INTERIM ANALYSIS:
21 months
 median
follow-up

IKEMA: SARCLISA + CARFILZOMIB AND DEXAMETHASONE (Kd)

Adverse Reactions for SARCLISA + Kd

Adverse Reactions Laboratory Abnormalities Final Analysis: Safety Data

Discontinuation rates

Permanent treatment discontinuation due to adverse reactions (grades 1 to 4)1,2

SARCLISA + Kd
Kd
8%
14%
  • The most frequent adverse reactions requiring permanent discontinuation were infections (2.8%, SARCLISA + Kd; 4.9%, Kd)1,2
  • Dosage interruptions due to an adverse reaction occurred in 33% of patients who received SARCLISA. The most frequent adverse reaction requiring dosage interruption was IRR (30%)1

The addition of SARCLISA to Kddid not increase treatment
discontinuations due to adverse reactions
vs Kd alone1,2

Adverse reactions (≥10%) in patients receiving SARCLISA + Kd with a
difference between arms of ≥5% compared with Kd alone1

Adverse reactions
SARCLISA + Kd
(n=177)
All grades
All grades
Grade 3
Grade 4
Kd (n=122)
All grades
All grades
Grade 3
Grade 4
General disorders and administration site conditions
IRRa
46%
0.6%
0%
3.3%
0%
0%
Fatigueb
42%
5%
0%
32%
3.3%
0%
Infections
Upper respiratory tract infectionc
67%
9%
0%
57%
7%
0%
Pneumoniad
36%
19%
3.4%
30%
15%
2.5%
Bronchitise
24%
2.3%
0%
13%
0.8%
0%
Vascular disorders
Hypertensionf
37%
20%
0.6%
32%
18%
1.6%
Respiratory, thoracic, and mediastinal disorders
Dyspneag
29%
5%
0%
24%
0.8%
0%
Coughh
23%
0%
0%
15%
0%
0%
Gastrointestinal disorders
Diarrhea
36%
2.8%
0%
29%
2.5%
0%
Vomiting
15%
1.1%
0%
9%
0.8%
0%

aIRR includes IRR, cytokine release syndrome, and hypersensitivity.

bFatigue includes fatigue and asthenia.

cUpper respiratory tract infection includes acute sinusitis, chronic sinusitis, H1N1 influenza, H3N2 influenza, influenza, laryngitis, laryngitis viral, nasal herpes, nasopharyngitis, pharyngitis, pharyngotonsillitis, respiratory syncytial virus infection, rhinitis, sinusitis, sinusitis bacterial, tonsillitis, tracheitis, upper respiratory tract infection, viral rhinitis, respiratory tract infection, respiratory tract infection viral, influenza-like illness, parainfluenzae virus infection, respiratory tract infection bacterial, and viral upper respiratory tract infection.

dPneumonia includes atypical pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, Pneumocystis jirovecii pneumonia, pneumonia, pneumonia influenzal, pneumonia legionella, pneumonia pneumococcal, pneumonia respiratory syncytial viral, pneumonia streptococcal, pneumonia viral, pulmonary sepsis, and pulmonary tuberculosis.

eBronchitis includes bronchitis, bronchitis viral, respiratory syncytial virus bronchitis, bronchitis chronic, and tracheobronchitis.

fHypertension includes hypertension, blood pressure increased, and hypertensive crisis.

gDyspnea includes dyspnea and dyspnea exertional.

hCough includes cough, productive cough, and allergic cough.

IRR=infusion-related reaction.

See the types of IRRs that occurred in the IKEMA trial and how to manage them

IRRs/Other Safety Information

Serious adverse reactions1,2

  • Serious adverse reactions occurred in 59% of patients receiving SARCLISA + Kd
    • The most frequent serious adverse reactions in >5% of patients who received SARCLISA + Kd were pneumonia (25%) and upper respiratory tract infections (9%)
  • Fatal adverse reactions occurred in 3.4% of patients receiving SARCLISA + Kd (those occurring in >1% of patients were pneumonia in 1.7% and cardiac failure in 1.1% of patients) vs 3.3% in the Kd arm
Laboratory
parameter
SARCLISA + Kd
(n=177)
All grades
All grades
Grade 3
Grade 4
Kd (n=122)
All grades
All grades
Grade 3
Grade 4
Hemoglobin decreased
99%
22%
0%
99%
20%
0%
Lymphocytes decreased
94%
52%
17%
95%
43%
14%
Platelets
decreased
94%
19%
11%
88%
16%
8%
Neutrophils decreased
55%
18%
1.7%
43%
7%
0.8%

The denominator used to calculate the percentages was based on the safety population.

Complete blood cell counts should be monitored periodically during treatment. Patients with neutropenia should be monitored for signs of infection. In case of infection, appropriate standard therapy should be instituted. Antibacterial and antiviral prophylaxis can be considered during treatment.

Cardiac failure1*†

  • In IKEMA, cardiac failure was reported in 7% of patients in the SARCLISA + Kd group (grade ≥3, 4%) and in 7% of patients in the Kd group (grade ≥3, 4.1%)
  • In IKEMA, serious cardiac failure was observed in 4% of patients in the SARCLISA + Kd group and in 3.3% of patients in the Kd group

*Cardiac failure included cardiac failure, cardiac failure congestive, cardiac failure acute, cardiac failure chronic, left ventricular failure, and pulmonary edema.1

†See the current Prescribing Information for carfilzomib for more information.

Safety Update From the IKEMA Final Analysis3

SARCLISA + Kd
(n=177)
Kd (n=122)
Median treatment exposure
94 weeks
62 weeks
Serious adverse reactions
70.1%
59.8%
Fatal adverse reactions
5.6%
4.9%
Cardiac failure, grade ≥3 (any classa)
4.5%
4.1%
Permanent discontinuation
due to adverse reactions (grades
1 to 4)
12.4%
18.0%

aGrouping using MedDRA SMQ cardiac failure narrow terms.

The safety profile at the longer follow-up remained consistent with the interim analysis, with the most frequent adverse reactions (all grades) in the SARCLISA + Kd group being IRRs (45.8%), diarrhea (39.5%), hypertension (37.9%), and upper respiratory tract infections (37.3%).

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