Rituximab, Acalabrutinib, and Durvalumab for Primary Central Nervous System Lymphoma: A Single-Arm, Phase Ib,...

Area of Science:

• Neuro-oncology
• Hematology
• Clinical Pharmacology

Background:

• Primary central nervous system lymphoma (PCNSL) presents significant challenges due to poor prognosis and limited therapeutic options.
• Existing treatments for PCNSL often have suboptimal outcomes, necessitating novel therapeutic strategies.

Purpose of the Study:

• To evaluate the safety, tolerability, and preliminary efficacy of a combination therapy (RAD) in patients with relapsed/refractory PCNSL.
• To determine the recommended phase 2 dose (RP2D) for the RAD regimen in this patient population.

Main Methods:

• A phase 1b dose-escalation and expansion study was conducted.
• Patients received rituximab, acalabrutinib (once or twice daily), and durvalumab, with safety and response endpoints assessed.

Main Results:

• The RAD regimen was feasible, with no dose-limiting toxicities observed at dose level 2.
• An overall response rate of 62.5% was observed in evaluable patients, with a complete response rate of 12.5%.
• Median overall survival was 11.9 months and progression-free survival was 4.3 months, with improved outcomes for responders.

Conclusions:

• The RAD regimen is a feasible treatment option for patients with relapsed/refractory PCNSL.
• The combination therapy demonstrates potential clinical activity, warranting further investigation in larger trials.