What are the bleeding rates with Kisqali (ribociclib) and Leqembi (lecanemab)?

Bleeding Rates with Kisqali (Ribociclib) and Leqembi (Lecanemab)

Leqembi (lecanemab) is associated with significantly higher bleeding risks, particularly amyloid-related imaging abnormalities with hemorrhage (ARIA-H) in 17.3% of patients and intracerebral hemorrhage in 0.7% of patients, while Kisqali (ribociclib) has minimal bleeding risks with no specific hemorrhagic safety concerns in its profile.

Leqembi (Lecanemab) Bleeding Risks

Leqembi is associated with several types of bleeding risks:

ARIA-Related Bleeding

• 17.3% of patients treated with Leqembi experienced ARIA-H (amyloid-related imaging abnormalities with hemorrhage) compared to 9.0% on placebo 1
• Intracerebral hemorrhage >1 cm in diameter occurred in 0.7% of Leqembi patients versus 0.1% on placebo 1
• Fatal events of intracerebral hemorrhage have been observed in patients taking Leqembi 1

Risk Factors for ARIA and Bleeding with Leqembi

1. ApoE ε4 Carrier Status:

   • ApoE ε4 homozygotes: 45% ARIA risk (vs 22% on placebo)
   • ApoE ε4 heterozygotes: 19% ARIA risk (vs 9% on placebo)
   • Non-carriers: 13% ARIA risk (vs 4% on placebo) 1

2. Radiographic Findings of Cerebral Amyloid Angiopathy (CAA):

   • Baseline presence of ≥2 microhemorrhages or ≥1 area of superficial siderosis increases ARIA risk 1
   • Prior cerebral hemorrhage >1 cm in diameter increases risk 1

3. Concomitant Antithrombotic Medications:

   • Intracerebral hemorrhage occurred in 0.9% of patients taking Leqembi with concomitant antithrombotic medication versus 0.6% without 1
   • Higher risk (2.5%) when combining Leqembi with anticoagulants alone or with antiplatelet medications 1
   • Fatal cerebral hemorrhage has occurred with anti-amyloid antibodies when combined with thrombolytic agents 1

Severity and Monitoring

• The radiographic severity of ARIA-H with Leqembi was:
  • Mild in 9% of patients
  • Moderate in 2% of patients
  • Severe in 3% of patients 1
• Superficial siderosis was mild in 4%, moderate in 1%, and severe in 0.4% 1

Kisqali (Ribociclib) Bleeding Profile

Kisqali has no specific bleeding risks highlighted in its safety profile:

• The most common adverse reactions (≥20%) include:

  • Leukocytes decreased
  • Neutrophils decreased
  • Hemoglobin decreased
  • Lymphocytes decreased
  • Various liver enzyme elevations
  • Nausea, arthralgia, and alopecia 2

• Thrombocytopenia occurs in 9% of patients but is not associated with significant bleeding events 2

• No specific hemorrhagic events are listed among the common or serious adverse reactions 2

• Kisqali is primarily eliminated through hepatic metabolism (84%), with minimal renal excretion (7%), intestinal excretion (8%), and biliary elimination (1%) 3

Clinical Implications and Management

For Leqembi:

1. Mandatory ApoE ε4 Testing:

   • Testing for ApoE ε4 status should be performed prior to initiating Leqembi to identify patients at higher risk of ARIA 1

2. MRI Monitoring:

   • Regular MRI monitoring is essential for patients on Leqembi
   • Most ARIA-E events occur within the first 7 doses but can occur at any time 1

3. Caution with Antithrombotics:

   • Exercise extreme caution when considering Leqembi in patients requiring anticoagulation 1
   • Avoid thrombolytic agents in patients with focal neurologic symptoms who are on Leqembi without first ruling out ARIA-E 1

For Kisqali:

1. Routine Monitoring:
   • Regular monitoring of complete blood counts is recommended, primarily for neutropenia rather than bleeding risk 2
   • No specific bleeding precautions are needed

Comparative Risk Assessment

The bleeding risk profiles of these two medications differ substantially:

• Leqembi carries significant bleeding risks, particularly intracerebral hemorrhage and ARIA-H, with specific risk factors and monitoring requirements
• Kisqali has no specific bleeding risks identified in clinical trials or its FDA label

When considering these medications, clinicians should be particularly vigilant about bleeding risks with Leqembi, especially in patients with risk factors such as ApoE ε4 homozygosity, concomitant anticoagulant use, or radiographic evidence of cerebral amyloid angiopathy.