This website contains promotional content and is intended for Healthcare Professionals based in the United Kingdom only. Some content is only relevant to HCPs practising in Great Britain (England, Scotland, Wales). This website is optimised for desktop use, and some features may perform differently on mobile devices.

Adverse event reporting can be found at the bottom of the page.

SARCLISA®

(isatuximab)

This is intended for HCPs practising in Great Britain (England, Scotland, Wales) only.

Profile

For adult patients with relapsed and refractory multiple myeloma improve outcome with SARCLISA® in combination with pomalidomide + dexamethasone (Pd) vs. Pd.*1,2 ICARIA-MM: The first positive Phase 3 trial of an anti-CD38 monoclonal antibody triplet in relapsed and refractory multiple myeloma (RRMM).2

*SARCLISA® + Pd significantly increased mPFS vs. Pd alone (11.53 vs. 6.47 months, HR 0.596 [95% CI 0.44, 0.81]; p=0.001).2

Indication

SARCLISA® is indicated, in combination with pomalidomide and dexamethasone, for the treatment of adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor (PI) and have demonstrated disease progression on the last therapy.

Efficacy

SARCLISA® + Pd (ICARIA-MM): Trial design

ICARIA-MM: The first positive Phase 3 trial of an anti-CD38 mAb-Pd triplet in RRMM.2

Studied in over 300 adult patients with relapsed and refractory MM in a Phase 3, multicentre, multinational, randomised, open-label, 2‑arm study.2

Adapted from Attal M et al. 2019.*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 Median time to follow-up: 11.6 months.2
sCR, CR, VGPR, and PR were evaluated by the IRC using the IMWG response criteria.2
1 patient in the SARCLISA®-Pd group was previously treated with daratumumab.2

SARCLISA® + Pd was studied in a diverse patient population.1,2

Adapted from Attal M et al. 2019 and from SARCLISA® Summary of Product Characteristics.1,2
*Information on race could not be collected in some countries, hence not all values were available.2
IgM unknown or undetected.2
Central laboratory cut-off 50% for del(17p), 30% for t(4;14) and t(14;16).2

The ICARIA-MM patient population was heavily pre-treated and also included patients with high cytogenetic risk,* patients with renal impairment, and patients who were elderly

*Central laboratory cut-off 50% for del(17p), 30% for t(4;14) and t(14;16).2
eGFR <60 mL/min per 1.73 m2.2
Aged ≥75 years.2

SARCLISA® + Pd (ICARIA-MM): Trial results

SARCLISA® + Pd extended median progression free survival by 5 months vs. Pd alone.2

Safety

SARCLISA® + Pd (ICARIA-MM): Adverse Reactions

ICARIA-MM: Adverse reactions reported in patients treated with SARCLISA® + Pd vs. Pd alone.2

Adapted from Attal M et al. 2019.2
*As reported by the investigator in the specific form of an adverse event, including infusion-related reaction, cytokine release syndrome and drug hypersensitivity.2
SARCLISA® + Pd group: one patient with myelodysplastic syndrome, one patient with post-radiation angiosarcoma and four patients with squamous cell carcinoma of the skin.2 Pd group: one patient with squamous cell carcinoma of the skin.2 All patients continued treatment after complete surgical excision except the patient with myelodysplastic syndrome.2

The most frequent serious adverse reactions are pneumonia (25.7%) and febrile neutropenia (6.6%). Patients receiving SARCLISA® should be closely monitored for signs of infection and appropriate standard therapy instituted1

At a median follow up time of 52.44 months second primary malignancies were reported in 10 IsaPd patients and 3 Pd patients1

Cases of tumour lysis syndrome (TLS) have been reported in patients who received isatuximab. Patients should be monitored closely and appropriate precautions taken.

SARCLISA® + Pd (ICARIA-MM): Haematological Abnormalities

ICARIA-MM: Haematological laboratory abnormalities in patients receiving SARCLISA® + Pd vs. Pd alone.1

The denominator used for the percentage calculation is the number of patients with at least 1 evaluation of the laboratory test during the considered observation period.1Adapted from SARCLISA® Summary of Product Characteristics.1

30.3% patients treated with SARCLISA® had neutropenic complications.1

  • Patients with neutropenia should be monitored for signs of infection
  • No dose reductions of SARCLISA® are recommended
  • SARCLISA® dose delays and the use of colony-stimulating factors (e.g. G-CSF) should be considered to mitigate the risk of neutropenia

Full blood cell counts should be monitored periodically during treatment.1

Overall discontinuation rate did not increase with addition of SARCLISA® to Pd4

SARCLISA® + Pd (ICARIA-MM): Additional safety information1

SARCLISA® + Pd (ICARIA-MM): Infusion-related reactions

ICARIA-MM: Infusion-related reactions* were mostly mild to moderate for patients receiving SARCLISA®.1

All patients who experienced infusion-related reactions, experienced them during the 1st infusion1

Infusion-related reactions were resolved on the same day in most patients, and all were reversible1

No delayed infusion-related reactions were observed and no mandatory post-infusion corticosteroid prophylaxis1,2

1/3

All patients who experienced infusion-related reactions, experienced them during the 1st infusion1

Infusion-related reactions were resolved on the same day in most patients, and all were reversible1

No delayed infusion-related reactions were observed and no mandatory post-infusion corticosteroid prophylaxis1,2

The most common symptoms of an infusion-related reaction included dyspnoea, cough, chills, and nausea. The most common severe signs and symptoms included hypertension and dyspnoea. The adverse event of severe anaphylactic reaction has been reported as a serious infusion reaction in 5 patients (0.3%) based on data from multiple clinical trials investigating isatuximab.1

In patients who experience grade 2 (moderate) infusion-related reactions, a temporary interruption in the infusion should be considered.1

*As reported by the investigator in the specific form of an adverse event, including infusion-related reaction, cytokine release syndrome, and drug hypersensitivity.2

Dosage

SARCLISA® + Pd (ICARIA-MM): Dosing and Administration

Recommended dosage1

10 mg/kg body weight administered as an IV infusion in combination with Pd*/250 mL fixed dosing volume.
Pre-medication should be administered 15 to 60 minutes prior to infusion of SARCLISA®.

*For other products administered with SARCLISA®, refer to the respective current Summary of Product Characteristics.1

Infusion rates can increase over time, with a 75-minute infusion possible from the 3rd infusion onwards*1

Adapted from SARCLISA® Summary of Product Characteristics.1

Incremental escalation of the infusion rate should be considered only in the absence of infusion-related reactions.1

  • In patients necessitating an intervention (Grade 2, moderate infusion reactions), a temporary interruption in the infusion should be considered and additional symptomatic medicinal products can be administered. After symptom improvement to grade ≤1 (mild), SARCLISA® infusion may be resumed at half of the initial infusion rate under close monitoring and supportive care, as needed. If symptoms do not recur after 30 minutes, the infusion rate may be increased to the initial rate, and then increased incrementally.
  • If symptoms do not resolve rapidly or do not improve to Grade ≤1 after interruption of SARCLISA® infusion, persist or worsen despite appropriate medicinal products, or require hospitalization or are life-threatening, treatment with SARCLISA ®should be permanently discontinued and additional supportive therapy should be administered, as needed.

*Infusion time possible in the absence of infusion-related reactions.1
 Pre-medication should be used prior to SARCLISA® infusion with the following medications to reduce the risk and severity of infusion-related reactions: dexamethasone 40 mg orally or IV (or 20 mg orally or IV for patients ≥75 years of age), paracetamol 650 mg to 1,000 mg orally (or equivalent), diphenhydramine 25 mg to 50 mg IV or oral (or equivalent [e.g. cetirizine, promethazine, dexchlorpheniramine]) (the IV route is preferred for at least the first 4 infusions).1

SARCLISA® + Pd (ICARIA-MM): Dosing Schedule

Dosing frequency decreases to Q2w in cycle 2.*1
Treatment is administered in 28-day cycles.1

  • Treatment is repeated until disease progression or unacceptable toxicity1
  • For other medicinal products that are administered with SARCLISA®, refer to the respective current Summary of Product Characteristics1
  • If a planned dose of SARCLISA® is missed, administer the dose as soon as possible and adjust the treatment schedule accordingly, maintaining the treatment interval1

*SARCLISA® dosing: 10 mg/kg body weight administered as an IV infusion in combination with Pd; fixed dosing volume of 250 mL.1
Infusion time possible in the absence of infusion-related reactions.1

MOA

SARCLISA® is an anti-CD38 mAb with a specific target epitope5,6,7

CD38 is a transmembrane glycoprotein that has multiple functions, including enzymatic and receptor-mediated activity.5,6,7

MULTIMODAL ACTIONS:2,5,7–10

In vitro, SARCLISA®

Inhibits CD38 enzymatic activity through suppression of the CD38 ectoenzyme

Triggers myeloma cell death through tumour cell targeting, including ADCC, ADCP, and CDC

Enhances immune cell function through NK cell activation and a decrease in immuno-suppressors

Directly destroys myeloma cells through apoptosis, without the need for crosslinking

SARCLISA® works synergistically with pomalidomide and dexamethasone in pre-clinical studies.5,7
References
  1. SARCLISA®. Summary of Product Characteristics. 
  2. Attal M et alLancet 2019; 394: 2096–2107.
  3. NICE. Final appraisal document. Isatuximab with pomalidomide and dexamethasone for treating relapsed and refractory multiple myeloma October 2020. Available at: www.nice.org.uk/guidance/gid-ta10448/documents/final-appraisal-determination-document [accessed: December 2023].
  4. Attal M et alLancet 2019; 394: 2096–2107. Appendix.
  5. Richardson PG et alFuture Oncol 2018;14:1035–1047.
  6. Martin TG et alCells 2019; 8(12). pii:E1522.
  7. Jiang H et alLeukemia 2016;30:399–408.
  8. van de Donk NWCJ et alBlood 2018;131:13–29. 
  9. Deckert J et alClin Cancer Res 2014;20:4574–4583. 
  10. Moreno L et alClin Cancer Res 2019;25:3176–3187.

▼This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

MAT-XU-2202578 (v3.0) Date of preparation: December 2023