Daratumumab Plus Carfilzomib, Dexamethasone May Be Effective in Lenalidomide-Refractory Multiple Myeloma

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The increase in use of lenalidomide as maintenance treatment emphasizes the need to explore additional treatment options among patients with lenalidomide-refractory multiple myeloma.
The increase in use of lenalidomide as maintenance treatment emphasizes the need to explore additional treatment options among patients with lenalidomide-refractory multiple myeloma.
The following article features coverage from the American Society of Clinical Oncology (ASCO) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

CHICAGO—Daratumumab plus weekly carfilzomib and dexamethasone was safe and effective among patients with relapsed and refractory multiple myeloma (RRMM) who had previously failed lenalidomide therapy, according to a presentation at the American Society of Clinical Oncology (ASCO) 2018 Annual Meeting on Friday, June 1.

The increase in use of lenalidomide as maintenance treatment emphasizes the need to explore additional treatment options among patients with lenalidomide-refractory MM. Evidence from previous studies have shown that daratumumab-based regimens significantly decrease the risk of progression or death and induce rapid, deep, and durable response in RRMM and newly diagnosed MM.

For a subgroup analysis of the phase 1b MMY1001 study (ClinicalTrials.gov Identifier: NCT01998971), researchers assessed the outcomes of 85 patients with RRMM that were treated with carfilzomib, dexamethasone, and daratumumab either as a standard first dose or split first dose. Eligible patients had previously received 1 to 3 lines of therapy and were carfilzomib-naive.

A total of 51 patients were lenalidomide refractory, refractory was defined as experiencing disease progression 60 days or less after the last line of therapy, and were representative of the overall study population.

Results showed that after a median of 12.0 months of follow-up, the median progression-free survival (PFS) was 14.1 months (95% CI, 9.4-not evaluable [NE]) and the 12-month PFS rate was 62% among lenalidomide-refractory patients. The overall survival (OS) was 21.1 months (95% CI, 18.8-NE) and the 12-month OS rate was 75%.

The overall response rate (ORR) among all patients was 84%, and was 79% among patients who were lenalidomide-refractory. Five percent and 2% of patients overall and those who were lenalidomide-refractory achieved minimal residual disease of 10-5; the median time to MRD negativity of 10-5 was 5.1 months.

Frequently observed hematologic grade 3 to 4 treatment-related adverse effects included thrombocytopenia, anemia, neutropenia, and lymphopenia. Infusion-related reactions (IRR) occurred in 50% and 36% of standard first dose and split first dose patients, respectively, showing that splitting the first dose of daratumumab was feasible and improved patient convenience; none of the IRRs were grade 3 to 4. The median left ventricular ejection fraction remained stable with manageable cardiac toxicities.

The authors concluded “the combination of daratumumab and weekly carfilzomib and dexamethasone was well tolerated and demonstrated promising efficacy in lenalidomide-refractory patients.”

Read more of Cancer Therapy Advisor's coverage of the American Society of Clinical Oncology (ASCO) 2018 meeting by visiting the conference page.

Reference

  1. Chari A, Martinez-Lopez J, Mateos MV, et al. Daratumumab (DARA) in combination with carfilzomib and dexamethasone (D-Kd) in lenalidomide (Len)-refractory patients (pts) with relapsed multiple myeloma (MM): subgroup analysis of MMY1001. Oral presentation at: 2018 ASCO Annual Meeting; June 1-5, 2018; Chicago, IL.

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