Isatuximab – Novel Anti CD38 Targeted Therapy Promising for Myeloma
by Dr. C.H. Weaver M.D. 2/2019
In an update from the phase III ICARIA-MM trial presented at the 2019 American Society of Clinical Oncology meeting researchers reported that the combination of the anti-CD38 monoclonal antibody isatuximab with Pomalyst (pomalidomide) and dexamethasone (Pd) extended progression-free survival (PFS) to 11.5 months in patients with relapsed/refractory multiple myeloma (MM) which is nearly five months longer than with Pd alone.(3,4)
Multiple myeloma is the second most common hematologic malignancy, with more than 138,000 individuals diagnosed worldwide each year. Multiple myeloma remains incurable in the vast majority of patients, resulting in significant disease burden. (1,2)
Isatuximab is a precision cancer medicine that targets a specific part of the CD38 antigen expressed on myeloma cells and is capable of triggering multiple, distinct mechanisms of action that are believed to promote programmed tumor cell death (apoptosis). CD38 is highly and uniformly expressed on multiple myeloma cells and is a cell surface receptor target for antibody-based therapeutics in multiple myeloma and other malignancies.
The current study evaluated the benefit of Isatuximab in combination with the standard of care on prolonging progression free survival as compared to standard of care in patients with relapsed/refractory multiple myeloma.
The phase III randomized, open-label, multicenter ICARIA-MM trial included 307 patients with relapsed/refractory MM who had received at least two prior lines of therapy (including lenalidomide and a proteasome inhibitor [PI]). Participants also had disease that was refractory to their last therapy.(3,4)
Patients were treated with either isatuximab plus Pd (n=154) or Pd alone (n=153) until disease progression or unacceptable toxicity and directly compared.
After an average follow-up period of 11.6 months from initiation of treatment the average time to cancer progression was 11.5 months with isatuximab compared with 6.5 months for Pd. The overall survival duration has not yet been reached in either group. Overall 72% of isatuximab treated patients survive one year from treatement compared to 63% for prednisone alone.
Dr. Richardon and colleagues from Dana Farber Cancer Institute concluded that the addition of isatuximab to Pd resulted in significant improvement in overall and depth of response. Responses occurred more rapidly in the isatuximab and nearly twice as many patients in the isatuximab group achieved at least a partial response.
Treatment appeared to be well tolerated, Dr. Richardson and colleagues reported, with patients receiving isatuximab for a median of 41 weeks, compared with 24 weeks in the Pd alone group.Together, these safety and efficacy results suggest that isatuximab plus Pd is “an important new treatment option for the management of relapsed/refractory MM,” Dr. Richardson concluded. However, these results will need to be confirmed in longer-term follow-up, and also compared with other monoclonal antibody–based regimens for MM.
- Kazandjian. Multiple myeloma epidemiology and survival: A unique malignancy. Semin Oncol. 2016;43(6):676-681. doi:10.1053/j/seminoncol.2016.11.00.
- Cowan AJ, Allen C, BaracA, et al. Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016. JAMA Oncol. 2018;4(9):1221–1227. doi:10.1001/jamaoncol.2018.2128
- 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). Abstract #8004. Presented at the 2019 ASCO Annual Meeting, June 2, 2019; Chicago, IL.