SARCLISA + POMALIDOMIDE AND DEXAMETHASONE (Pd)

ICARIA-MM: Adverse Reactions for SARCLISA + Pd

Discontinuation rates^1,2

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

SARCLISA + Pd

7^%

12^%

Dosage interruptions due to an adverse reaction occurred in 31% of patients who received SARCLISA + Pd

Discontinuations from treatment due to infection were reported in 2.6% of patients receiving SARCLISA + Pd vs 5% of patients receiving Pd alone
The most frequent adverse reaction requiring dosage interruption was IRR (28%)

The addition of SARCLISA to Pd
did not increase treatment discontinuations due to adverse reactions vs Pd alone^1,2

IRR=infusion-related reaction.

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

Adverse reactions

SARCLISA
+ Pd
(n=152)

All grades

Grade 3

Grade 4

Pd
(n=149)

All grades

Grade 3

Grade 4

General disorders and administration site conditions

IRR^a

38^%

1.3^%

0^%

Infections

Upper respiratory tract infection^b

57^%

9^%

0^%

42^%

3.4^%

0^%

Pneumonia^c

31^%

22^%

3.3^%

23^%

16^%

2.7^%

Blood and lymphatic system disorders

Febrile neutropenia

12^%

11^%

1.3^%

2^%

1.3^%

0.7^%

Respiratory, thoracic, and mediastinal disorders

Dyspnea^d

17^%

5^%

0^%

12^%

1.3^%

0^%

Gastrointestinal disorders

Diarrhea

26^%

2^%

0^%

19^%

0.7^%

0^%

Nausea

15^%

0^%

9^%

0^%

Vomiting

12^%

1.3^%

0^%

3.4^%

0^%

^aIRR includes IRR, cytokine release syndrome, and drug hypersensitivity.

^bUpper respiratory tract infection includes bronchiolitis, bronchitis, bronchitis viral, chronic sinusitis, fungal pharyngitis, influenza-like illness, laryngitis, nasopharyngitis, parainfluenzae virus infection, pharyngitis, respiratory tract infection, respiratory tract infection viral, rhinitis, sinusitis, tracheitis, upper respiratory tract infection, and upper respiratory tract infection bacterial.

^cPneumonia includes atypical pneumonia, bronchopulmonary aspergillosis, pneumonia, pneumonia haemophilus, pneumonia influenzal, pneumonia pneumococcal, pneumonia streptococcal, pneumonia viral, candida pneumonia, pneumonia bacterial, haemophilus infection, lung infection, pneumonia fungal, and Pneumocystis jirovecii pneumonia.

^dDyspnea includes dyspnea, dyspnea exertional, and dyspnea at rest.

Serious adverse reactions^1,2

Serious adverse reactions occurred in 62% of patients receiving SARCLISA + Pd
- Serious adverse reactions in >5% of patients who received SARCLISA + Pd included pneumonia (26%), upper respiratory tract infection (7%), and febrile neutropenia (7%)
Fatal adverse reactions occurred in 11% of patients in the SARCLISA + Pd arm (those that occurred in >1% of patients were pneumonia and other infections [3%]) vs 11% in the Pd arm

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

Laboratory
parameters

SARCLISA
+ Pd
(n=152)

All grades

Grade 3

Grade 4

Pd
(n=149)

All grades

Grade 3

Grade 4

Hemoglobin decreased

99^%

32^%

0^%

97^%

28^%

0^%

Neutrophils decreased

96^%

24^%

61^%

92^%

38^%

31^%

Lymphocytes decreased

92^%

42^%

13^%

92^%

35^%

8^%

Platelets decreased

84^%

14^%

16^%

79^%

9^%

15^%

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.

Infusion-related reactions (IRRs)¹

Incidence and timing of IRRs

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

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

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

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

Infusion interruption of SARCLISA occurred in <1% of patients across the 3 clinical trials; of these patients, 26% experienced interruptions due to IRRs

SARCLISA alone was discontinued due to IRRs in 1% of patients across the 3 clinical trials

Managing IRRs^1,3

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

Grade 1 IRRs

No interruption or intervention is indicated.

Grade 2-3 IRRs

Interrupt SARCLISA infusion and provide appropriate medical management.

If symptoms improve to grade ≤1, restart SARCLISA infusion at half of the initial infusion rate, with supportive care as needed, and closely monitor patients.

If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally, as shown in the infusion rate table on the Dosing page

If symptoms do not improve to grade ≤1 after interruption of SARCLISA infusion, persist or worsen despite appropriate medications, or require hospitalization, permanently discontinue SARCLISA and institute appropriate management.

Grade 4 IRRs

Permanently discontinue SARCLISA and institute appropriate management.

Grade 1 IRRs

No interruption or intervention is indicated.

Grade 2-3 IRRs

Interrupt SARCLISA infusion and provide appropriate medical management.

If symptoms improve to grade ≤1, restart SARCLISA infusion at half of the initial infusion rate, with supportive care as needed, and closely monitor patients.

If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally, as shown in the infusion rate table on the Dosing page

Grade 4 IRRs

Permanently discontinue SARCLISA and institute appropriate management.

Defining IRR grades³

Grade 1

Mild transient reaction.

Grade 2

Therapy or infusion interruption indicated, but IRR responds promptly to symptomatic treatment (eg, antihistamines, NSAIDs, narcotics, IV fluids); prophylactic medications indicated for ≤24 hours.

Grade 3

Prolonged (ie, not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae.

Grade 4

Life-threatening consequences; urgent intervention indicated.

Grade 1

Mild transient reaction.

Grade 2

Therapy or infusion interruption indicated, but IRR responds promptly to symptomatic treatment (eg, antihistamines, NSAIDs, narcotics, IV fluids); prophylactic medications indicated for ≤24 hours.

Grade 3

Grade 4

Life-threatening consequences; urgent intervention indicated.

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 ICARIA-MM 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 ICARIA-MM, at a median follow-up time of 52 months, second primary malignancies occurred in 7% of patients in the SARCLISA + Pd arm and in 2% of patients in the Pd 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 ICARIA-MM

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

ICARIA-MM: Adverse Reactions for SARCLISA + Pd

Discontinuation rates1,2

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

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

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

Serious adverse reactions1,2

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

Infusion-related reactions (IRRs)1

Incidence and timing of IRRs

Symptoms of IRRs

Infusion interruption and discontinuation due to IRRs

Managing IRRs1,3

Defining IRR grades3

Dose modifications1

No dose reduction of SARCLISAis recommended

View the premedication information for SARCLISA

Other adverse reactions1

Infections

Neutropenia

Second primary malignancies

Laboratory test interference

Discontinuation rates^1,2

The addition of SARCLISA to Pd
did not increase treatment discontinuations due to adverse reactions vs Pd alone^1,2

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

Serious adverse reactions^1,2

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

Infusion-related reactions (IRRs)¹

Managing IRRs^1,3

Defining IRR grades³

Dose modifications¹

No dose reduction of SARCLISA
is recommended

Other adverse reactions¹