Page 161 - Haematologica Vol. 109 - July 2024

ARTICLE - Sovleplenib Syk inhibitor in R/R B-cell tumors
Y. Song et al.
a potential subsequent treatment option in patients who cannot tolerate or become resistant to BTKi.
The target inhibition based on the IC50 indicated that the onset dose of sovleplenib was 400 mg q.d.. At 400 and 600 mg q.d., the coverage time of target inhibition was over 24 hours according to the IC50.
Microenvironment-related biomarkers may predict clinical outcomes.29 BCR activation and co-stimulation by CD40+ T cells promote the secretion of CCL17 and CCL22, where these two chemokines could potentially induce trans-en- dothelial migration of activated T cells.30 Monocyte-de- rived nurse-like cells attract and protect leukemic CLL cells through secretion of chemokines, such as CXCL12 and CXCL13, thus promoting CLL disease progression, as demonstrated in CLL animal models.30,31 While in our study, a distinct reduction in CCL22, CCL17 and CXCL13 was ob- served in cohorts A, B and D, which indicates the contri- bution of sovleplenib to the tumor microenvironment.17,32,33 Sovleplenib reduced biomarker levels consistently during dose escalation; however, a statistically significant dose-de- pendent correlation was not observed, similar to previous results seen in a dual SYK/JAK inhibitor.34
Limitations of this study include its single-arm design, small sample size and enrollment of Chinese patients only. Additionally, long-term overall survival data were not collected.
In conclusion, sovleplenib demonstrated acceptable tol- erability in B-cell lymphomas patients; encouraging an- ti-tumor activities were observed, especially in CLL/SLL and FL. Further research is warranted to determine po- tential biomarkers to select patients that may be primed to benefit from Syk inhibitors in relapsed/refractory B-cell
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Disclosures
HY, SFu, SFan, QX, JW, XJ, GD, WS are employees of HUTCHMED Limited.
Contributions
HY, SFan and JZ conceptualized and designed the study. HY, SFu, SFan, QX, JW, XJ, GD and WS provided administrative support for study conduct. YS, JC, QZ, CL, LQ, JQ, HZhang, WL, LL, HJ, KZ, WZ, LZhang, DL, LZou, HYang, WQ, HZ and JH provided provision of study material or patients. YS, JC, QZ, CL, LQ, JQ, HZhang, WL, LL, HJ, KZ, WZ, LZhang, DL, LZou, HYang, WQ, HZ and JH performed the research and collected the data. QX analyzed the data. HY, SFu, SFan, QX, JW, XJ and GD interpreted the results. All authors had full access to study data, drafted, reviewed and approved the manuscript for submission.
Acknowledgments
The authors would like to thank all patients and their fami- lies, the investigators, and all staff who participated in this study. Medical writing support was provided by Deirdre Kelly (Parexel), in accordance with Good Publication Practice 3 guidelines.
Funding
This study was sponsored by HUTCHMED Limited.
Data-sharing statement
Individual data will not be made available.
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