|The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
The phase 3 ICARIA-MM trial (ClinicalTrials.gov Identifier: NCT02990338) met its primary end point of improvement in progression-free survival (PFS) for patients with relapsed/refractory multiple myeloma receiving isatuximab in addition to a regimen of pomalidomide and low-dose dexamethasone (Pd) versus Pd alone. The findings of this study were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.1
Isatuximab is an investigational monoclonal antibody that targets a specific epitope on CD38, a glycoprotein expressed on the surface of different types of cells, including malignant plasma cells in multiple myeloma and many types of immune cells. Some evidence suggests that isatuximab-related induction of antibody-dependent cell-mediated toxicity may be an important mechanism of action of this agent in the setting of multiple myeloma.2
This multicenter, open-label, randomized trial enrolled 307 adult patients with multiple myeloma who had received 2 or more prior therapies, including lenalidomide and a proteasome inhibitor, were refractory to the last therapy prior to study entry, and were pomalidomide-naive. Patients were randomly assigned in a 1:1 ratio to receive Pd with or without isatuximab, with the latter agent administered intravenously at a dose 10 mg/kg weekly on days 1, 8, 15, and 22 of the first 28-day cycle, and then on days 1 and 15 of subsequent cycles.
The median age of patients enrolled in the study was 67 years (range, 36-86 years), over 90% and approximately 75% had disease refractory to lenalidomide and a proteasome inhibitor, respectively, and approximately one-fifth had disease characterized by high-risk cytogenetics. The median number of prior therapies was 3.
“This represents a large real-world analysis,” commented Paul G. Richardson, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, who was also the presenter of the study.
At a median follow-up of 11.6 months, median PFS was 11.53 months and 6.47 months for patients receiving treatment with and without isatuximab, respectively (hazard ratio [HR], 0.596; 95% CI, 0.436-0.814; P =.001). Importantly, improvement in PFS with isatuximab was observed across all cytogenetic risk groups, and in patients refractory to lenalidomide.
The benefit of isatuximab was also observed across the secondary end point of overall response rate with 60.4% and 35.3% (P =.0001) of patients treated with or without isatuximab achieving a partial or complete response.
Other efficacy results included rates of very good partial response or better of 31.8% and 8.5% and minimal disease negativity (10-5 sensitivity) of 5.2% and 0% in patients receiving isatuximab or not, respectively. In addition, the median time to next treatment was 9.1 months and not yet reached for those receiving Pd alone or Pd plus isatuximab, and patients receiving the isatuximab regimen had a higher rate of improvement in renal function compared with those receiving Pd. Overall survival was immature at the time of study analysis.
Regarding safety, rates of adverse event-related therapy discontinuation were 7.2% and 12.8% in those treated with isatuximab with and without isatuximab. Nearly 40% of patients receiving isatuximab experienced an infusion reaction.
For patients receiving isatuximab-containing treatment vs not, rates of grade 3 or higher adverse events were reported to be 86.8% and 70.5%, respectively. Of these grade 3 or higher adverse events, 84.8% [with isatuximab] and 70.1% experienced neutropenia, with grade 4 neutropenia more common in patients receiving isatuximab.
Importantly, quality-of-life assessments performed over time did not show significant differences between the 2 study arms.
Dr Richardson concluded his talk by noting that “the combination of isatuximab with Pd is an important new treatment option for our patients with relapsed/refractory melanoma.”
Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.
- Richardson PG, Attal M, Rajkumar SV, et al. A phase III randomized, open label, multicenter study comparing isatuximab, pomalidomide, and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 8004.
- Moreno L, Zabaleta A, Alignani D, et al. Critical analysis on the mechanism of action (MoA) of the anti-CD38 monoclonal antibody isatuximab in multiple myeloma (MM). Blood. 2016;128(22):2105.