Is WBRT or ASCT Better Consolidation for Younger Patients With CNS Lymphoma?

Consolidation treatment with autologous stem cell transplantation (ASCT) or whole-brain radiation therapy (WBRT) was effective as first-line treatment in patients age 60 years or younger with central nervous system (CNS) lymphoma, according to phase II results of the PRECIS study.

However, the high relapse rate and neuropsychological decline associated with 40-Gy WBRT do “not support this modality of consolidation, and ASCT seems to be a valid alternative,” reported Caroline Houillier, MD, of Groupe Hospitalier Universitaire Pitie-Salpetriere in Paris, and colleagues. These results were published in the Journal of Clinical Oncology.

High-dose methotrexate followed by WBRT has been a standard first-line treatment for primary CNS lymphoma, but is associated with delayed neurotoxicity. Intensive chemotherapy followed by ASCT has been shown to be feasible in relapsed or refractory CNS lymphoma and has had promising results in noncontrolled phase II studies as a first-line treatment.

In the PRECIS study, 140 patients age 18 to 60 years with untreated disease were given induction chemotherapy with rituximab, methotrexate, carmustine (BCNU), and prednisone, followed by rituximab and cytarabine, and then randomly assigned to WBRT (40 Gy) or ASCT. Transplant was combined with intensive chemotherapy with thiotepa, busulfan, and cyclophosphamide (TBC).

Both regimens achieved their predetermined efficacy thresholds, according to the researchers.

With a median follow-up of 33 months in the WBRT arm and 34 months in the ASCT arm, the 2-year progression-free survival rates were 63% and 87%, respectively.

“An exploratory comparative analysis of the event-free survival after consolidations showed a significant difference in favor of the ASCT, but the noncomparative design of this study precludes firm conclusions regarding the superiority of one type of consolidation,” the researchers wrote.

The overall response rate after induction therapy was 70%, a rate the researchers called “disappointing.” Patients assigned to WBRT had an overall response rate of 76% compared with 64% for patients in the ASCT arm. Twenty patients in the WBRT arm and 3 patients in the ASCT arm relapsed.

One patient in the WBRT arm and 5 patients (11%) in the ASCT arm died from toxicity.

Overall survival was similar between the two groups; however, the researchers noted that the similarity may be because of “the combined effect of the salvage treatment followed by ASCT offered to a significant proportion of patients in the WBRT arm, and the treatment-related mortality of ASCT.”

After WBRT, more than half of patients had a decrease in their neuropsychological test scores. In contrast, more than half of patients assigned to ASCT had an improvement in their test scores.

When deciding on a treatment, the researchers said the risks and benefits of each modality should be thoroughly discussed.

Commenting on the study, Michael Scordo, MD, of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center, told Cancer Network that the PRECIS study is a highly important clinical trial for the field, since it is only the second published multicenter randomized study aimed at determining whether WBRT or ASCT is the optimal first-line consolidation strategy for patients with primary CNS lymphoma.

“It has long been felt that WBRT is associated with more cognitive impairment than ASCT-the PRECIS study further validates this observation,” Scordo said. “Moreover, while both WBRT and ASCT remain effective consolidation strategies for patients with primary CNS lymphoma, the PRECIS study adds to the growing evidence that patients consolidated with ASCT have superior and durable remission rates.”

According to Scordo, the biggest query that remains in the field of ASCT for primary CNS lymphoma is understanding which conditioning chemotherapy regimen is optimal for these patients.

“PRECIS and other studies have shown that TBC conditioning is clearly effective and may be associated with better disease control than other regimens previously studied in this setting,” he said. “However, it is also associated with a significant incidence of grade 3 or higher adverse events and what appears to be a slightly higher treatment-related mortality than one would expect after a typical ASCT, even in patients < 60 years old. Future studies aimed at determining the optimal ASCT conditioning regimen to be used in patients with CNS lymphoma will be crucial.”