Why are Mavenclad (cladribine) or hematopoietic stem cell transplant considered next options for a patient with multiple sclerosis (MS) showing radiographic evidence of disease progression while on Ocrevus (ocrelizumab)?

Mavenclad or Hematopoietic Stem Cell Transplant for MS with Disease Progression on Ocrevus

For patients with MS showing radiographic evidence of disease progression while on Ocrevus (ocrelizumab), Mavenclad (cladribine) or hematopoietic stem cell transplantation (HSCT) are considered next-line options because they offer alternative mechanisms of action with potential to halt disease progression when high-efficacy B-cell therapy has failed.

Why These Options Are Considered Next

Treatment Failure on Ocrevus

• Ocrevus (ocrelizumab) is a humanized anti-CD20 monoclonal antibody that depletes B cells and is FDA-approved for both relapsing MS and primary progressive MS 1, 2
• Despite its efficacy in reducing relapse rates by 61% compared to interferon beta-1a and slowing disability progression 2, some patients still show radiographic evidence of disease progression
• When a high-efficacy therapy like Ocrevus fails, treatment escalation to therapies with different mechanisms of action is warranted

Mavenclad (Cladribine) as Next Option

• Mavenclad is a deoxyadenosine analogue prodrug that preferentially depletes lymphocytes through a different mechanism than Ocrevus 3
• Key advantages of Mavenclad:
  • Short-course oral administration (two short courses 1 year apart) offering convenience with low treatment burden 3
  • Demonstrated efficacy in highly active relapsing MS with reduction in:
    • Clinical relapse
    • Disability progression
    • MRI-assessed disease activity 3
  • Real-world data shows 87.5% reduction in annual relapse rate in treatment-naïve patients with highly active MS 4
  • May be particularly effective in patients with high disease activity (HDA) 3

Hematopoietic Stem Cell Transplantation (HSCT) as Next Option

• HSCT offers a more intensive approach for aggressive, treatment-refractory MS 5
• According to ECTRIMS and EBMT guidelines, HSCT can be considered for:
  • Patients who have failed ≥1 high-efficacy disease-modifying therapy (like Ocrevus) with poor prognostic factors 6
  • Patients with increasing EDSS scores despite treatment 6
  • Young (<45 years) individuals with early disease and evidence of inflammatory activity 6, 5
• HSCT has shown impressive long-term outcomes:
  • Progression-free survival of 87% at 10 years in relapsing-remitting MS 6
  • Potential for sustained complete remission of MS 6

Decision Algorithm for Choosing Between Options

Consider Mavenclad when:

1. Patient prefers oral administration with minimal treatment burden
2. Patient has contraindications to intensive procedures
3. Disease progression is present but not aggressive/rapid
4. Patient has concerns about fertility (temporary impact vs. HSCT)
5. Comorbidities make HSCT higher risk

Consider HSCT when:

1. Patient has failed multiple high-efficacy DMTs including Ocrevus
2. Disease is highly aggressive with poor prognostic factors
3. Patient is younger (<45 years) with shorter disease duration
4. Evidence of significant inflammatory activity on MRI
5. Patient has excellent performance status with no major comorbidities
6. Patient understands and accepts transplant-related risks

Important Caveats and Considerations

• HSCT is not recommended for:

  • Patients with EDSS >6.0 or disease duration >20 years 5
  • Progressive MS without detectable inflammatory lesion activity 6
  • Long-standing, advanced MS with severe disability 6
  • Patients with multiple medical comorbidities 6

• Mavenclad considerations:

  • Acceptable tolerability profile without increased risk of overall infection 3
  • No apparent increased risk of malignancy versus matched reference populations 3
  • Requires monitoring but less intensive than HSCT

• Treatment decisions should factor in:

  • Pattern and rate of disease progression
  • Age and overall health status
  • Prior treatment response
  • Patient preferences regarding risk tolerance and treatment burden
  • Access to specialized HSCT centers with MS expertise

By carefully evaluating these factors, the most appropriate next treatment option can be selected to maximize the chance of halting disease progression and preserving neurological function.