Andrew M. Evens, DO, MSc from Robert Wood Johnson University Hospital and Rutgers Cancer Institute of New Jersey discusses the ASH 2020 abstract – 476 Real World (RW) Outcomes and Prognostication of Older Patients with Primary Central Nervous System Lymphoma (PCNSL) in the Contemporary Era.
Introducing:
The treatment of older patients (pts) with PCNSL is complicated because of the prevalence of comorbidities, fragility, and difficulty of chemotherapy delivery (CT). For older PCNSL pts, the optimum induction CT and consolidation regimens are uncertain. In addition, few large-scale forecasting studies are available, including the study of geriatric evaluations (GA). In 17 academic centers, we analyzed detailed features, patient trends, and outcomes with prognostication.
Methodology:
A broad RW retrospective analysis of newly diagnosed PCNSL pts (1/2008-1/2019) aged 60 years and over was conducted (yrs). Kaplan-Meier calculated survival rates, with variations measured by the log-rank test. We have comprehensive scores & other GAs for Cumulative Index Rating Scale-Geriatric (CIRS-G) scores. Through the Cox model, univariate correlations were extracted with variables p<0,05 entered into a multivariate (MVA) model stepwise.
Outcomes:
N=450 cases were confirmed for diagnosis & follow-up among the 491 initial cases. Clinical characteristics included: median age 71 years (60-88); male 47 percent; elevated LDH 30 percent; creatinine clearance 20 percent (median 81 ml/min) <60 ml/min; hemoglobin 8 percent <10 g/dL; and albumin 35 percent <3.5 g/dL. 21% had previous or concurrent malignancy in pts and 7% had a history of solid organ transplantation or autoimmune disease. In 96 percent (COO non-GC in 76 percent), histology was DLBCL with 98 percent expression of CD20. Immunohistochemistry showed double expression of MYC & BCL2 in 40 percent; in 10 percent of pts, EBER was noted (3/4 were PTLD pts). Brain parenchyma was involved in 94 percent of pts for disease placement, with 46 percent having a single site (54 percent > 1 site). With deep structure involvement in 20 percent and cerebellum in 5 percent, cerebral involvement prevailed in 75 percent. In 13 percent of pts, CSF participation was recorded in (unchecked in 26 percent ). The median CIRS-G score for GA at diagnosis was 6 (range 0-27) and 36 percent of impaired daily living self-care activities (ADLs) were noted. In addition, the geriatric syndrome was present in 45 percent of pts (i.e., dementia, delirium, depression, and/or falls).
Induction therapy included 91 percent of pts (of which 82 percent had rituximab (Rtx)) with CT and 8 percent with radiation therapy (RT). The most prevalent chemotherapy regimens were: high-dose methotrexate (HD MTX) or HD MTX with 38% Rtx (MR); HD MTX/procarbazine/vincristine (MPV) +/- 30% Rtx; 22% HD MTX/temozolomide/Rtx (MTR); 2% Rtx alone; and 2% HD MTX/cytarabine/thiotepa/Rtx (MATRIX) . For all pts, the median MTX dose was 3.5 g/m2 (range 1-8 g/m2) and for the three most common regimens (all g/m2): MTR 5.1; MR 5.4; MPV 3.1 (P<.0001). For induction response, 60% had a full response (CR), 18% had a partial response (PR), 6% had stable disease, and 16% had primary refractory disease. Induction CT was stopped in 21 percent of pts due to toxicity and the mortality associated with treatment was 7 percent. 14 percent had autologous stem cell transplantation (ASCT) out of 321 pts with CR or PR; 25 percent received consolidated CT, and 5 percent had RT. Temozolomide (n=22), lenalidomide (n=20) and HD MTX (n=15) were the most prevalent CT maintenance regimens. RT (n=40), MTX (n=39), temozolomide (n=14) and MTR (n=10) were the most common 2nd line therapies among pts experiencing relapse or progression; 2 pts eventually went on to receive ASCT.
With a median follow-up of 42 months (1-125), 3-yr PFS & OS were 38 percent & 52 percent, respectively, for all pts (Fig 1A/1B). Factors associated with inferior PFS for MVA were: old age (continuous HR 1.05, P<.001); anemia (HR 1.14, P=.0035); high CIRS-G (HR 1.038, P=0.017); and geriatric syndrome (HR 1.537, P=.0098) (Fig 1C); and advanced age (continuous HR 1.04, P=.01); low albumin (HR 2.203, P<.001); high CIRS-G (HR 1.053, P=.011); and geriatric syndrome (HR 1.851, P=.005); and low albumin (HR 2.203, P<.001); and high CIRS-G (HR 1.053, P=.011); and geriatric syndrome (HR 1.851, P=005) (Fig 1D). Increased HD MTX dosing in 500 mg/m2 increments was correlated with improved PFS (HR 0.958, P=.0002) & OS (HR 0.954, P=.001) across all pts; and improved PFS & OS vs MPV or MR (Fig 1E /1F) pts treated with MTR (Fig 1E /1F). Although adjusting for age, CIRS-G & geriatric syndrome, the favorable impact of MTR vs MR persisted. Additionally, enhanced findings were correlated with the use of Rtx (PFS HR 0.592, P<.0001; OS HR 0.528, P<0.0001). Finally, survival was substantially increased by pts achieving CR (Fig 1G/1H).
Findings:
There are suboptimal results for older pts with PCNSL, with 2/3 improving in the first few years. GA is a significant prognostic tool and may be used in future inquiries to stratify pts. In addition, better results were correlated with the use of Rtx, an improvement in the MTX dose, and the MTR protocol.