Older patients with primary central nervous system lymphoma: Survival and prognostication across 20 U.S. cancer centers

Abstract

There is a paucity of large-scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly-diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60-88); at least one geriatric syndrome was present in 46%; the median Cumulative Index Ratings Scale-Geriatrics (CIRS-G) score was 6 (range, 0-27); and 36% had impairment in activities of daily living (ADL). The most common induction regimens were high-dose methotrexate (HD-MTX) ± rituximab; methotrexate, temozolomide, rituximab (MTR); and rituximab, methotrexate, procarbazine, vincristine (R-MPV). Overall, 70% of patients achieved remission, with 14% undergoing consolidative autologous stem cell transplant (ASCT) and 24% receiving maintenance. With 58-month median follow-up, median progression-free survival (PFS) and overall survival (OS) were 17 months (95% CI 13-22 months) and 43 months (95% CI 31-56 months), respectively. Three-year PFS and OS were highest with MTR (55% and 74%, respectively). With single-agent methotrexate ± rituximab, 3-year PFS and OS were 30% (p = .0002) and 47% (p = .0072). On multivariate analysis, increasing age at diagnosis and Cooperative Oncology Group (ECOG) performance status (PS) was associated with inferior PFS; age, hypoalbuminemia, higher CIRS-G score, and ECOG PS adversely affected OS. Among patients receiving maintenance, 3-year PFS was 65% versus 45% without maintenance (p = 0.02), with 3-year OS of 84% versus 61%, respectively (p = .0003). Altogether, outcomes in older PCNSL patients appeared optimized with HD-MTX combination induction regimens and maintenance therapy. Furthermore, several prognostic factors, including geriatric measures, were associated with inferior outcomes.

FIGURE 1

(A) Median PFS for the entire cohort of 539 patients was 17 months (95% CI 13–22 months). PFS at 36 months was 37% (955 CI 33–42). (B) Median OS was 43 months (95% CI 31–56 months). OS at 36 months was 53% (95% CI 48–57). (C). PFS for each of the three most common induction regimens, adjusted for significant pre-treatment variables. PFS was highest for patients treated with the MTR regimen. (D). OS for each of the three most common induction regimens, adjusted for significant pre-treatment variables. OS was highest for patients treated with the MTR regimen.

FIGURE 2

(A). PFS by age group at diagnosis. PFS was best for patients 60–70 years old at diagnosis and worse for those aged 80 and older. (B). OS by age group at diagnosis. OS was best for patients 60–70 years old at diagnosis and worse for those aged 80 and older. (C) CIRS-G score above 5 was associated with lower OS. Impaired ECOG PS was associated with worse PFS (D) and OS (E).

FIGURE 3

(A) Response to initial therapy significantly impacted survival. Patients who experienced CR after induction had the longest PFS, while patients with disease progression had drastically worse outcomes. (B) A similar trend was seen with regard to OS. When adjusted for pre-treatment variables, consolidative autologous SCT resulted in a statistically significant improvement in PFS (C), but not OS (D). Cytarabine consolidation did not affect PFS (E) but was associated with improved OS (F) Maintenance therapy resulted in improvements in both PFS (G) and OS (H).

FIGURE 4

Consolidative autologous stem cell transplant and maintenance therapy appeared to have a larger benefit on OS for patients in PR at the end of induction compared to CR. OS is depicted for patients in CR (A) and PR (B) at the time of ASCT. OS is depicted for patients who received maintenance therapy in CR (C) and PR (D). Consolidative radiation therapy did not improve OS (E).