IN THE LITERATURE
Adding Isatuximab to Dexamethasone-Pomalidomide
Combination Improves Progression-Free Survival in
Pretreated Myeloma
Treatment with the investigational anti-CD38 monoclonal antibody
isatuximab plus the combination of pomalidomide and low-dose
dexamethasone (Pd) led to a median progression-free survival (PFS)
of 11.5 months in patients with relapsed and refractory multiple my-
eloma (MM), according to findings from the phase III ICARIA-MM
trial that were published in The Lancet. This was nearly twice as long
as the median PFS in patients who were treated with Pd alone, re-
ported lead author Michel Attal, MD, from the Institut Universitaire
du Cancer Toulouse Oncopole in Toulouse, France, and colleagues.
“ICARIA-MM is the first positive randomized, phase III
study adding an anti-CD38 antibody, isatuximab, to a
pomalidomide-dexamethasone backbone therapy for
relapsed and refractory MM,” Dr. Attal and authors wrote.
In addition to the improvements in PFS and response rates,
the addition of isatuximab “was well tolerated, with no
increase in treatment discontinuations or incidence of fatal
events,” they noted.
The 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]).
Patients whose disease was refractory to a previous anti-
CD38 monoclonal antibody were excluded.
Participants were randomized 1:1 to receive isatuximab
plus Pd (n=154) or Pd alone (n=153). Pd was administered in
28-day cycles of pomalidomide 4 mg on days 1 through 21
and dexamethasone 40 mg (20 mg if >75 years) weekly, until
disease progression or unacceptable toxicity. Isatuximab 10
mg/kg was administered through intravenous infusion for
the first 4 weeks, then every 2 weeks thereafter.
Patient characteristics were well-balanced between
the treatment groups: Median age was 67 years (range =
59-74), and the median number of prior lines of therapy was
3 (range = 2-4). Nearly all patients in the isatuximab and
Pd-alone groups were refractory to their last line of therapy
(97% and 99%, respectively).
At a median follow-up of 11.6 months (interquartile
range [IQR] = 10.1-13.9), the median PFS was 11.5 months
in the isatuximab-treated group, compared with 6.5 months
in the Pd-treated group (hazard ratio = 0.596; 95% CI 0.44-
0.81; p=0.001).
The PFS benefit with isatuximab was observed across
all prespecified subgroups, the authors noted, including
those with high cytogenetic risk disease and those with
lenalidomide-refractory disease ( TABLE ).
Isatuximab also appeared to increase the rates of
response and depth of response, compared with Pd alone.
More patients in the isatuximab-treated group achieved a
complete response (5% vs. 1%), very good partial response
(27% vs. 7%), or partial response (29% vs. 27%; p<0.0001 for
all comparisons).
“Responses occurred faster and were more durable in
the [isatuximab-Pd] group than the Pd group,” the investi-
gators reported, with a median time to first response of 35
days (IQR=32-60) versus 58 days (IQR=32-87). In addition,
responses lasted longer in the isatuximab group (13.3
months vs. 11.1 months).
Overall, safety results were similar between both treat-
ment groups, with the exception of infusion reactions,
which occurred exclusively in the isatuximab group (56%).
Most of these were reversible and occurred with the first
infusion of isatuximab.
There appeared to be more grade ≥3 adverse events
(AEs) in the isatuximab group than the Pd group (86.8% vs.
70.5%). Incidence of hematologic AEs were similar between
the groups, although grade 4 neutropenia was more fre-
quent in the isatuximab group (61% vs. 31%). However, more
patients in the Pd-alone group than the isatuximab group
discontinued treatment due to AEs (12.8% vs. 7.2%).
Fatal AEs were reported in 12 patients (8%) in the isa-
tuximab group and 14 (9%) in the Pd group. Deaths due to
treatment-related AEs were reported in 1 patient (<1%) in
the isatuximab group (sepsis) and 2 (1%) in the Pd group
(pneumonia and urinary tract infection).
Subgroup Analyses of Progression-Free
Survival
TABLE.
Characteristic
Hazard ratio
p Value
Previous lines of therapy
2-3 0.59 (0.40–0.88)
>3 0.59 (0.36–0.98)
0.9583
Cytogenetic risk
High 0.66 (0.33–1.28)
Standard 0.62 (0.42–0.93)
0.9990
Refractory to lenalidomide
Yes 0.59 (0.43–0.82)
No 0.18 (0.02–1.49)
0.3006
ISS stage at study entry
I 0.66 (0.38–1.13)
II 0.54 (0.32–0.93)
III 0.64 (0.36–1.11)
0.7901
ISS = International Staging System
March 2020
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