FINAL ANALYSIS:
44 months median follow-up

SARCLISA + CARFILZOMIB
AND DEXAMETHASONE (Kd)

IKEMA: SARCLISA + Kd vs
Kd Alone in RRMM

Unprecedented results: ~42 months mPFS with SARCLISA + Kd

Longest ever reported in a phase 3 trial that included lenalidomide-refractory patients1-7*

*Based on a review of published phase 3 trials that included lenalidomide-refractory patients with RRMM. Interpret with caution, as various factors, including patient population, differ between trials.

PFS results were assessed by an IRC, based on central laboratory data for M-protein, and central radiologic imaging review using IMWG criteria. A preplanned interim analysis was conducted when 65% of 159 PFS events were observed. P value is not reported as this is a non-inferential analysis of the primary endpoint that was met at the time of the interim analysis.1,8

Superior PFS vs Kd at
interim analysis

(median follow-up of 20.7 months)1

SARCLISA + Kd: mPFS NR
Kd: mPFS 20.27 months1

HR=0.548
(95% CI: 0.37, 0.82; P=0.0032)1

Final analysis: A prespecified final analysis was conducted when 159 PFS events were observed, with a median follow-up of 44 months.2

The median duration of treatment was 94 weeks with SARCLISA + Kd vs 62 weeks with Kd alone. The median time to next treatment was 44.91 months (95% CI: 31.61, NR) in the SARCLISA + Kd arm vs 25.0 months (95% CI: 17.94, 31.31) with Kd alone8,9

IMWG=International Myeloma Working Group; IRC=independent response committee; mPFS=median progression-free survival; M-protein=monoclonal protein; NR=not reached; PFS=progression-free survival; RRMM=relapsed or refractory multiple myeloma.

NCCN

CATEGORY 1
PREFERRED

National Comprehensive Cancer Network® (NCCN®) recommends isatuximab-irfc (SARCLISA) in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Multiple Myeloma as a Category 1 Preferred option in combination with carfilzomib and dexamethasone or with pomalidomide and dexamethasone10:

  • For early relapses (1-3 prior therapies)†
  • Option for patients refractory to either lenalidomide or bortezomib

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Recommendation for isatuximab-irfc (SARCLISA) in combination with carfilzomib and dexamethasone based on results of interim analysis.

†After 2 prior therapies including lenalidomide and a proteasome inhibitor for isatuximab-irfc in combination with pomalidomide and dexamethasone.

NCCN=National Comprehensive Cancer Network® (NCCN®).

Explore a patient profile for SARCLISA + Kd at first relapse

Review Patient Profile

Patients in the IKEMA trial achieved deep responses2‡

High rates of ≥VGPR were seen in IKEMA

As ORR did not reach statistical significance, ≥VGPR and CR were not tested for significance

Interim analysis (20.7 months median follow-up)1,8

  • ORR:
    • — 86.6% (95% CI: 0.81, 0.91) with SARCLISA + Kd
    • — 82.9% (95% CI: 0.75, 0.89) with Kd alone
    • — P=0.3859; 95% CI estimated using the Clopper-Pearson method
  • ≥VGPR: 72.6% with SARCLISA + Kd vs 56.1% with Kd alone
  • CR: 39.7% with SARCLISA + Kd vs 27.6% with Kd alone
  • MRD-: 30% with SARCLISA + Kd (95% CI: 0.23, 0.37) vs 13% with Kd alone (95% CI: 0.08, 0.20)

The median time to first response among responders was 1.08 months in the SARCLISA + Kd arm and 1.12 months in the Kd arm.8

‡A response of ≥VGPR.

asCR, CR, VGPR, and PR were evaluated by the IRC using the IMWG response criteria. Results are based on a prespecified final analysis with a median follow-up time of 44 months.1

CR=complete response; MRD-=minimal (or measurable) residual disease negative/negativity; ORR=overall response rate; PR=partial response; sCR=stringent complete response; VGPR=very good partial response.

6 out of 10 patients in CR achieved MRD- with SARCLISA + Kd2,9

Rate of MRD- by adaptive NGS at 10-5§

Interim analysis (20.7 months median follow-up): MRD- rate in the ITT population was 30% with SARCLISA + Kd (95% CI: 0.23, 0.37) vs 13% with Kd alone (95% CI: 0.08, 0.20)1,8

In IKEMA, achieving MRD- translated into prolonged PFS8

PFS by MRD status and treatment arm at the final analysis

PFS results were assessed by an IRC, based on central laboratory data for M-protein, and central radiologic imaging review using the IMWG criteria.1

The addition of SARCLISA to Kd also improved PFS in patients who remained MRD+ (HR=0.71, 95% CI: 0.50, 1.00)8

Study limitations

According to the FDA, using MRD to assess clinical benefit of a multiple myeloma treatment should only be assessed in patients who achieve a CR or sCR. In the IKEMA trial, MRD was assessed in patients who achieved ≥VGPR. Additionally, there was an amount of missing data that did not meet the FDA’s threshold for label inclusion. This analysis requires cautious interpretation and clinical significance of these data is unknown.

§Based on a sensitivity level of 10-5 by NGS in patients who achieved ≥VGPR.8

ITT=intent to treat; MRD+=minimal (or measurable) residual disease positive/positivity; NGS=next-generation sequencing.

Subgroup data for SARCLISA + Kd8

Consistent PFS results were seen across almost all subgroups with SARCLISA + Kd

A forest plot shows the PFS data for patient subgroups receiving SARCLISA + Kd vs Kd alone in the IKEMA trial. A forest plot shows the PFS data for patient subgroups receiving SARCLISA + Kd vs Kd alone in the IKEMA trial.

aHigh-risk cytogenetic status was defined as the presence of del(17p) and/or t(4;14) and/or t(14;16). Chromosomal abnormality was considered positive if present in ≥30% of analyzed plasma cells, except for del(17p), where the threshold was ≥50%; please note that due to the low number of patients with t(14;16), the HR could not be calculated.

b1q21+ was also analyzed and was considered positive if there were ≥3 copies in ≥30% of analyzed plasma cells.

Study limitations

All subgroups were prespecified except the lenalidomide-refractory subgroup. Subgroups were not powered to show differences between treatment arms.

ASCT=autologous stem cell transplant; IMiD=immunomodulatory drug; ISS=International Staging System.

Reduction in the risk of disease progression in patients treated with SARCLISA + Kd vs Kd alone

A silhouette icon of a person.

Older age ≥65 years of age

41% A downward-pointing arrow.

HR=0.59 (95% CI: 0.37, 0.95)

An icon of an arrow deflecting off a surface.

Refractory to lenalidomide

43% A downward-pointing arrow.

HR=0.57 (95% CI: 0.34, 0.97)

An icon of a pair of kidneys.

Renal impairment eGFR <60 mL/
min/1.73 m2

33% A downward-pointing arrow.

HR=0.67 (95% CI: 0.30, 1.51)

An icon of a chromosome.

Presence of 1q21+

38% A downward-pointing arrow.

HR=0.62 (95% CI: 0.38, 1.01)

Study limitations

All subgroups were prespecified except the lenalidomide-refractory subgroup. Subgroups were not powered to show differences between treatment arms.

1q21+ was considered positive if there were ≥3 copies in ≥30% of analyzed plasma cells.

eGFR=estimated glomerular filtration rate.

IKEMA trial: SARCLISA + Kd vs Kd alone

Evaluated in 302 patients in a phase 3, multicenter, multinational, randomized, open-label study1,8

Patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy (N=302)
Randomized 3:2

sarclisaa + Kdb
(n=179)

Kdb
(n=123)

Treatment was administered in 28-day cycles until disease progression or unacceptable toxicity.

PRIMARY ENDPOINT: PFSǁ

Key secondary endpoints: ORR, ≥VGPR, CR, MRD negativity, OS

aSARCLISA 10 mg/kg was administered as an IV infusion weekly in the first cycle and every 2 weeks thereafter.

bCarfilzomib was administered as an IV infusion during cycle 1 at a dose of 20 mg/m2 on days 1 and 2, and at 56 mg/m2 on days 8, 9, 15, and 16; during subsequent cycles, it was administered at 56 mg/m2 on days 1, 2, 8, 9, 15, and 16. Dexamethasone (IV on the days of SARCLISA and/or carfilzomib infusions, and orally on the other days) 20 mg was given on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle.

IIPFS results were assessed by an IRC, based on central laboratory data for M-protein, and central radiologic imaging review using the IMWG criteria. An interim analysis was conducted when 65% of the 159 PFS events (ie, 103 events) were observed. A prespecified final analysis was conducted when 159 PFS events were observed, with a median follow-up of 44 months.

IV=intravenous; OS=overall survival.

The IKEMA trial included a broad and diverse patient population1,8,11

Patient factors

28%
≥70 years of age
20%
Impaired renal functiona
24%
High cytogenetic risk

Treatment history

90%/
43%
Prior PI/lenalidomide
33%
Refractory to lenalidomide
61%
Prior ASCT

Baseline characteristics were balanced across both treatment arms

Baseline characteristics
SARCLISA + Kd
(n=179)
Kd
(n=123)
Age, years
 
 
Median (range)
65 (37-86)
63 (33-90)
<70
71%
72%
≥70
29%
28%
Renal impairmenta
 
 
≥60 mL/min/1.73 m2
68%
76%
<60 mL/min/1.73 m2
24%
15%
≥15-<30 mL/min/1.73 m2
2%
2%
ECOG PS
 
 
0 or 1
94%
96%
2
6%
4%
ISS stage at study entry
I
50%
58%
II
35%
25%
III
15%
16%
Cytogenetic abnormality at baseline
Highb
23%
25%
    del(17p)
10%
13%
    t(4;14)
12%
16%
    t(14;16)
3%
0%
Standard
64%
63%
Unknown or missing
13%
11%
1q21+c
42%
42%
Prior lines of therapyd
 
 
Median (range)
2 (1-4)
2 (1-4)
1
44%
45%
Prior therapies
 
 
PI
93%
85%
IMiD
76%
81%
Lenalidomide
40%
48%
Patient refractory to
 
 
IMiD
44%
47%
Lenalidomide
32%
34%
IMiD + PI
20%
22%
Previous ASCT
 
 
Yes
65%
56%

aImpaired renal function is defined as eGFR <60 mL/min/1.73 m2.1

bHigh-risk cytogenetic status is defined as the presence of del(17p) and/or t(4;14) and/or t(14;16). Chromosomal abnormality was considered positive if present in ≥30% of analyzed plasma cells, except for del(17p), where the threshold is ≥50%.8

c1q21+ was also analyzed and was considered positive if there were ≥3 copies in ≥30% of analyzed plasma cells.8

dInclusion criteria for the IKEMA study specified 1 to 3 prior lines of therapy; however, 3 patients (1.7%) and 2 patients (1.6%) had >3 prior lines in the SARCLISA + Kd and Kd arms, respectively.8

ECOG PS=Eastern Cooperative Oncology Group performance status; PI=proteasome inhibitor.

See Who May Be Appropriate for SARCLISA + Kd View IKEMA Safety Data
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