Adding rituximab to CHOP decreased risk for CNS in older patients with B-cell lymphoma

Treating elderly patients with CD20-positive lymphoma with rituximab plus CHOP-14 resulted in a lower incidence of CNS disease among patients, according to data from an analysis of the RICOVER-60 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group.

In the trial, 1,222 patients aged 61 to 80 with newly diagnosed aggressive B-cell lymphoma were randomly assigned to six or eight courses of CHOP every two weeks with or without rituximab (Rituxan, Genentech). Patients with disease in the bone marrow, testes, upper neck or head were assigned to CNS prophylaxis with intrathecal methotrexate.

The analysis included 1,217 patients, 58 of whom developed CNS. Fewer patients assigned to R-CHOP-14 experienced a CNS event (3.6%) compared with those not assigned to rituximab (5.9%). After CHOP-14 the estimated two-year incidence of CNS disease was 6.9% (95% CI, 4.5-9.3) compared with 4.1% (95% CI, 2.3-5.9) after R-CHOP-14. The relative risk for CNS disease among patients assigned to R-CHOP-14 was 0.58 (95% CI, 0.3-1.0).

Parenchymal CNS disease accounted for 50% of CNS events in the R-CHOP-14 arm compared with 75% in the CHOP-14 arm. However, the percentage of patients with meningeosis rose from 16.7% of CNS events in the CHOP-14 arm to 40.9% in patients in the R-CHOP-14 arm, according to the researchers. Simultaneous systemic disease was observed in 27.3% of patients assigned to R-CHOP-14 compared with 50% of those assigned to CHOP-14 alone. – by Stacey L. Adams

Boehme. Blood. 2009;113:3896-3902.

For all of us who treat patients with diffuse large B-cell lymphoma (DLBCL), especially those who are in the “elderly” age-group, this follow-up report from the investigators in Germany (further analysis of their results previously published in The Lancet Oncology. 2008;9:105) will be extremely useful. This report helps us to identify the clinical characteristics in elderly patients that are associated with increased risk for the development of CNS lymphoma. This report provides us with objective evidence that adding rituximab to CHOP certainly reduces the risk of developing CNS lymphoma but, unfortunately, this combination does not totally eliminate that risk. As the authors correctly point out, it has become virtually universal that rituximab is added in any regimen (CHOP or CHOP-like) we use today in treating DLBCL. This analysis also demonstrates that prophylaxis use of intrathecal methotrexate does not provide protection to DLBCL patients. In my mind, we still have something to learn from our colleagues in pediatric hematology-oncology, because over the past four decades, they have virtually been able to totally eliminate the occurrence of CNS disease in children with acute lymphocytic leukemia. That success came only after disciplined and meticulous step-by-step efforts in attacking and preventing CNS disease. Efforts and careful analysis of the results of large randomized trials as shown by our colleagues in Germany are movements in the right direction.

– Kanti Rai, MD

Chief, Division of Hematology-Oncology,
Long Island Jewish Medical Center, New York