Why consider Ixazomib - Ixazomib in the real world
The real-world INSIGHT-MM and RMG studies complement findings from the pivotal Phase 3 TOURMALINE-MM1 trial, with patients demonstrating similar median progression-free survival (PFS) and a favourable safety profile.1–4
Randomised controlled trials (RCTs) are the gold standard for evaluating therapeutic efficacy, but many people with multiple myeloma are excluded due to age, or comorbidities.5-8 Real-world evidence (RWE) complements RCTs by assessing how interventions perform in routine clinical practice among broader, more representative patient populations.5-7 Data from the INSIGHT-RMG study are reported here.1
RWE study synopsis
Hájek R et al, 2021, conducted an expanded, pooled analysis of data for relapsed/refractory multiple myeloma (RRMM) patients who received IRd from the INSIGHT-MM and the Czech RMG studies.1
- INSIGHT-MM is the largest global, prospective, observational study in multiple myeloma (MM) to date, which has enrolled 4311 adult patients with newly diagnosed MM or RRMM who have received 1–3 prior therapies, from 15 countries worldwide, including the UK.1
- The Czech RMG includes clinical data on diagnosis, treatment, treatment outcomes and survival for >7000 patients with MM.1
For this analysis, adult patients with RRMM, with ≥1 prior therapy, who had been treated with Ixazomib in combination with lenalidomide (R) and dexamethasone (d) (IRd), were identified.1
Study design1

Adapted from Hájek R, et al. 2021.1
*Determined as per investigator assessment, using International Myeloma Working Group criteria.1
†Estimated using Kaplan-Meier methodology.1
Patient characteristics by line of therapy1

Adapted from Hájek R, et al. 2021.1
ǂn=216/105/65.
§n=260/115/90.
Effectiveness
At data cut-off, 263 patients from 13 countries who had received IRd had been included in the analyses, with 132 patients from INSIGHT-MM and 131 from the Czech RMG.1
Progression-free survival (PFS) with IRd

Adapted from Hájek R et al, 2021.1
Effectiveness of IRd in a real-world setting (median PFS: 21.2 months) is similar to the efficacy of IRd reported in the TOURMALINE-MM1 trial (median PFS: 20.6 months)1,4
Median PFS was 26.0, 23.8, 13.6 and 6.7 months in patients receiving IRd in 2L, 3L, 4L and >4L, respectively.1
- Median PFS was significantly longer in patients receiving IRd in 2L vs. >2L (HR: 0.66; 95% CI: 0.45–0.95; p = 0.026) and also for patients who received IRd in 2L and 3L versus >3L (HR: 0.44; 95% CI: 0.29–0.66; p < 0.001).1
Overall survival (OS)1

Adapted from Hájek R et al, 2021.1
Median OS for all patients and for those receiving IRd in 2L, 3L and 4L, was not reached; median OS in >4L was 9.8 months.1
Safety and tolerability
Hájek R et al, 2021, demonstrated similar drug discontinuation rates due to adverse events (AEs) between Ixazomib and lenalidomide in patients taking IRd (N=263). Patients who required dose reduction may have also subsequently discontinued treatment.1
Adverse events leading to Ixazomib and lenalidomide dose reductions and discontinuations in patients taking IRd.1

Adapted from Hájek R et al. 20211
Ixazomib and lenalidomide dose reductions were required in 17% (n=44) and 36% (n=95) of patients treated with IRd, respectively. Ixazomib dose reductions were required in 10% (n=27) of patients due to documented AEs, with the most common AEs leading to these events being diarrhoea, neutropenia, thrombocytopenia and neuropathy.1
Adverse Events leading to Ixazomib dose reductions and discontinuations (N=263)

*More than one AE could be assigned to one patient; each AE was counted only once for each patient.
Adapted from Hájek R et al, 2021 (Supplement).3
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.

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1L, first line; 2L, second line; 3L, third line; 4L, fourth line; AE, adverse event; CI, confidence interval; d, dexamethasone; IRd, Ixazomib in combination with lenalidomide and dexamethasone; ITT, intention to treat; MM, multiple myeloma; OS, overall survival; PFS, progression-free survival; R, lenalidomide; RCT, randomised controlled trial; RMG, Registry of Monoclonal Gammopathies; RRMM, relapsed refractory multiple myeloma; RWE, real-world evidence.
1. Hájek R, et al. Future Oncol. 2021;17:2499–2512. 2. Sandecka V, et al. Blood Cancer J. 2023;13:153. 3. Hájek R, et al. Future Oncol. 2021;17(Suppl):2499–2512. 4. Moreau P, et al. N Engl J Med. 2016;374(17):1621–1634. 5. Derman BA, et al. Blood Rev. 2022;53:100913. 6. Terpos E, et al. Blood Cancer J. 7. Chodankar D. Perspect Clin Res. 2021;12:171–174.2021;11:40. 8. Shah JJ, et al. Clin Lymphoma Myeloma Leuk. 2017;17:575–583.
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