Hematology Xagena

Xagena Mappa
Xagena Newsletter

Newly diagnosed primary central nervous system lymphoma: Ibrutinib-based combination therapy has exhibited therapeutic benefit

Ibrutinib ( Imbruvica ) has shown single-agent activity in relapse / refractory ( R/R ) primary central nervous system lymphoma ( PCNSL ), and the high dose Methotrexate ( HD-MTX ) has been the backbone of treatment of de-novo PCNSLs.
Combination therapy of HD-Methotrexate and Ibrutinib has recently shown activity in R/R PCNSLs.

Eleven newly diagnosed patients with primary central nervous system lymphoma who underwent combination therapy of HD-Methotrexate and Ibrutinib were analyzed for treatment response and safety profile.

HD-Methotrexate was given at 3.5 g/m2 every 2 weeks for a total of 8 doses.
Ibrutinib was held on days of HD-Methotrexate infusion until HD-Methotrexate clearance. Single-agent daily Ibrutinib was administered continuously after completion of induction therapy until disease progression, intolerable toxicity, or death.

Patients’ clinicopathologic characteristics were retrospectively reviewed and genomic traits were further analyzed.

Nine out of 11 patients have completed the induction phase of Ibrutinib-based combination therapy and received Ibrutinib maintenance in addition to two patients whose disease progressed during the therapy.

An objective response rate ( ORR ) of 82% ( 9/11 ) was observed, including 7 patients with complete response ( CR, 64% ) and 2 patients with partial response ( PR, 18% ).

The median progression-free survival ( PFS ) was 7.4 months while the median overall survival ( OS ) was not reached.

The combination therapy of HD-Methotrexate and Ibrutinib was well tolerated and has acceptable safety.

In addition, the presence of circulating tumor DNA ( ctDNA ) in cerebrospinal fluid ( CSF ) samples closely correlated with tumor response.
Sustained tumor responses were associated with the clearance of ctDNA from the CSF.

In conclusion, combination of Ibrutinib and HD-Methotrexate has acceptable safety and has demonstrated anti-tumor activity in newly diagnosed de-novo patients with primary central nervous system lymphoma.
The detection of ctDNA in CSF is feasible for monitoring tumor burden in PCNSL patients. ( Xagena )

Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020