Why consider Ixazomib - Ixazomib in the real world

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

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

Study design of the INSIGHT-RMG real-world study. The study included 263 patients from the INSIGHT-MM and RMG studies, with 19% of patients from the UK and representation from 13 countries overall. Eligibility criteria included 1– 3 prior therapies (INSIGHT-MM) or ≥1 prior therapy (from RMG), including an Ixazomib-based regimen. Key study endpoints included progression-free survival (PFS), duration of treatment (DoT), time to next treatment (TTNT), overall survival (OS), and safety.

Patient characteristics by line of therapy1

Table of patient characteristics by line of therapy in the INSIGHT-RMG study. Characteristics shown include sex, median age at initiation of IRd, ISS stage at diagnosis, and median time from diagnosis. Among included patients, 44% received IRd at second line, and 35% received IRd at third line. The median age at initiation of IRd was similar to that reported in the TOURMALINE-MM1 randomised controlled trial.

Progression-free survival (PFS) with IRd

Kaplan-Meier Curve showing progression-free survival (PFS) in the INSIGHT-RMG study.

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

A Kaplan-Meier Curve showing overall survival (OS): for patients treated with IRd in the INSIGHT-RMG study.

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

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

Pie charts showing the proportion of patients requiring dose reduction or discontinuation of Ixazomib or
lenalidomide due to adverse events (AEs) in the INSIGHT-RMG study.

Adverse Events leading to Ixazomib dose reductions and discontinuations (N=263)

Table showing adverse events (AEs) leading to Ixazomib dose reduction and discontinuation in the INSIGHT-RMG study.

Ixazomib FAQs

What is Ixazomib?

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. Ixazomib. Summary of Product Characteristics.

What is the licensed indication for Ixazomib?

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.

Where is Ixazomib reimbursed?

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.

How does Ixazomib work?  

Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome.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. Ixazomib. Summary of Product Characteristics.

What is the recommended Ixazomib dose and how is it administered?

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.

How should the dosing be adjusted in special populations?
  • No dose adjustment of Ixazomib is required for patients over 65 years of age
  • 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
  • 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
  • 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.

What are the most common side effects of IRd?

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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