Page 31 - Haematologica Vol. 107 - September 2022

REVIEW ARTICLE - ITP: diagnosis and second-line treatment J.B. Bussel and C.A. Garcia
cytopenia is drug-induced. Diagnosis generally relies on recognizing medications likely to cause thrombocytopenia; one approach is to change medications if any are newly initiated. Viral infections could also occur in this population e.g., hepatitis C, cytomegalovirus.
Patients over the age of 60 are thought to have a higher likelihood of fatal and non-fatal serious bleeding compared to younger patients;77-79 recent studies of intracranial hemorrhage have supported earlier findings demonstrating a higher risk in those above 60 years of age. Thus, it may be appropriate to pursue an aggressive approach in this pa- tient, such as the addition of IVIG to steroids.
Which second-line treatment is optimal for
a 63-year-old male?
Rituximab in an older male
In this case of ITP, the older man has a reasonable likeli- hood of a response but, even if he responds well, his re- sponse will very likely last only 6-12 months. The chance of a long-term (>1 year) response is low. Furthermore, as dis- cussed previously, after rituximab it would not be possible to vaccinate the patient against SARS-CoV-2, which is im- portant since this 63-year-old is in a high-risk group and would benefit from boosters. As indicated, there is a 10- 20% possibility of developing significant hypogammaglob- ulinemia when the combination of dexamethasone with rituximab is used.26 A good initial response followed by the expected relapse would allow rituximab to be reused, but it remains unlikely to lead to a cure80 and the probability of hypogammaglobulinemia occurring is thought to increase with repeated use.
Splenectomy in an older male
Splenectomy is used even less in this age group, since ef- ficacy is lower, and the risk of side effects is higher. The re- sults of splenectomy are less successful in older patients with ITP, but there is no clear age at which this effect oc- curs.81 In addition, there may be a higher risk of peri-oper- ative complications and post-splenectomy thrombosis in this older patient. One could take a risk-based approach to splenectomy for this 63-year-old by considering the co- morbidities and proceeding if he has few to no comorbid- ities.
Thrombopoietin receptor agonists in an older male
Another second-line therapy is a TPO-RA. The primary ad- vantages remain the high response rate and the low likeli- hood that there will be major side effects although venous and arterial thrombosis would be the primary concerns in this older man. It is important to fully assess the risk of thrombosis looking at risk factors such as obesity, family history, and personal history.53 The use of thrombopoietin agents would be similar in both patients and is described in the package inserts and a recent review.36
If romiplostim is chosen, we would initiate treatment with 3 mg/kg/week and increase by 2 mg/kg/week until the pla- telet count rises above 30-50x109/L. In more practical terms, this could mean whole vials of 250 and 500 micro- grams which are almost universally available; if smaller and larger vial sizes are/become available this would allow more precise weight-based dosing. If a sufficient platelet count isachieved,itisimportantnottochangeromiplostimdoses too quickly, i.e., not more than 1 mg/kg/week. This minimizes cycling of platelet counts and prevents them from going too high or falling too low. If the platelet count goes very high (with any of the 3 TPO-RA), do not withhold the dose, but decrease it by 1 mg/kg (or equivalent); several days of aspirin can be given if there is concern of thrombosis.
If eltrombopag is chosen, the starting dose is 50 mg by mouth daily; lower doses might be required in East Asian patients. If the count does not increase sufficiently within 1-2 weeks, increase the dose to 75 mg daily. If the count increases too much, decrease the dose to 25 mg daily. The maximum change would be 25 mg/daily once a week. If none of the doses allows for a stable count of 50-100x109/L, then alternating doses might be preferred e.g., 50 mg on odd days and 75 mg on even days. As discussed, eltrombo- pag must be taken on an empty stomach. In our experi- ence, the best approach is to eat dinner, not eat after the end of dinner and then take the eltrombopag with water at bedtime, at least 2 hours after dinner. If this gentleman uri- nates every night, this could be a time to take eltrombopag. If avatrombopag is chosen, the starting dose is 20 mg daily. The dose could be adjusted to as high as 40 mg daily or as low as 20 mg on one day per week. There is only one size of avatrombopag tablet, i.e. 20 mg. The tablet is taken once daily and there are no dietary restrictions. As with the other agents, dose changes should be limited in magnitude and not performed more often than weekly.
With all three agents, it is not clear how/when to taper and attempt to discontinue treatment. A recent study demonstrated a greater than 50% successful discontinu- ation rate when at least 2-3 months of stable TPO-RA dosing, no bleeding, and a platelet count >100x109/L were required for the discontinuation attempt.82 Patients were on romiplostim a median of 12 months before tapering; the doses administered were higher than normal to obtain stable counts >100x109/L. The tapering protocol was at 2- weekly intervals for a total of not more than 2 months of tapering. It remains unclear how often a patient who has required a thrombopoietin agent for 2 or more years will be able to discontinue treatment. Other studies have sug- gested an approximately 20-25% rate of successful dis- continuation in the first year.
Fostamatinib in an older male
If this patient were at particular risk of thrombosis, fosta- matinib might be a particularly good option. Otherwise, in
Haematologica | 107 September 2022
2030