INTERIM ANALYSIS:
21 months median follow-up

SARCLISA + CARFILZOMIB AND DEXAMETHASONE (Kd)

IKEMA: Adverse Reactions for SARCLISA + Kd

Adverse reactions1,2

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

SARCLISA + Kd
Kd
8%
14%
  • The most frequent adverse reactions requiring permanent discontinuation were infections (2.8%, SARCLISA + Kd; 4.9%, Kd)
  • 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%)

The addition of SARCLISA to Kd
did not increase treatment discontinuations due to adverse reactions vs Kd alone

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.

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

Hematology laboratory abnormalities in patients receiving SARCLISA + Kd vs Kd alone1

Laboratory
parameters
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 failure*†

  • 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.

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

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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%).

MedDRA=Medical Dictionary for Regulatory Activities; SMQ=standardized MedDRA query.

Infusion-related reactions (IRRs)1

Incidence and timing of IRRs

A 1st icon.
Across 3 clinical trials, IRRs occurred in 35% of patients receiving SARCLISA (n=206/592). Among these patients, 92% experienced IRRs during the first infusion and 12% experienced them after the first cycle
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Grade 1 IRRs were reported in 6% of patients receiving SARCLISA, grade 2 in 28%, and grade 3 or 4 in 1.2% across the 3 clinical trials

Symptoms of IRRs

A lightning bolt icon.
The most common symptoms (≥5%) of an IRR across the 3 clinical trials included dyspnea and cough
  • Anaphylactic reactions occurred in <1% of patients across the 3 clinical trials
An exclamation point icon.
Serious IRRs, including life-threatening anaphylactic reactions, have occurred with SARCLISA treatment. Severe signs and symptoms included cardiac arrest, hypertension, hypotension, bronchospasm, dyspnea, angioedema, and swelling

Infusion interruption and discontinuation due to IRRs

A hand icon.
Infusion interruption of SARCLISA occurred in <1% of patients across the 3 clinical trials; of these patients, 26% experienced interruptions due to IRRs
An x icon.
SARCLISA alone was discontinued due to IRRs in 1% of patients across the 3 clinical trials

RRMM=relapsed or refractory multiple myeloma.

Managing IRRs1,4

  • To decrease the risk and severity of IRRs, premedicate patients prior to SARCLISA infusion with acetaminophen, H2 antagonists, diphenhydramine or equivalent, and dexamethasone
  • Monitor vital signs frequently during the entire SARCLISA infusion

Defining IRR grades4

IV=intravenous; NSAID=nonsteroidal anti-inflammatory drug.

Dose modifications1

Dose delay may be required to allow for recovery of blood counts in the event of hematological toxicity. For dosing instructions for combination agents administered with SARCLISA, refer to the study design description for IKEMA and the respective manufacturer’s Prescribing Information.

No dose reduction of SARCLISA
is recommended

View the premedication information for SARCLISA

Dosing

Other adverse reactions1

Infections

  • SARCLISA can cause severe, life-threatening, or fatal infections. In patients who received SARCLISA at the recommended dose in ICARIA-MM, IKEMA, and IMROZ (N=592), serious infections, including opportunistic infections, occurred in 46%, grade 3 or 4 infections occurred in 43%, and fatal infections occurred in 4.7%. The most common type of serious infection reported was pneumonia (32%)
  • Monitor patients for signs and symptoms of infection prior to and during treatment with SARCLISA and treat appropriately. Administer prophylactic antimicrobials according to guidelines

Neutropenia

  • SARCLISA can cause neutropenia. In 3 clinical trials, in patients treated with SARCLISA (N=592), neutropenia based on laboratory values occurred in 81%, with grade 3 or 4 occurring in 52%. Neutropenic infections occurred in 12% of patients, with grade 3 or 4 in 4.9%, and febrile neutropenia in 4%
  • Monitor complete blood cell counts periodically during treatment
  • Consider the use of antibacterial and antiviral prophylaxis during treatment
  • Monitor patients with neutropenia for signs of infection
  • If grade 4 neutropenia occurs, delay SARCLISA dose until neutrophil count recovery to at least 1 × 109/L, and provide supportive care with growth factors, according to institutional guidelines

Second primary malignancies

  • Monitor patients for the development of second primary malignancies
  • The incidence of second primary malignancies is increased in patients treated with regimens that contain SARCLISA
    • Across 3 clinical trials in patients treated with SARCLISA (N=592), second primary malignancies occurred in 12% of patients
    • In the IKEMA study, at a median follow-up time of 57 months, second primary malignancies occurred in 10% of patients in the SARCLISA + Kd arm and in 8% of patients in the Kd arm
  • The most common (≥1%) second primary malignancies across 3 clinical trials (N=592) included skin cancers (7% with SARCLISA-containing regimens and 3.1% with comparative regimens) and solid tumors other than skin cancer (4.6% with SARCLISA-containing regimens and 2.9% with comparative regimens). Patients with non-melanoma skin cancer continued treatment after resection of the skin cancer in IKEMA

Laboratory test interference

SARCLISA, an anti-CD38 antibody, may interfere with blood bank serological tests with false-positive reactions in indirect antiglobulin tests (indirect Coombs tests), antibody detection (screening) tests, antibody identification panels, and antihuman globulin crossmatches in patients treated with SARCLISA. This interference with the indirect Coombs test may persist for approximately 6 months after the last infusion of SARCLISA.

  • Conduct blood type and screen tests in patients before the first infusion of SARCLISA
  • Consider phenotyping prior to starting treatment with SARCLISA
  • If treatment with SARCLISA has already begun, inform the blood bank that the patient is receiving SARCLISA, and SARCLISA interference with blood compatibility testing can be resolved using dithiothreitol-treated red blood cells (RBCs). If an emergency transfusion is required, non–cross-matched ABO/RhD-compatible RBCs can be given as per local blood bank practices
Dosing