A weekly dose of temsirolimus 75 mg was found to be active in patients with relapsed/refractory primary CNS lymphoma (PCNSL); however, only some patients achieved long-term control, a study published in the Journal of Clinical Oncology has shown.1
Prognosis for patients with relapsed/refractory PCNSL is poor. Approximately 25% of patients do not respond to first-line therapy, and more than 50% experience relapse. Although whole-brain radiotherapy is an effective salvage treatment, the modality exposes patients to a higher risk of late neurotoxicity than chemotherapy; therefore, salvage chemotherapy is preferred.
In this study, researchers investigated the efficacy of temsirolimus in patients with relapsed or refractory PCNSL. The phase II study (ClinicalTrials.gov NCT00942747) included 37 immunocompetent adults with histologically confirmed PCNSL who were not eligible for or had experienced treatment failure with high-dose methotrexate-based chemotherapy. Median age was 70 years; median time since last treatment was 3.9 months (range, 0.1 to 14.6 months).
Primary end point was overall response rate, including complete response (CR), CR unconfirmed, and partial response. Secondary end points included penetration into the cerebrospinal fluid (CSF), toxicity, progression-free survival, and overall survival.
The first 6 participants received temsirolimus 25 mg IV once per week; all consecutive patients received temsirolimus 75 mg IV once per week.
An overall response rate of 54% was seen, with 5 patients (13.5%) achieved CR, 3 (8%) achieved CR unconfirmed, and 12 (32.4%) achieved partial response. Median progression-free survival was 2.1 months (95% CI, 1.1 to 3.0 months).
The most frequent grade 3 or higher adverse events was hyperglycemia (11 patients [29.7%]), thrombocytopenia (8 patients [21.6%]), infection (7 patients [19%]), anemia (4 patients [10.8%]), and rash (3 patients [8.1%]).
Blood/CSF pairs were collected from 5 patients in the 25-mg cohort (10 pairs) and 4 patients in the 75-mg cohort (4 pairs). Mean maximum blood concentration for temsirolimus and its metabolite sirolimus was 292 ng/mL and 37.2 ng/mL, respectively, in the 25-mg cohort; and 484 ng/mL and 91.1 ng/mL, respectively, in the 75-mg cohort.
Study findings showed CSF concentration for temsirolimus was 2 ng/mL in 1 patient in the 75-mg cohort, but no drug was found in the CSF of any of the other patients. The researchers concluded that temsirolimus is active in relapsed/refractory PCNSL. Although some patients achieved long-term control, most responses were short lived. Therefore, further evaluation in combinations with other drugs may be warranted.
1. Korfel A, Schlegel U, Herrlinger U, et al. Phase II trial of temsirolimus for relapsed/refractory primary CNS lymphoma [published online ahead of print March 14, 2016]. J Clin Oncol. doi:10.1200/JCO.2015.64.9897.