Dr Grommes on Treatment Approaches in R/R PCNSL

BTK inhibitors have changed what we do [for patients with] PCNSL.

Christian Grommes, MD, an associate attending physician at Memorial Sloan Kettering Cancer Center, discusses the navigation of treatment for patients with relapsed/refractory primary central nervous system lymphoma (PCNSL), specifically how BTK inhibitors and CAR T-cell therapy fit into the equation.

BTK inhibitors and CAR T-cell therapy have emerged as important treatment approaches for patients with relapsed/refractory PCNSL, expanding therapeutic options in a disease with historically limited effective therapies, Grommes said. BTK inhibitors, which are administered as continuous oral therapy, and agents such as ibrutinib (Imbruvica) and zanubrutinib (Brukinsa) have been incorporated into the National Comprehensive Cancer Network guidelines.

Notably, the novel BTK inhibitor tirabrutinib demonstrated promising efficacy in patients with relapsed/refractory PCNSL in the phase 2 PROSPECT trial (NCT04947319) and is under further investigation in the phase 3 IGNITE trial (NCT07104032), which is evaluating the agent as monotherapy vs rituximab (Rituxan) plus temozolomide (Temodar) in patients with relapsed/refractory PCNSL.

Beyond the salvage setting, BTK inhibitors are also being explored in frontline treatment strategies, Grommes explained, underscoring their growing role across the disease continuum.

CAR T-cell therapy represents a distinct therapeutic approach, Grommes continued. Although initially established as a treatment in systemic diffuse large B-cell lymphoma, its role has expanded in PCNSL, including the February 2026 update that removed the prior limitations of Use for axicabtagene ciloleucel (Yescarta) in patients with relapsed/refractory PCNSL. Unlike BTK inhibitors, CAR T-cell therapy is administered as a one-time cellular therapy with a unique efficacy and safety profile, requiring different patient selection and toxicity management considerations, Grommes explained.

Ongoing clinical trials are evaluating CAR T-cell therapy earlier in the treatment course, including as consolidation, while additional studies are exploring combinations and sequencing strategies with BTK inhibitors. Together, these advances are reshaping the management of relapsed/refractory PCNSL and offering the potential for more durable disease control through complementary targeted and cellular therapeutic approaches, Grommes said.