What is the treatment plan for a patient with Immune Thrombocytopenic Purpura (ITP) who has had an insufficient response to corticosteroids or immunoglobulins, considering romiplostim (Nplate) as a treatment option?

Romiplostim for ITP After Corticosteroid/Immunoglobulin Failure

For adults with ITP lasting ≥3 months who have failed or are dependent on corticosteroids/immunoglobulins, romiplostim is a preferred second-line treatment option, with the American Society of Hematology recommending TPO-receptor agonists (including romiplostim) over rituximab and suggesting either TPO-RAs or splenectomy as appropriate choices. 1

Patient Selection and Timing

Initiate romiplostim in adults with ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy, particularly when the degree of thrombocytopenia and clinical condition increases the risk for bleeding. 2

• Do not delay switching to second-line therapy like romiplostim in patients requiring on-demand corticosteroid administration after completing first-line induction 3
• Avoid continuing initial corticosteroid treatment beyond 6-8 weeks before considering romiplostim to prevent prolonged corticosteroid exposure 3
• The 2024 ASH guideline review confirmed that TPO-RAs (including romiplostim, eltrombopag, avatrombopag, and hetrombopag) remain appropriate for adults with persistent and chronic ITP lasting ≥3 months who are corticosteroid-dependent or non-responsive 1

Positioning in Treatment Algorithm

TPO-receptor agonists like romiplostim are preferred over rituximab for second-line therapy, while the choice between TPO-RAs and splenectomy should be based on patient-specific factors. 1

Key Treatment Hierarchy:

• TPO-RA vs Rituximab: ASH guidelines suggest TPO-RAs rather than rituximab (conditional recommendation) 1
• TPO-RA vs Splenectomy: Either option is acceptable; the choice depends on individual circumstances 1
• Rituximab vs Splenectomy: Rituximab is suggested over splenectomy (conditional recommendation) 1

Decision-Making Factors:

• Patients wishing to avoid surgery should choose romiplostim or rituximab over splenectomy 1
• Patients valuing avoidance of long-term medication may prefer splenectomy or rituximab 1
• Patients prioritizing durable response may prefer splenectomy or TPO-RAs like romiplostim 1
• Splenectomy should ideally be delayed for at least 1 year after diagnosis due to potential for spontaneous remission 1
• TPO-RAs demonstrate 70-80% response rates in clinical trials, while splenectomy has 20-30% relapse rates and requires lifelong sepsis prevention management 3

Dosing and Administration

Start romiplostim at 1 mcg/kg actual body weight administered subcutaneously once weekly, with dose adjustments based on platelet response. 2

Dose Titration Protocol:

• Target platelet count: ≥50 × 10⁹/L to reduce bleeding risk (do not attempt to normalize counts) 2
• If platelet count <50 × 10⁹/L: Increase dose by 1 mcg/kg weekly 2
• If platelet count >200 × 10⁹/L and ≤400 × 10⁹/L for 2 consecutive weeks: Reduce dose by 1 mcg/kg 2
• If platelet count >400 × 10⁹/L: Withhold dose, assess weekly, resume at reduced dose (1 mcg/kg lower) when count falls <200 × 10⁹/L 2
• Maximum weekly dose: 10 mcg/kg 2
• Most adult patients who respond achieve and maintain target counts with a median dose of 2-3 mcg/kg 2

Monitoring Requirements:

• Obtain complete blood counts with platelet counts weekly during dose adjustment phase 2
• After establishing stable dose, monitor monthly 2
• Following discontinuation, obtain CBCs weekly for at least 2 weeks 2

Expected Efficacy

Romiplostim produces durable platelet responses in approximately 38-61% of patients, with overall response rates (durable plus transient) of 83%. 4, 5

• In controlled trials, 61% of non-splenectomized patients and 38% of splenectomized patients achieved durable platelet response (≥50 × 10⁹/L for ≥6 of last 8 weeks) 4, 5
• Response typically occurs within a median of 14 days after 1-5 infusions 6
• Long-term data demonstrates maintained efficacy with stable dosing for up to 5 years, with 95% of patients achieving platelet response at least once 7
• Approximately 30% of patients achieve long-term (≥6 months) treatment-free remission after discontinuation, compared to only 9% spontaneous remission in untreated adults 3

Safety Considerations and Monitoring

Major Safety Concerns:

• Bone marrow reticulin formation: Increased reticulin was found in 10 or more patients in romiplostim trials 1, 4
• Worsened thrombocytopenia after discontinuation: Monitor closely for rebound thrombocytopenia 4
• Thrombotic/thromboembolic complications: May result from platelet count increases; thrombotic events occurred in 6.5% of patients but were not associated with platelet count 2, 7
• Portal vein thrombosis: Reported in patients with chronic liver disease 2

Common Adverse Events:

• Most frequent: headache (37%), nasopharyngitis (32%), contusion (30%), epistaxis (30%), fatigue (30%), arthralgia (25%), diarrhea (25%) 5
• Treatment-related serious adverse events were infrequent and did not increase with longer treatment duration 7

Critical Pitfall to Avoid:

Discontinue romiplostim if platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the maximum weekly dose of 10 mcg/kg. 2

Romiplostim vs Eltrombopag

Either romiplostim or eltrombopag is acceptable, with choice primarily driven by patient preference for route of administration (weekly subcutaneous injection vs daily oral medication). 1

• No substantial differences in efficacy or safety between the two TPO-RAs 1
• Romiplostim: weekly subcutaneous injection, generally self-administered at home 7
• Eltrombopag: daily oral medication with dietary restrictions for food and polyvalent cations (calcium) that may affect adherence 1
• Both agents are well-tolerated with long-term use and show similar efficacy profiles 3

Contraindications and Limitations

Romiplostim is not indicated for thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause other than ITP. 2

• In some MDS patients, romiplostim increases blast cell counts and increases risk of progression to acute myelogenous leukemia 2
• Use only in ITP patients whose degree of thrombocytopenia and clinical condition increases bleeding risk 2
• Should not be used to normalize platelet counts 2