Page 22 - Haematologica Vol. 107 - September 2022

REVIEW ARTICLE - ITP: diagnosis and second-line treatment J.B. Bussel and C.A. Garcia Table 1. Comparing second-line treatment options in non-pregnant premenopausal females.
Treatment options
Pros
Cons
Rituximab
High likelihood of good response in both short and especially long term (>50%)
Risk of first-infusion reaction which can be mitigated by steroids COVID vaccination not possible for 6-12 months
Very rare risk of PML45
Risk of hypogammaglobulinemia with rituximab + dexamethasone 10-20% with possible need for short-term IgG-replacement IVIG
TPO-RA: Eltrombopag Romiplostim Avatrombopag
Very high response rate (70-80%)
Risk of thrombosis (increased with OCP, underlying APLA, other prothrombotic causes) which usually occurs in 1st year of use
Pain from headache-myalgia may occur
Abnormal liver function, especially for eltrombopag which also needs very strict ingestion on empty stomach
Splenectomy
High long-term response rate (60-70%)
Risk of perioperative bleeding, VTE, intracellular infection, sepsis Need to vaccinate at least 15 days prior to surgery88 Revaccination schedule unknown
Fostamatinib
Overall response 43% in first 12 weeks on treatment, time to re- sponse 15 days47
Side effects: hypertension, nausea-diarrhea, dizziness, ALT increases
Clinically meaningful responses in patients with failure of splenec- tomy, TPO-RA and/or rituximab45
Immunomodulatory agents: azathioprine, mycophenolate mofe- til, cyclosporine, dap- sone, cytoxan
Many years of usage in some cases e.g., azathioprine,
Attacks pathophysiology of autoim- mune disease
Usually slow responses, which can take 1-3 months to develop without predictability
Various individual toxicities:
Cyclosporine - neurological and renal Azathioprine and danazol – liver abnormalities Danazol - facial hair and acne MMF-headache, gastrointestinal
Dapsone - hemolysis
COVID: coronavirus disease 2019; PML: progressive multifocal leukoencephalopathy; IVIG: intravenous immunoglobulin; TPO-RA: thrombopoietin receptor agonist; OCP: oral contraceptive pills; APLA: anti-phospholipid antibody; VTE: venous thromboembolism; ALT: alanine aminotransferase; MMF: mycophenolate mofetil.
termined the optimal dose, 375 mg/m2 once a week for 4 weeks is the most commonly used dosing regiman. The addition of dexamethasone to the rituximab may provide an extra “curative” effect via the former’s anti-plasma cell effect, although it also increases the risk of hypogamma- globulinemia. Administration of dexamethasone would re- duce the first-infusion side effects of rituximab, and our patient could stop the steroid after one or two cycles if she does not tolerate it well instead of completing three cycles.
It is prudent to check immunoglobulin levels to rule out CVID and a hepatitis B panel prior to starting rituximab. The risk of coronavirus disease 2019 (COVID) and delayed vaccination are in addition to other potential side effects such as first-infusion reactions, serum sickness, and even the very rare possibility of progressive multifocal leuko- encephalopathy. If dexamethasone and rituximab are combined, there is a 10-20% possibility of developing hy- pogammaglobulinemia which may necessitate IVIG for a few months even in patients who start out with normal immunoglobulin levels. Combining this problem with the
issue of the patient being unable to undergo vaccination for COVID reduces the benefit/risk ratio of rituximab treat- ment substantially, despite its curative potential. If the coronavirus pandemic wanes, this may be less of a con- sideration.
If treatment with rituximab is delayed too long in this woman, the chance of “cure” may be reduced. Her immu- noglobulin levels are normal and she does not have hepa- titis B surface antigen, so the risks of aggravated hepatitis B and hypogammaglobulinemia are less substantial. Luc- chini et al. provide more information on the place of ri- tuximab treatment in ITP.27
Whether because of vaccination and/or infection, the cur- rent COVID pandemic is affecting ITP management and may have an impact on patients who are on second-line ITP treatment options. Guidelines on post-infection or vaccination ITP treatment are summarized in Table 2. Our patient should be vaccinated against SARS-CoV-2 at least 5-8 weeks before initiating rituximab in order to have time to receive and fully respond to both doses of Moderna and Pfizer vaccines. It might be optimal to wait a little longer
Haematologica | 107 September 2022
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