ITP: Second-Line Therapy

James B. Bussel, MD:The primary second-line treatments in use in the United States, western Europe, and other parts of the world, including Japan, are a thrombopoietin receptor agonist, or a TPO receptor agonist, and rituximab-based therapy. In regard to a rituximab-based therapy, we would be particularly likely to use it, and this is my experience, though we have published data inHaematologica and theAmerican Journal of Hematologyin the past 5 years substantiating that. One person we would use it in, which is experiential and not data driven, is somebody who may be at risk for having additional autoimmune disease. For example, if there’s a patient with ITP who has a high ANA (antinuclear antibody), then that might be somebody you’d be a little more inclined to use a treatment that has a general immunosuppressive mechanism rather than one that just works on the platelets.

We believe, based on published data, that using rituximab plus 3 cycles of dexamethasone would be particularly effective if used in this woman when she’s less than 1 year from diagnosis. However, if she has already received 3 courses of prednisone, unless she’s responding very well to them, she’s likely not to want to now additionally take 3 cycles of dexamethasone. Even if she agrees to do that with the idea that she’s hoping for cure, as are all patients, it would likely be that she would hate the first cycle of dexamethasone so much that she might not want to persist. Whether other treatments could be substituted for dexamethasone is a subject of ongoing investigation. The idea of combining dexamethasone with rituximab is to attack the plasma cells as well as the B cells, which rituximab attacks.

Transcript edited for clarity.

Case: A 44-year-old woman presenting with reddish-purple rash on lower legs

February 2017

• Patient presents with complaints of a reddish-purple rash on her lower legs and “constant” bruises appearing “spontaneously” without her remembering any trauma
• Physical evaluation reveals:
  • The rash to be petechiae (subcutaneous bleeding)
  • Slightly overweight (BMI = 26.5 kg/m²)
  • Patient is afebrile, with no splenomegaly
• When asked, reports her menstrual flow is unusually heavy, but says she was evaluated for and had no evidence of fibroids or endometriosis
• No personal or family history of cancer; no recent viral illnesses; no bone pain
• Current medications: no chronic medications; acetaminophen as needed; multivitamin
• Laboratory findings:
  • CBC reveals platelets 21 X 10⁹/L
  • All other findings with normal range
  • Negative forH pylori, HIV, and HCV
• Diagnosis: chronic ITP
  • Started course of prednisone 1 mg/kg X 21 days, then tapered off; at evaluation, platelets: 27 X 10⁹/L
  • Second course of prednisone 1 mg/kg X 21 days; at evaluation, platelets still <30
  • Third course of prednisone 1 mg/kg X 21 days; at evaluation, platelets still <30

February 2018

• &ldquo;Rash&rdquo; partly resolved, bruising still present
• Patient complains of weight gain on treatment and trouble sleeping
• After discussion with patient, she is started on eltrombopag (PROMACTA), at a dose of 50 mg/day