Real-world effectiveness of IRd in R/R myeloma

Although randomized clinical trials (RCTs) are essential for determining the efficacy and safety of any given regimen, they are limited to using a standardized therapy in a highly selected group of patients.1 This is where real-world studies play an important role in understanding efficacy and safety in the overall population by generating long term data to support the original clinical trial data, and ongoing use of a regimen. 1

The TOURMALINE-MM1 (NCT01564537) study was a global phase III, double-blind, placebo-controlled study evaluating the efficacy and safety of the all-oral regimen of ixazomib, lenalidomide and dexamethasone (IRd) in patients with relapsed/refractory (R/R) multiple myeloma (MM).2 The study determined that with the addition of ixazomib to lenalidomide and dexamethasone, progression-free survival (PFS) was significantly longer compared with placebo (median progression-free survival, 20.6 months vs. 14.7 months; hazard ratio (HR) for disease progression or death in the ixazomib group, 0.74; P=0.01).2

Speaking around the recent COMy 2020 meeting, Xavier Leleu, MD, PhD, from Poitiers University Hospital, Poitiers discusses outcomes in relapsed/refractory multiple myeloma patients treated with IRd in routine clinical practice.

Further real-world data to support the original TOURMALINE-MM1 was published this year in Annals of Hematology. This multi-centric, retrospective, observational study evaluated the efficacy and safety of IRd in 155 patients across Greece, the UK and the Czech Republic. Patients were included who had received ixazomib as part of an early access program. The median age of all patients was 68 years, and 91%, 47%, and 17% had received prior bortezomib, thalidomide, and lenalidomide, respectively (median number of prior therapies was 1; range 1–7). The median duration of exposure to ixazomib was 9.6 months.

The outcomes observed in the real-world study were comparable with the original clinical study. The overall response rate was 74% (vs 78% in the phase III study) and the median PFS was reported as 27.6 months.

A small number of patients in the study (14/155, 9%) discontinued IRd due to adverse events/toxicity in the absence of disease progression, and peripheral neuropathy was reported in 35% of patients (3% grades 3–4).

The authors concluded that the findings from this study ‘support the results of the phase III TOURMALINE-MM1 trial in a broader real-world RRMM population’.

References

  1. Mahajan R. Real-world data: Additional source for making clinical decisions. Int J Appl Basic Med Res. 2015;5(2):82.
  2. Moreau P, Masszi T, Grzasko N, et al. Oral Ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016 Apr 28;374(17):1621-34.
  3. Terpos E, Ramasamy K, Maouche N, et al. Real-world effectiveness and safety of ixazomib-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma. Ann Hematol. 2020 Apr 1. doi: 10.1007/s00277-020-03981-z [online ahead of print].