Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions.

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

Impact of blinatumomab on patient outcomes in relapsed/refractory acute lymphoblastic leukemia: evidence to date.

Relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is associated with a poor prognosis in both children and adults. Traditionally, there were limited options for salvage therapy, which consisted mostly of conventional chemotherapy. However, in the past 5 years, novel agents have changed our treatment strategies in this population. Blinatumomab, a bispecific CD19 directed CD3 T-cell engager, has shown to be effective in both minimal residual disease and R/R B-cell ALL. In R/R B-cell ALL, blinatumomab was associated with an improved median overall survival of 7.7 months vs 4.0 months with traditional chemotherapy (HR for death, 0.71; 95% CI, 0.55-0.93; P=0.01). It has distinctive side effects as compared to chemotherapy, specifically cytokine release syndrome and neurological toxicities. When compared to standard of care chemotherapy, patients have higher quality of life scores and less financial burden. Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, blinatumomab-treated patients fared better and had a longer time to deterioration or death (global health status/quality of life subscale: HR 0.66; 95% CI 0.48-0.92; P=0.009) compared to conventional chemotherapy. Using an incremental cost effective ratio threshold of US$150,000 per quality adjusted life year, blinatumomab was determined to be more cost effective compared to chemotherapy with a probability of 73.7%. This review summarizes the current and future data with blinatumomab in R/R B-cell ALL in the adult and pediatric population.