Publications

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.

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, is an aggressive and biologically heterogeneous disease. Risk stratification and treatment algorithms vary based on stage of disease and bulk along with other clinical and biological factors, including the International Prognostic Index, cell of origin, and other molecular subsets. Rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the current standard of care and cures more than 60% of patients. The role of radiotherapy is largely restricted to patients with limited-stage disease. In elderly patients, geriatric assessments of baseline fitness and functional status help optimize therapy based on the balance of efficacy and toxicity. While numerous randomized trials have failed to improve upon R-CHOP, a recent press release from the POLARIX trial (NCT03274492) suggests that adding polatuzumab vedotin (Polivy) to rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) improves progression-free survival and may replace R-CHOP in eligible patients. Ongoing trials are exploring frontline therapy that integrates other novel agents, including various small molecules, bispecific antibodies, and chimeric antigen receptor T-cell therapy, with promising preliminary results. Defining a population of patients with high-risk disease in whom R-CHOP is not effective is critical. Patient selection based on refining molecular subsets, quantitative PET metrics such as metabolic tumor volume, and dynamic risk assessments using interim PET and circulating tumor DNA analysis may allow for a personalized, response-adapted approach that will further improve outcomes in DLBCL.