EHA 2023 – Report: treatments

EHA 2023 – Report: treatments
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Among the abstracts presented at the 2023 EHA meeting, many focused on new drugs.  In particular the FcRn inhibitor efgartigimod and the BTK inhibitors showed promising results, but also real-life experiences with fostamatinib, the TPO-mimetics and a meta-analysis on rituximab were presented.

Results of the ADVANCE+ study, a 52-week open-label extension (OLE) of the phase III, randomized, placebo-controlled trial with intravenous efgartigimod (the neonatal Fc receptor inhibitor) have been presented. 101 patients enrolled in the ADVANCE study entered the OLE and at the time of data analysis, 26.7% have completed the 52-week period, while 45.5% are still on treatment and 50% discontinued the study, 45% of them (23/51) due to lack of efficacy. Despite sustained reduction of 60% from baseline in total serum IgG levels, infections occurred in 33.7% of patients, mostly mild. The mean percentage of weeks with platelet count ≥50×109/L was 39.2% (Carpenedo M. et al.).

Orelabrutinib, an irreversible BTK inhibitor, is being tested as second-line therapy in a phase II trial in China, where patients are randomized to receive 50 mg/day (n=15 patients) or 30 mg/day (n=18 patients), with a permitted intra-patient dose-escalation in case of nonresponse. Overall, 12/33 patients (36.4%) experienced an increase in platelet count ≥50×109/L in the first 4 weeks of treatment. Responses were higher in the 50mg arm (40%) compared with the 30mg arm (22%), in which 12 patients needed to increase the dose. 27% achieved a durable response (platelet count ≥50×109/L for at least 4/6 visits). Adverse events were all grade 1-2 (Shi Y et al.).

Another BTK-inhibitor, zanubrutinib, has been administered in a phase I trial for a fixed-duration treatment of 6 weeks in 40 adult ITP patients resistant or relapsed after corticosteroid treatment. 22 patients (55%) achieved an overall response (platelet count ≥30×109/L). Notably, 6/22 were receiving a concomitant, non-corticosteroid treatment. The most common reported adverse events were infections, generally mild (Huang QS et al.).

The real-world use of fostamatinib has been explored by the French group within the CARMEN-ITP registry. 61 fostamatinib-treated patients from October 2021 to October 2022 were included, most of them with heavily pretreated, refractory ITP (5 median number of previous lines, median ITP duration 6.5 years). Response rate to fostamatinib was 30%, with a median duration of treatment of 2.2 months. 10 patients interrupted treatment due to inefficacy, 12 due to adverse drug reactions (Moulis G. et al.). The Spanish group has instead examined patients that, after having achieved a complete response, could taper and discontinue fostamatinib in the Spanish Fostasur observational, retrospective study. 44 patients were included, and the drug was successfully discontinued in 5 (11%). After a median follow-up of 11 weeks, only one patient relapsed, and responded again to fostamatinib resumption (Mingot-Castellano M.E. et al.).

The JAK1-2 kinase inhibitor baricitinib seems to inhibit IFN-induced antigen presentation: on these grounds a phase 2 trial with baricitinib fixed-duration (6 months) second-line therapy in adult patients with ITP is ongoing in China. 28 patients were treated, durable response (at 6 months) was achieved in 20 patients (71%), with a median time to response of 13 days. Nearly 50% of patients taking concomitant medications at baseline (steroids and TPO-mimetics) were able to discontinue the drugs (Zhao P. et al.).

A Chinese group also assessed the efficacy of a romiplostim biosimilar, QL0911 versus placebo in a randomized phase III trial of ITP adult patients who failed first-line therapy. Durable responses were achieved in 62% of patients treated with QL0911, significantly higher than the placebo group (as expected). No comparison with romiplostim was made (Zhou H. et al). A real-world study of hertrombopag, a TPO-mimetic made in China, showed that among 50 ITP patients with R/R ITP who started treatment, 46% responded at week 4, and 71% at week 12, with increasing rates of complete response. Treatment was more effective if administered as second-line option, and even in patients who previously failed eltrombopag (Feng Y et al.). An observational, retrospective study reported 14 years (2008 – 2022) of experience with TPO-mimetics in Barcelona, where 77 patients were treated, 57 with eltrombopag, 19 with romiplostim and 1 with avatrombopag. 89.6% of patients responded, treatment was successfully discontinued in 26% of them. 36% of patients switched the TPO-mimetic, and in 50% of cases switching was effective (Garcia-Pallarols F. et al.). Another single-center report from Spain retrospectively evaluated 96 patients treated with romiplostim or eltrombopag between 2010 and 2022. Response rates were similar to those previously reported, with a complete response rate of 86% with romiplostim and 70% with eltrombopag, and a discontinuation obtained in nearly 25% of patients (Martinez C. et al.).

A meta-analysis including five randomized controlled trials of rituximab + standard of care vs standard of care (463 patients in total) found that rituximab increased short-term (within 3 months) partial response and long-term (>6 months) partial and complete response, with a trend towards more infections in the rituximab arm. Data concerning follow-up longer than 12 months are scarce (Eshaghpour A et al.).