Rituximab Fails To Show ‘Clear Benefit’ For First-Line Primary CNS Lymphoma

Adding rituximab to methotrexate-based chemotherapy does not significantly improve event-free survival for patients with treatment-naïve primary central nervous system lymphoma

medwireNews: Combining rituximab with first-line chemotherapy does not extend event-free survival (EFS) in patients with primary central nervous system (CNS) lymphoma, suggest findings from the HOVON 105/ALLG NHL 24 trial. 

“[T]he results of this study do not support the use of rituximab as a component of standard treatment in primary CNS lymphoma”, the investigators say in The Lancet Oncology.

The primary endpoint of EFS at 1 year was achieved by 52% of the 99 patients randomly assigned to receive open-label methotrexate, carmustine, teniposide and prednisone (MBVP) plus intravenous rituximab 375 mg/m2 on days 0, 7, 14 and 21 of cycle 1, and days 0 and 14 of cycle 2. 

Multivariate analysis adjusting for age and ECOG–WHO performance score stratum confirmed that this rate did not significantly differ from the 1-year EFS rate of 49% for the 100 patients who were given MBVP alone, report Jacoline Bromberg, from Erasmus MC Cancer Institute in Rotterdam, the Netherlands, and co-authors. 

The rituximab plus MBVP and control arm patients were also comparable with regard to the 1-year rate of progression-free survival (65 vs 58%) and the rate of response to induction chemotherapy (86 vs 86%).  

“We found no evidence that treatment with [rituximab]–MBVP increased the number of complete responses or unconfirmed complete responses compared with MBVP”, the researchers say. 

Median overall survival was not reached for the rituximab arm versus 56.7 months for the controls, giving an adjusted hazard ratio (HR) for death of 0.93 that was not significant, although the team admits that “it is too early to report details regarding overall survival or rescue treatments that might have affected this outcome.”

Jacoline Bromberg et al also performed a post-hoc analysis as only trial participants aged 60 years and younger received consolidation radiotherapy. While median EFS with or without rituximab did not significantly differ for patients aged over 60 years (4.2 vs 8.3 months), median EFS was significantly longer with rituximab in the younger population, at 59.9 versus 19.7 months, giving a HR of 0.56.

The researchers emphasize that “[t]hese results should be interpreted with caution because they are from an unplanned subgroup analysis and are therefore hypothesis generating only”, but believe that “an interaction between whole-brain radiotherapy and rituximab could be postulated.”

Commentators Benjamin Kasenda and Gerald Illerhaus, from Stuttgart Cancer Centre in Germany, say this subgroup finding “creates uncertainty regarding the overall results” and warn against neglecting the “total body of clinical evidence”, including findings from the earlier phase II IELSG32 trial, which showed a survival benefit in this population.

“Considering the established benefit for rituximab in systemic diffuse large B-cell lymphoma and results from both randomised trials in primary CNS lymphoma, we believe rituximab should remain an indispensable component in the treatment of patients with primary CNS lymphoma, irrespective of age”, they recommend.

 

References 

Bromberg JEC, Issa S, Bakunina K, et al. Rituximab in patients with primary CNS lymphoma (HOV ON 105/ALLG NHL 24): a randomised , open-label, phase 3 intergroup study . Lancet Oncol; Advance online publication 7 January 2019. http://dx.doi.org/10.1016/S1470-2045(18)30747-2

Kasenda B, Illerhaus G. CNS border posts against rituximab? Lancet Oncol; Advance online publication 7 January 2019. http://dx.doi.org/10.1016/ S1470-2045(18)30829-5

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