Ixazomib versus olverembatinib in chronic myeloid leukemia and multiple myeloma

The REMIX study (NCT03012880) evaluated ixazomib (Ixazomib) in combination with lenalidomide (Revlimid) and dexamethasone (IXA-Rd) in patients with relapsed/refractory multiple myeloma. A total of 376 patients participated in the study. The median age was 71 years, and 18.2% of patients had an ECOG performance status score of 2 or higher. In addition, 48.8% of patients were frail and 62.8% had 1 comorbid disease. Before treatment, 60.4% of patients received first-line treatment, of which 60% received IXA-Rd as second-line treatment, 18% received third-line treatment, and 22% received fourth-line and above treatment. 44.5% of patients underwent autologous stem cell transplantation.

A total of340 patients received the full daily dose of 4 mg of dexamethasone, and 36 patients received a daily dose of 3 mg or less. The starting dose of lenalidomide was 25 mg in 61.3% of patients, 20 mg in 4% of patients, 10 mg in 16.9% of patients, and less than 10 mg in 17.7% of patients. Dexamethasone was administered at 40 mg in 52.7% of patients and 20 mg in 43% of patients. The median follow-up time was 28.7 months, and 226 of 358 patients progressed or died. The progression-free survival (PFS) analysis did not include 1 patient lost to follow-up or 17 patients who were assessed to have progressive disease but were still alive.

Across the entire population, median PFS was 19.1 months (95% CI, 15.9-21.5) and for those who received IXA-Rd as second-line therapy, median PFS was 21.5 months (95% CI, 19.2-24.8). Median PFS was 21.9 months (95% CI, 16.2-28.7) for patients who received IXA-Rd as third-line therapy and 5.8 months (95% CI, 4.8-9.4) for patients who received it as fourth-line therapy or higher (P<0.01).

For patients younger thanmedian PFS was 19.1 months (95% CI, 15.9-21.9), and for patients 80 years or older, median PFS was 17.4 months (95% CI, 10.8-23.0) (P=0.06). Among frail patients, median PFS was 14.6 months (95% CI, 10.8-21.3), compared with 21.5 months (95% CI, 17.0-29.1; P<0.01). If patients had previously received ASCT, the median PFS was 19.8 months (95% CI, 14.3-24.8), whereas for patients who had not received ASCT, the median PFS was 17.8 months (95% CI, 14.4-21.5; p<0.30). The median PFS of those with previous comorbidities was 19.5 months (95% CI, 12.8-24.0), and the median PFS of those without comorbidities was 18.8 months (95% CI, 15.3-21.9; P=0.67).

Investigator-assessedThe objective response rate (ORR) of IXA development was 73.1%. 14.5% of patients experienced complete response (CR), 30.5% of patients experienced very good partial response (VGPR), 28.1% of patients experienced PR, and 10.6% of patients experienced stable disease. For patients under 80 years old, the ORR was 72.4%, and for patients over 80 years old, the ORR was 76.8%. When IXA-Rd was used as second-line or third-line treatment, the ORR increased to 80.3% and 70%, respectively. When given as fourth-line therapy, the ORR dropped to 54.4%. Duration of response was estimated at 10.9 months (95% confidence interval, 8.7-14.8). Median overall survival (OS) had not been reached at the time of analysis.

Dose reductions occurred in 26.4% and 34.4% of patients in the ixazomib and lenalidomide groups, respectively. Treatment discontinuation occurred in 22.1% of patients in the ixazomib group and 21.3% in the lenalidomide group. Treatment discontinuation occurred in 74.1% of ixazomib patients and 57.3% of lenalidomide patients. Adverse reactions (AEs) occurred in 78.2% of patients, serious adverse reactions (SAEs) in 54.3% of patients, and treatment-related adverse reactions (TRAEs) in 40.7% of patients. The most common TRAEs included diarrhea (13.9%), thrombocytopenia (12.6%), and nausea (8.5%). The most common SAEs were thrombocytopenia (12.2%), plasma cell myeloma (9.5%), and death (7.8%).