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Immune thrombocytopenia (ITP) can be associated with lymphoproliferative diseases (LPD) or solid tumors. A systematic review of published literature was conducted to evaluate response to treatment of ITP secondary to malignancy. Primary outcome was overall response (complete response+response) to first-line treatments [steroids alone or in combination with intravenous immunoglobulins (IVIg)]. Among secondary outcomes, overall response to second-line treatments [splenectomy, rituximab or thrombopoietin receptor agonists (TPO-RA)] and death were evaluated. Of the retrieved 238 text articles, 108 were analyzable, for a total of 154 patients: 142 in 105 case reports and 12 in 3 observational studies. Thirty-nine patients had solid tumors, 114 LPD, and 1 both. The median follow up was 19 months (IQR, 9–40). The overall response was 50% (62% in solid tumors, 46% in LPD) after steroids and 47% (67% in solid tumors, 36% in LPD) after steroids+IVIg, which are lower than historical responses observed in primary ITP (≈80%). The overall responses to rituximab (used in LPD only), splenectomy and TPO-RA (70%, 73% and 92%, respectively) were similar to those observed in primary ITP. Seven patients (6%) died due to bleeding events. ITP secondary to malignancy appears to be associated with unsatisfactory response to first-line treatments.

Previous meta-analyses reported discordant results on the efficacy and safety of thrombopoietin receptor agonists (TPO-RA) as second-line treatment in patients with immune thrombocytopenia (ITP). We conducted a meta-analysis of primary ITP treatment with the TPO-RA Romiplostim, Eltrombopag and Avatrombopag, including additional studies and relevant endpoints. We searched MEDLINE, EMBASE and CENTRAL for randomized clinical trials (RCTs) and cohort studies on TPO-RA in ITP published until December 31, 2018. The primary endpoints were: risk ratio (RR) of treatment failure and bleeding of WHO grade ≥2; rate of remission after discontinuation of treatment. The principal safety outcome was RR and incidence of thrombotic events and liver damage. From 1044 identified records we selected 16 RCTs and 19 cohort studies. RCTs included 909 patients assigned to TPO-RA and 427 to the control arm. Treatment failure was observed in 21% TPO-RA-treated patients and 47% control arm patients (RR = 0.42, 95% CI 0.33–0.53) in RCTs during a median follow-up of 13 weeks, and in 29% TPO-RA-treated patients in cohort studies, during a median follow-up of 69 weeks. The incidence of remission after TPO discontinuation was 18% (5–36%). RR of WHO grade ≥2 bleeding was 0.58 (0.38–0.86) in TPO-RA-treated patients, compared to control arm patients. Adverse events were rare and not significantly different in the two groups of patients. All-cause mortality was significantly lower with TPO-RA (RR 0.21, 95% CI, 0.06–0.68). In conclusion, TPO-RA are effective and safe in patients with ITP, even in the long term.