multiple myeloma cell lines. In vivo, Ixazomib demonstrated antitumour activity in various tumour xenograft models, including models of multiple myeloma. In vitro, Ixazomib affected cell types found in the bone marrow microenvironment including vascular endothelial cells, osteoclasts and osteoblasts.1
1. Ixazomib. Summary of Product Characteristics.
Ixazomib should be taken in combination with lenalidomide and dexamethasone.1
- The recommended starting dose of Ixazomib is 4 mg administered orally on Days 1, 8, and 15 of a 28-day treatment cycle. Ixazomib should be swallowed whole with water at least 1 hour before or at least 2 hours after food
- The recommended starting dose of lenalidomide is 25 mg administered daily on Days 1 to 21 of a 28-day treatment cycle
- The recommended starting dose of dexamethasone is 40 mg administered on Days 1, 8, 15, and 22 of a 28-day treatment cycle
Prior to initiating a new cycle of therapy:1
- Absolute neutrophil count should be ≥1000/mm3
- Platelet count should be ≥75000/mm3
- Non‑haematologic toxicities should, at the physician’s discretion, generally be recovered to patient’s baseline condition or ≤Grade 1
Antiviral prophylaxis should be considered in patients being treated with Ixazomib to decrease the risk of herpes zoster reactivation. Patients included in studies with Ixazomib who received antiviral prophylaxis had a lower incidence of herpes zoster infection compared to patients who did not receive prophylaxis.1
Thromboprophylaxis is recommended in patients being treated with Ixazomib in combination with lenalidomide and dexamethasone, and should be based on an assessment of the patient's underlying risks and clinical status.1
Ixazomib should be taken at approximately the same time on Days 1, 8, and 15 of each treatment cycle at least 1 hour before or at least 2 hours after food.1 The capsule should be swallowed whole with water. It should not be crushed, chewed, or opened.1
Treatment should be continued until disease progression or unacceptable toxicity.1 Treatment with Ixazomib in combination with lenalidomide and dexamethasone for longer than 24 cycles should be based on an individual benefit risk assessment, as the data on the tolerability and toxicity beyond 24 cycles are limited.1
Refer to the Ixazomib SmPC for full dosing guidelines.
1. Ixazomib. Summary of Product Characteristics.
Elderly1
- No dose adjustment of Ixazomib is required for patients over 65 years of age
Hepatic impairment1
- No dose adjustment of Ixazomib is required for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or total bilirubin > 1-1.5 x ULN and any AST). The reduced dose of 3 mg is recommended in patients with moderate (total bilirubin > 1.5-3 x ULN) or severe (total bilirubin > 3 x ULN) hepatic impairment
Renal impairment1
- No dose adjustment of Ixazomib is required for patients with mild or moderate renal impairment (creatinine clearance ≥ 30 mL/min). The reduced dose of 3 mg is recommended in patients with severe renal impairment (creatinine clearance < 30 mL/min) or end-stage renal disease (ESRD) requiring dialysis. Ixazomib is not dialyzable and, therefore, can be administered without regard to the timing of dialysis
Paediatric population1
- The safety and efficacy of Ixazomib in children below 18 years of age have not been established. No data are available
Refer to the Ixazomib SmPC for the full dose modification guidelines. Refer to the Ixazomib SmPC for an overview of all Ixazomib side effects. For additional information regarding lenalidomide or dexamethasone, please refer to each respective SmPC.
1. Ixazomib. Summary of Product Characteristics.
Clinical studies have shown the most frequently reported adverse reactions (≥ 20%) in 418 patients treated with IRd to be diarrhoea (47%), thrombocytopenia (41%), neutropenia (37%), constipation (31%), upper respiratory tract infection (28%), peripheral neuropathy (28%), nausea (28%), back pain (25%), rash (25%), peripheral oedema (24%), vomiting (23%) and bronchitis (20%). Serious adverse reactions reported in ≥ 2% of patients included diarrhoea (3%), thrombocytopenia (2%) and bronchitis (2%).1
Please refer to the SmPC for further information on the Ixazomib tolerability profile.
1. Ixazomib. Summary of Product Characteristics.

Request a meeting
If you have any questions or would like more information about Ixazomib, click below to request a meeting with one of our Takeda representatives.
CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group Performance Status; HR, hazard ratio; IMWG, International Myeloma Working Group; IRC, independent review committee; IRd, Ixazomib in combination with lenalidomide and dexamethasone; ITT, intention to treat; OS, overall survival; PFS, progression-free survival; PI, proteasome inhibitor; R, lenalidomide; Rd, lenalidomide and dexamethasone; RCT, randomised controlled trial; RWE, real-world evidence.
1. Ixazomib. Summary of Product Characteristics. 2. Mateos MV, et al. Haematologica. 2017;102:1767–1775. 3. Moreau P, et al. N Engl J Med. 2016;374:1621–1634. 4. Moreau P, et al. N Engl J Med. 2016;374(Suppl):1621–1634. 5. Takeda Data on File. EXA/GB/IXA/0004.
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