Meaningful progression-free survival and safety elicited with isatuximab plus pomalidomide and dexamethasone treatment in real-world multiple myeloma population.
Isatuximab-irfc (Sarclisa) with pomalidomide (Pomalyst) and dexamethasone resulted in meaningful effectiveness and demonstrated a manageable safety profile in adult patients with multiple myeloma who have received at least 2 prior therapies, according to real-world data from the IMAGE trial.
This is the first study to report meaningful progression-free survival (PFS) for the combination in this patient population at first relapse, suggesting the combination to be a potential new treatment option in earlier lines of therapy. The real-world data were compared with the ICARIA-MM clinical trial findings (NCT02990338) and supports isatuximab with pomalidomide, and dexamethasone as a standard-of-care treatment for relapsed/refractory multiple myeloma.
In the 294 patients assessed in the IMAGE trial, the median PFS was 12.4 months (95% CI, 9.0-15.0) compared with 10.9 months (95% CI, 7.9-15.5 in a retrospective study population evaluated in the United Kingdom (UK), and 11.1 months (95% CI, 7.8-13.8 months) in the ICARIA-MM trial.
Median PFS was not reached (NR; 95% CI, 9.6-NR), 13.6% (95% CI, 10.2-NR), and 7.6 (95% CI, 4.4-11.8) among those who received 1, 2, or 3 or more lines of therapy, respectively. in the IMAGE study. The median time to next treatment was 15.2 months in the IMAGE study vs 15.5 months in ICARIA-MM.
Isatuximab is an anti-CD38 monoclonal antibody which induces myeloma cell death through targeting a specific epitope on CD38. Data from the phase 3 ICARIA-MM study examining isatuximab in combination with pomalidomide and dexamethasone was the basis of its approval in patients with relapsed/refractory multiple myeloma who had received 2 or more prior therapies including lenalidomide (Revlimid) and a proteasome inhibitor.
Prior to its approval, isatuximab was available in France under early access programs (EAP). This planned interim analysis of the non-interventional, retrospective IMAGE study describes baseline characteristics, PFS, and safety among French pts with RRMM treated with isatuximab plus pomalidomide and dexamethasone under the EAPs.
Data from medical records of patients aged 18 years and older with relapsed/refractory multiple myeloma who received 1 or more dose of isatuximab under the EAPs was collected. Effectiveness analysis was restricted to pts with ≥ 1 year of follow-up after Isa initiation. PFS was defined as the time from the start of isatuximab with pomalidomide and dexamethasone to date of disease progression (as reported in the medical record) or death. Verbatim terms for AEs were coded using the Medical Dictionary for Regulatory Activities; AEs were not graded for severity.
In the effectiveness population, 294 patients from 62 various study sites across France who met all inclusion criteria and who had received 1 or more dose of isatuximab under the EAPs were enrolled between July 29, 2019 and September 1, 2020. The safety population included 299 patients who received 1 or more doses of isatuximab.
The IMAGE study included patients who were daratumumab-refractory (19.1%) as well as patients who had only received 1 prior line of therapy (10.2%). In the IMAGE trial, patients had received fewer prior lines of therapy with a median of 2 compared to those in the ICARIA-MM trial who had a median of 3. Additionally, a lower proportion of patients in the IMAGE effectiveness population were refractory to lenalidomide at 73% compared with 94% and last line of therapy at 70% vs 97%.
The median age of patients enrolled in IMAGE was 70.2 (range, 40-90) vs 68.0 (range, 36-83) in ICARIA-MM. In IMAGE, 46 patients (13.6%) had stage I disease, 41 (13.9%) had stage II, 107 (36.4%) had stage III, and the other 100 (34%) were unaware. Further, 43 patients (13.6%) were high cytogenetic risk and 134 (45.6%) were standard, and 124 patients had an ECOG performance status of 0, 1, or 2.
By the time of the data cutoff, the median duration of isatuximab exposure for patients enrolled in the IMAGE trial was 38.7 (range, 14.0-65.4) weeks. The overall response rate was lowest in the IMAGE study at 46.3% vs 63% in the ICARIA-MM trial and 66.4% in the UK-wide, real-world study. Further, very good partial responses and partial responses were comparable between IMAGE and the UK study (27.9% vs 31.8% and 41.5% vs 34.6%).
The median overall survival was also not reached in the IMAGE study (95% CI, 18.9-NR) while it was 18.8 months (95% CI, 14.4-NR) in the UK-wide, real-world study, and 24.6% (95% CI, 20.3-31.3) in ICARIA-MM.
Among the patients receiving subsequent therapy, 18.2% were given carfilzomib/dexamethasone while 12.1% were given belantamab mafodotin. This median PFS was 5.8 (range, 4.2-7.1 months).
A total of 73 (24.8%) patients permanently discontinued isatuximab, most commonly due to disease progression. Additionally, 33 patients (11.2%) received granulocyte-colony stimulating factor during 100% of their treatment cycles while 61 (20.7%) received it during 50% to less than 100% of cycles, and 200 patients received it during less than 50% of cycles.
There was at least 1 adverse event (AE) reported in the 79 patients (26.4%) with the most common AE being neutropenia, found in 28 patients (9.4%). Additionally, AEs led to permanent isatuximab discontinuation in 4 patients (1.3%).
There were not any patients who experienced viral re-infection during treatment with isatuximab and 1 patient (0.3%) developed a secondary primary malignancy.
Overall, the real-world data showed isatuximab, pomalidomide, and dexamethasone to demonstrate meaningful PFS and show a manageable safety profile. Though there were slight differences in study populations between the IMAGE trial and the ICARIA-MM trial, the similar median PFS results support use of the combination as a standard of care for patients with relapsed/refractory multiple myeloma.