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The combination of ixazomib, lenalidomide and dexamethasone for patients with relapsed/refractory multiple myeloma in real-world

The combination of ixazomib, lenalidomide and dexamethasone (IRd) has been recently approved as treatment option of relapsed/refractory multiple myeloma (RRMM) patients who have received 1-3 prior lines of therapy. This study of the Greek myeloma study group evaluated the efficacy and safety of IRd in the real world practice, where data are limited. The data demonstrate that almost all patients with RRMM had a clinical benefit and IRd has an acceptable safety profile.

The study presented during EHA 2017 was a retrospective, non-interventional study, which recorded IRd treatment data from patients with RRMM who participated in the name-patient program of ixazomib in Greece. The primary endpoint was the evaluation of overall response rate (ORR). Secondary endpoints included: treatment duration, time to response, duration of response, percentage of patients who experienced adverse events, needed dose modification or treatment discontinuation.

In the present study 41 patients were included. Of those patients, 35 had received at least 3 cycles of IRd on the date of data analysis and thus they were included in the present report. The median line of previous therapies was one (range: 1-5): 71.4% (25/35) patients had received one prior treatment, while 20.0% (7/35), 5.7% (2/35) and 2.9% (1/35) had received 2, 3 and 5 prior treatment lines, respectively. Overall, 82.9% (29/35) of patients had been exposed to proteasome inhibitors prior to IRd and 48.6% (17/35) to IMiDs. Autologous transplantation had been given in 42.9% (15/35) of patients.

The median treatment duration was 7.1 months among the patients included in the present report. Data for response were available for 34 patients; very good partial response was recorded in 35.3% (12/34), partial response in 32.4% (11/34), minor response in 2.9% (1/34) and stable disease in 26.5% (9/34). The ORR (partial response or better) was 67.6%, 70.8% among those who received IRd in the second line, and 60.0% among those who received IRd beyond the second line. In addition, ORR tended to be higher as the time of exposure to ixazomib increased, with ORR for patients exposed to ixazomib for at least 6, 7 and 8 months of 70.8% (17/24), 76.5% (13/17) and 91.8% (9/11), respectively. Median time to best response was 1.2 months.

Regarding toxicity, treatment interruptions due to adverse events were recorded for 11.4% (4/35) of patients, while 20.0% (7/35) of patients discontinued treatment. 31.4% (11/35) of patients experienced peripheral neuropathy; of those events, 54.5% (6/11) resolved, while 45.4% (5/11) had not resolved (three were grade 1, one grade 2, and one of grade 3) at the end of follow-up. In addition, 31.4% (11/35) of patients developed gastrointestinal adverse events, 11.4% (4/35) experienced pneumonia, 9.4% (3/32) hypertension, 5.7% (2/35) cataract and herpes zoster, and 2.9% (1/35) deep vein thrombosis; no cardiac arrhythmia or other cardiac events were recorded, while osteonecrosis of the jaw developed in 5.7% (2/35) of the patients.

In conclusion, this study showed that the IRd regimen produces an ORR of near 68% and a clinical benefit in almost all patients with RRMM who are treated in real-world practice. Furthermore, IRd acts rapidly and has an acceptable toxicity profile with no cardiac events.


Terpos E, Katodritou E, Kotsopoulou M, et al. “Real World” data on the efficacy and safety of ixazomib in combination with lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: a study of the Greek myeloma study group. EHA 2017, poster presentation, abstract 1249.

1. Treatment line in which IRd was given: ‘taart’ diagram poster
2. Prior treatment exposure: blokkendiagram poster
3. Treatment response: staafdiagram poster
4. Toxicity: blokkendiagram poster


Speaker Evangelos Terpos


Evangelos Terpos, MD, PhD, University of Athens, School of Medicine, Athens, Greece


See: Keyslides


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