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Ixazomib, lenalidomide and dexamethasone for relapsed and refractory multiple myeloma – data from the Czech Registry of Monoclonal Gammopathies

In a ‘real world’ setting, the combination of ixazomib, lenalidomide and dexamethasone (IRD) was found to be effective, safe, and well tolerated, even in the elderly population. Results of an analysis of pre-treated patients with relapsed and refractory multiple myeloma from the Czech Republic and Slovakia, presented during EHA 2018, showed that the IRD regimen leads to a significant prolongation of both the progression-free (PFS) and overall survival (OS).

The study at hand included data of patients with RRMM, who started IRD treatment between January 2016 and November 2017 within the context of a compassionate Named Patient Program. The data were required from the Czech Registry of Monoclonal Gammopathies and comprised 118 patients treated in 8 hematological centres from the Czech Republic and Slovakia. The median age was 66.5 years with a male/female ratio of 1.2:1, and standard representation of individual M-protein isotypes and ISS stage. Altogether, 15.3% of the patients had extramedullary disease, and 5.9% had elevated creatinine levels above 176 µmol/L. High-risk cytogenetics, including t(4;14), t(14;16) and del17 were found in 13 patients, precluding a valid statistical analysis of this subgroup of patients. The majority of patients received IRD for their first relapse (58.5%), while 23.7% and 7.6% received it in the context of a second and third relapse, respectively. A small group of patients was treated with IRD in their fourth (5.9%), or further relapse (4.2%). Most patients received prior bortezomib (94.1%), while 40.7% was previously treated with  thalidomide. A minority of patients was pre-treated with lenalidomide (16.9%) or carfilzomib (5.9%). Seventy-four patients (62.7%) underwent previous autologous stem cell transplantation.

The therapeutic response was assessed according to IMWG criteria in 76 patients evaluable at the time of data collection. After a median follow-up of 9.7 months, a complete response (CR) was seen in 11.8% of the patients, with 15.8% having a very good partial response (VGPR). In addition to this, 40.8% of patients obtained a partial response (PR) with the treatment and a minimal response (MR) was seen in 9.2%. Disease stabilization was noted in 14.5% of patients and 7.9% had progressive disease (PD). These response data correspond to a an overall response rate (PR or better) of 68.4% and clinical benefit rate (MR or better) of 77.6%. The median time to response was 1.6 months.

The median OS was not reached, with 12- and 24-months OS rates of 77.4% and 68.8%, respectively. The median  PFS was 23.1 months, with 12-month PFS 60.3% and 24-month PFS 42.0%. Patients treated in their first relapse had significantly better PFS (median not reached) than patients in their second (23.1 months), third (8.7 months) or higher relapse (4.6 months). Patients with extramedullary plasmocytoma (n=18) were found to have a  worse PFS (median 9.0 months) than the rest of the cohort. Most of the toxicities were grade ≤2. The most common grade ≥3 adverse events were neutropenia (37.7%), thrombocytopenia (24.5%), infection (18.9%) and anemia (13.2%). The incidence of other toxicities, such as fatigue, neuropathy, exanthema, diarrhoea and venous thromboembolism were all under 5%.

The investigators concluded that the fully oral IRD regimen belongs to the most effective novel drug combinations in RRMM. The regimen confirmed its efficacy in the ‘real world’ setting. The treatment was safe and well tolerated, even in elderly population. The IRD regimen leads to a PFS prolongation of nearly 2 years and a significant OS improvement. Interestingly, patients who received the regimen early in their disease course (i.e. in the first or second relapse) had significantly better outcomes than patients with more advanced disease. Unfortunately, the IRD regimen does not overcome the adverse impact of extramedullary disease.



Minarik J, Hajek R, Jungova A, et al. Ixazomib, lenalidomide and dexamethasone for relapsed and refractory multiple myeloma – data from the Czech Registry of Monoclonal Gammopathies. Presented during EHA 2018; Abstract PF593.

Spreker Jiri Minarik


Jiri Minarik, MD, PhD, University Hospital Olomouc, Olomouc, Czech Republic


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