Prophylactic High-Dose Methotrexate Does Not Improve Outcomes in High-Risk DLBCL

Prophylactic high-dose methotrexate (HD-MTX) use in patients with diffuse large B-cell lymphoma (DLBCL) at high risk for central nervous system (CNS) relapse did not have improved CNS relapse rates or survival, according to a real-world study published in Blood Advances.  

“In the absence of randomized controlled trials, the role of HD-MTX as CNS prophylaxis and its effect on survival outcomes in patients with DLBCL at high risk for CNS relapse are controversial,” wrote researchers. “This is the first study to evaluate and compare the efficacy of prophylactic HD-MTX by the initial treatment intent.” 

The retrospective study included 258 patients treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy between August 2013 and July 2018 at Asan Medical Center in Seoul, Korea. Patients were newly diagnosed with DLBCL and considered at high risk for CNS relapse. Researchers reviewed each patient’s medical record to identify the physician’s initial treatment intent (ITT): 128 patients had an ITT of prophylactic HD-MTX and were assigned to the ITT HD-MTX group, and 130 patients did not have an ITT of prophylactic HD-MTX and were assigned to the non-ITT HD-MTX group. 

The CNS relapse rate did not differ significantly between the groups, according to the study. The 2-year CNS relapse was 12.4% for the ITT HD-MTX group and 13.9% for the non-ITT HD-MTX group. 

Three-year progression-free survival rates were 62.4% in the ITT HD-MTX group and 64.5% in the non-ITT HD-MTX group. Overall survival rates were 71.7% in the ITT HD-MTX group and 71.4% in the non-ITT HD-MTX group, researchers reported.

Regarding toxicities, the ITT HD-MTX group had increased incidence of grade ≥ 3 oral mucositis and elevated alanine aminotransferase compared with the non-ITT HD-MTX group. 

“Another vital issue to consider is that HD-MTX treatment requires hospitalization because intensive hydration and leucovorin rescue is needed, which increases the medical costs,” researchers wrote. “Taken together, in the absence of clear evidence for a benefit of HD-MTX treatment on CNS relapse and survival outcomes, those potential risks should be considered before incorporating HD-MTX into standard R-CHOP chemotherapy.”

Reference:
Jeong H, Cho H, Kim H, et al. Efficacy and safety of prophylactic high-dose MTX in high-risk DLBCL: a treatment intent-based analysis. Blood Adv. 2021;5(8):2142-2152. doi:10.1182/bloodadvances.2020003947