Isatuximab Shows Tolerability in Real-World Population With RRMM

Thomas Martin, MD

Regimens containing isatuximab (Sarclisa) demonstrated real-world tolerability in patients with relapsed/refractory multiple myeloma (RRMM), according to first interim results of a study presented at the 2022 International Myeloma Society Annual Meeting.¹

Patient baseline characteristics in the observational IONA-MM study (NCT04458831) were consistent with the trials that led to the approvals of Isa-Pd (isatuximab, pomalidomide [Pomalyst], dexamethasone) or Isa-Kd (isatuximab, carfilzomib [Kyprolis], dexamethasone). Investigators reported an expected level of toxicity in IONA-MM, supporting the use of these regimens outside of clinical trials.

“Currently, there is limited real-world evidence available for patients treated with Isa-Pd or Isa-Kd,” Thomas Martin, MD, clinical professor of medicine, associate chief of hematology, and codirector of the myeloma program at UCSF Medical Center.1

The anti-CD38 monoclonal antibody isatuximab was approved for use in the Isa-PD regimen based on positive outcomes from the phase 3 ICARIA-MM (NCT02990338), and in the Isa-Kd regimen based on the phase 3 IKEMA trial (NCT03275285).2,3 The goal of the ongoing noninterventional, multinational IONA-MM study is to collect evidence of the efficacy of these 2 regimens in patients with RRMM in a real-world population that may be different from that of the original trials.

Patients were enrolled both prospectively as well as retrospectively if they had received isatuximab less than 3 months prior to enrollment and treatment was determined by their physician independent of enrollment.

A total of 112 patients across 38 sites in 6 countries between August 13, 2020, and February 22, 2022, were included in this first interim analysis. Of these patients, 81 received at least 1 dose of Isa-Pd and 26 received Isa-Kd, while 5 received other isatuximab-containing regimens.1

Compared with the populations of the ICARIA-MM and IKEMA trials, more patients on IONA-MM were at least 75 years old and more had ISS (International Staging System) stage III disease versus stage I or II disease.1-3 A lower percentage of patients who received Isa-Kd had high-risk cytogenetics (12.5%) compared with those in the IKEMA trial (23.5%).1,3 All groups received a median of 3 prior lines of therapy, except for those on IKEMA who received a median of 2 prior lines.1 The Isa-Pd group included 31.5% of patients who had received at least 4 prior lines of therapy versus 37.0% who had in the ICARIA-MM trial, while 23.1% of those in the Isa-Kd group had received at least 4 lines versus only 1.7% in the IKEMA trial.1-3

In the ICARIA-MM trial, 97.4% of patients had been refractory to their last regimen, but this was only true of 58.0% of those who received the Isa-Pd regimen in the real-world population.1,2 However, more patients (73.1%) in the real-world population were refractory to their last regimen before receiving Isa-Kd versus 49.7% in the IKEMA trial.1,3

For those who received Isa-Pd, the median duration of treatment was 5.4 months (range, 0-18.8) and 79.0% continued to receive isatuximab after the data cutoff.1,2 For those who received Isa-Kd, the median duration was 6.2 (range, 0-10.6), and 74.1% continued to receive isatuximab.1,3

Investigators monitored for treatment-emergent adverse events (TEAEs). Among those who received Isa-Pd, 52 patients (64.2%) had any-grade TEAEs, 36 (44.4%) had grade 3 or more TEAEs, and 21 (25.9%) had serious TEAEs. Among those who received Isa-Kd, 16 (61.5%) patients had any-grade TEAEs, 10 (38.5%) had grade 3 or more TEAEs, and 8 (30.8%) had serious TEAEs.1 All of these rates were significantly lower than in the corresponding phase 3 trial.2,3 There were 4 fatal AEs reported in the Isa-Pd, consisting of 2 cases of sepsis, 1 of septic shock, and 1 failure to thrive.1 One fatal AE occurred in the Isa-Kd arm due to pneumonia.

The most common TEAE in the Isa-Pd population was neutropenia, which occurred in 18 of 81 patients (22.2%), 17 (21.0%) of whom had grade 3 or higher cases.1 In the Isa-Kd population, the most common TEAE was diarrhea, which occurred in 4 of 26 patients (15.4%), none of which were grade 3 or higher.

TEAEs led to treatment discontinuation in 6 (7.4%) of those who received Isa-Pd and 3 (11.5%) of those who received Isa-Kd. Overall, isatuximab-containing regimens appeared to have manageable toxicity in a real-world patient population, with low rates of discontinuation.

The IONA-MM trial will continue to gather data on real-world patients with a target sample size of 1100 patients. Upcoming analyses will include efficacy-related primary end points including overall response rate and progression-free survival.

“In conclusion, the IONA-MM study provides real-world evidence to inform the use of isatuximab in patients with RRMM outside of clinical trials and in a wider patient population,” said Martin.

_References:

_{1. Martin T, Beksac M, Cavo M, et al. Real-world experience with isatuximab in patients with relapsed and/or refractory multiple myeloma (RRMM): IONA-MM first interim analysis. Poster presented at: 19th Annual International Myeloma Society (IMS) Annual Meeting; August 25-27, 2022; Los Angeles, CA. Abstract P-258.}