Page 160 - Haematologica Vol. 109 - July 2024

ARTICLE - Sovleplenib Syk inhibitor in R/R B-cell tumors Y. Song et al.
Figure 4. Duration of treatment in patients with follicular lymphoma in the dose-expansion phase. FL: follicular lymphoma; b.i.d.: twice daily; AE: adverse event; CR: complete response; PD: progressive disease; PR: partial response; PR-L: PR with increased lymphocyte count; q.d.: once daily; SD: stable disease.
mPFS of 11.0 months and mDOR not reached, indicating that this malignancy is distinctly susceptible to Syk inhibition. The Syk/FLT3 inhibitor TAK-659 has also been shown to achieve a high ORR of 89%, albeit in a small cohort (N=14) of FL patients.12,18,25 In contrast, modest anti-tumor activity in FL patients treated with entospletinib or fostamatinib was noted, with ORR of 10% and 17%, respectively, and mPFS of 4.6 and 5.7 months, respectively. The differences in ORR may be due to different prior treatment regimens, such as 96.9% versus 33.3% of patients with MZL, LPL/WM and FL (grades 1, 2, 3a) receiving prior anthracycline in our study versus that in entospletinib.18 Half of the FL patients in the study of TAK-659 had underwent prior autologous transplant.12,18,25 Our subgroup analysis indicated that FL pa- tients with prior Pi3K inhibitor treatment also experienced an encouraging tumor response (ORR, 66.7%; mDOR, 5.5 months; mPFS, 5.5 months), as did patients who received
prior anti-CD20 monoclonal antibody therapy (ORR, 59%; mDOR, 14.8 months; mPFS, 8.3 months). This could indi- cate that sovleplenib may be an option after anti-CD20, or indeed Pi3K inhibitor, treatment failure given that Syk signaling is upstream of Pi3K during BCR activation.28 Sovleplenib-mediated anti-tumor activity was also en- couraging in CLL/SLL, with an ORR of 56.3%, mDOR of 13.1 months and mPFS of 14.9 months. Previous Syk inhibitor studies with entospletinib, cerdulatinib and fostamatinib demonstrated ORR results of 33-61% in CLL/SLL patients, with an mPFS of 5.6-13.8 months.12,17,27 Current CLL/SLL first-line therapy includes chemotherapy, anti-CD20 immu- notherapy, BTKi and BCL-2 inhibitors. In CLL/SLL patients previously treated with BTKi, or or received ≥3 lines of treatments, sovleplenib showed a notable anti-tumor ac- tivity, with an ORR of 50%, mDOR of 14.7 months and mPFS of 16.5 months; therefore, sovleplenib may be explored as
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