Written in Blood
• 7 had an associated malignant hematologic disorder
• 1 had a primary immunodeficiency
Most patients achieved a transient initial response to
first-line steroid therapy (n=24; 68.6%) and IVIg (n=22;
68.6%), before becoming refractory to treatment.
Median follow-up for patients with multirefractory
ITP was 84 months (range = 12-455 months) and 48
months (range = 12-369 months) for ITP controls. In the
control population, the researchers found that the following characteristics were associated with a higher risk of
developing multirefractory ITP during follow-up:
• Bleeding symptoms at ITP onset (odds ratio [OR] =
3.54; 95% CI 1.12-11.22; p=0.032)
• No response to steroid therapy (OR=0.38; 95% CI
0.20-0.72; p=0.003)
Patients with multirefractory ITP were more likely to
have secondary ITP (OR=4.84; 95% CI 1.31-17.86;
p=0.018) and MGUS (OR=5.94; 95% CI 1.08-32.48;
p=0.04). “This overrepresentation, and poor response to
steroid therapy, suggest that the immunologic mechanism
resulting in platelet destruction in these cases differs from
the common form of ITP,” the authors wrote.
The median duration of ITP prior to multirefractory
transition was 78 months (range = 6-450 months), and
patients had received a median of 10.5 treatments for
ITP (range = 6-15 treatments). Almost all of the multirefractory ITP patients (n=34; 91.8%) did not achieve a
prolonged response to rituximab, splenectomy, and the
two Tpo-RAs at the maximum tolerated dose.
At the end of follow-up for the multirefractory population, only 30 percent (n=11) had achieved a sustained
response.
Seven patients had a malignant hematologic disorder
– three of whom achieved a sustained response with chemotherapy, one with smoldering myeloma who received
lenalidomide then Tpo-RAs with no efficacy, and three
who received no specific treatment other than rituximab.
Among the 30 patients with no hematologic malignant disorder, 14 received at least one immunosuppressant or cytotoxic agent, but only one patient achieved a
response. Ten patients received an immunosuppressant
along with Tpo-RA; seven of these patients achieved
a sustained response during a median follow-up of 15
months (range = 6-32 months).
“ITP can precede the diagnosis of a malignant hematologic disorder, which suggests that, with multirefractory
ITP, the diagnosis of primary ITP should be reconsidered
to carefully exclude hematologic disorders,” the authors
wrote. Based o n their findings, they suggest that multirefractory ITP can be divided into three categories:
• Primary ITP
• ITP associated with other autoimmune disorders
Five patients (14%) in the study died due to intracranial
hemorrhage (n=2), sepsis (n=1), breast cancer (n=1), and
unknown reasons (n=1). All patients required several
hospitalizations (median = 15; range = 6-100). Forty percent (n=15) presented with at least one bacterial infection
and 24 percent (n=9) experienced thrombosis.
“Uncontrolled bleeding and therapy-related complications were the two most challenging problems: 60 percent
of patients needed platelet transfusion during follow-up,
and 40 percent had at least one severe infection,” the
authors added.
“In the era of new ITP therapies, a minority of ITP
patients still does not show response after several treatment lines and likely have severe disease, with high
morbidity and risk of death,” Dr. Mahévas and colleagues
concluded. “In the absence of guidelines, an individual
approach with a combination of agents taking into account the risk/benefit balance of these treatments appears
the best way to improve the outcome of patients with
multirefractory ITP.”
The study is limited by its retrospective design, as well
as the wide variety of previous therapies that patients had
received since this variance may have affected the interpretation of study outcomes. ●
REFERENCE
• ITP associated with other malignant hematologic
disorders
Mahévas M, Gerfaud-Valentin M, Moulis G, et al. Characteristics, outcome and response to therapy
of multirefractory chronic immune thrombocytopenia. Blood. 2016 June 27. [Epub ahead of print]
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ASH Clinical News
September 2016