Many patients with primary central nervous system lymphoma (PCNSL) experience rapid, aggressive progression of CNS malignancy. It is “accepted,” say researchers from Chonnam National University Hwasun Hospital in the Republic of Korea, that salvage therapy is beneficial and significantly improves survival in comparison to palliative care, but therapy options remain limited—mainly because few trials have been done. Several case reports have suggested that bendamustine has modest clinical activity against relapsed PCNSL, the researchers note, but its effect as part of combination salvage therapy in these patients has not been established. The study offers some validation of previous findings and new information about the benefits of a bendamustine-based combination regimen.
The researchers enrolled 10 patients, of whom 7 had refractory disease. All had previously been on high-dose methotrexate. Of the 3 relapsed patients, 1 entered the study at second relapse. The patients received either R-B(O)AD or R-BAD (rituximab, vincristine, bendamustine, cytarabine, dexamethasone) every 4 weeks for up to 4 cycles. Vincristine was omitted in 4 regimens, and dosages of bendamustine and cytarabine were reduced for 4 patients who were over 70.
The overall response rate for R-B(O)AD was 50%. One patient achieved complete response and 4 achieved partial response. The researchers observed “remarkable effects” on imaging in patients who responded. They attribute the activity to the anticipated synergy of bendamustine combined with cytarabine—even though disease in the majority of the patients had progressed despite previous treatment with cytarabine.
However, the synergistic effects also led to significant marrow depression; hematologic toxicity with R-B(O)AD was “considerable,” with grade 3 or 4 neutropenia and thrombocytopenia seen in more than 85% of treatment cycles. Moreover, 3 patients developed severe infection, all with involvement of the lungs. The researchers therefore amended the study protocol to reduce cytarabine dosage. While the toxicity is significant, the researchers say, it is manageable with the dose reduction and supportive care.
Bendamustine cerebrospinal fluid levels were minimal, but corresponded to plasma exposure and response to treatment in deep tumor locations.
Although the study is small, it supports the use of the bendamustine-based regimen as an effective salvage option, the researchers conclude, especially for patients who are no longer responding to methotrexate or have developed cumulative renal or neurotoxicity from treatment.
Kim T, Choi HY, Lee HS, et al. BMC Cancer. 2018;18(1):729