Second-Line Therapy and Beyond for ITP

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 inHaematologicaand 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.

The other setting where rituximab in combination with dexamethasone is particularly useful, in our opinion, is when you have a woman with ITP who has had it for less than 1 year. Our data suggest that giving standard-dose rituximab and 4 cycles of dexamethasone in such a patient will result in cure perhaps 70% or more of the time. Whereas men with short duration or long duration of disease and women with duration of disease longer than 1 year do not do nearly as well, and the long-term cure rate is only 10% to 20%, which may reflect spontaneous improvement over time. We would use a rituximab-based therapy in a patient with apparent autoimmune disease or in a woman with ITP that’s still persistent, ie, of less than 1 year’s duration.

TPO-RAs would potentially be used in other patients when you’re going to second-line therapy. Most patients would prefer to take a pill once a day, such as eltrombopag, as opposed to getting a shot once a week. However, taking a pill once a day requires adjusting one’s diet and schedule around that to some extent and potentially altering eating habits. So, that can be difficult for some people and has been a reason in our practice why certain patients don’t seem to respond to it.

Currently, in Europe but not the United States, the patient is allowed to learn to give themselves their own shot of romiplostim at home, and therefore, that makes it an easier therapy to use with training, given that it’s a little bit hard to measure the dose exactly. And since you’re only doing the injection once a week, it’s actually not often enough to really keep somebody in good practice. However, to be fair, in clinical trials, the great majority of patients attempting to use home care with romiplostim have been able to do it without any significant degree of problems. And it’s likely—though we don’t know this for a fact—based on publications, for example, from Jim George 2 years ago in aCommunity Supportive Oncologyjournal, that eventually, in the United States, romiplostim will be licensed for home care. Having said all of that, the choice between the 2 is largely based on that and that if the patient’s insurance will cover eltrombopag, or Promacta, and the patient is able and willing to adjust their diet—which may just mean not eating after dinner and being able to take a medication 2 hours or more after dinner is finished—then that’s not a very difficult thing to do.

Transcript edited for clarity.

Case: A 48-year-old woman presenting with unusual bruising

October 2017

• A 48-year-old woman presents with complaints of bruising after minor bumps, bleeding gums despite regular tooth cleaning, and a recent spontaneous bloody nose; symptom onset about 1 year ago
• Physical evaluation reveals a woman of normal weight and average height, afebrile, no splenomegaly
• No personal or family history of cancer, autoimmune disease; no recent viral illnesses; no bone pain or night sweats
• Current medications: ibuprofen as needed, generic hydrochlorothiazide (HCTZ)
• Laboratory findings:
  • CBC reveals platelets 28 X 10⁹/L
  • WBCs within normal
  • Renal and hepatic function within normal
• Diagnosis: idiopathic thrombocytopenic purpura
• Patient started on a course of prednisone 1 mg/kg for 21 days, then tapered off
  • Platelets: 29 X 10⁹/L
  • Second course of prednisone 1 mg/kg for 21 days

April 2018

• After 2 courses of prednisone, patient’s platelets have not recovered
  • CBC shows platelets at 28 X 10⁹/L
• Symptoms of easy bruising and bleeding from gums continue
• After discussion with patient, she is started on the thrombopoietin receptor agonist (TPO-RA) eltrombopag (PROMACTA), at a dose of 50 mg/day
  • Dose increased to 75 mg/day; last platelet count, 65 X 10⁹/L