ASCT, WBRT ‘Effective’ First-Line Consolidation Therapy For Primary CNS Lymphoma

Both autologous stem cell transplantation and whole-brain radiotherapy regimens met the threshold for efficacy as consolidation treatments for primary CNS lymphoma

medwireNews: Both whole-brain radiotherapy (WBRT) and intensive chemotherapy for autologous stem cell transplantation (ASCT) are effective first-line consolidative therapies for primary central nervous system (CNS) lymphoma in patients aged up to 60 years, research suggests. 

The phase II trial participants were all given induction therapy consisting of two cycles of rituximab, methotrexate, carmustine and prednisone, followed by two cycles of rituximab plus cytarabine, the PRECIS investigators explain. 

The PRECIS study patients were then randomly assigned to receive ASCT plus intensive chemotherapy with thiotepa, busulfan and cyclophosphamide plus Peg-filgrastim, or to receive 40 Gy of radiation in 2-Gy fractions. 

Carole Soussain, from Institut Curie in Saint-Cloud, France, and co-authors report that “[b]oth treatments achieved the predetermined efficacy threshold”, defined as at least 2 years of disease-free survival for at least 24 of the 70 patients assigned to each regimen. 

Specifically, after a median of 33–34 months of follow-up, the primary endpoint of 2-year progression-free survival (PFS) in the first 38 patients of each arm to complete treatment was achieved by 87% of those treated with ASCT and 63% of the WBRT group. 

The corresponding 2-year PFS rates in per-protocol analysis for the 44 patients who completed ASCT and the 53 patients who completed WBRT were 86.2% and 66.9%, with similar outcomes noted when only assessing patients who had responded to induction therapy.  

Furthermore, intention-to-treat analysis of 66 patients in both the ASCT and WBRT arms gave 2-year PFS rates of 70% versus 58%, and 4-year rates of 65% versus 40%. The 2-year and 4-years rates of overall survival (OS) were 66% versus 75%, and 66% versus 64%, respectively. 

“Despite a higher number of relapses in the WBRT arm, OS was similar in both groups, probably because of the combined effect of the salvage treatment followed by ASCT offered to a significant proportion of patients in the WBRT arm, and the [treatment-related mortality] of protocol ASCT”, the researchers hypothesize.

Writing in the Journal of Clinical Oncology, the authors explain that the noncomparative trial design “precludes firm conclusions regarding the superiority of one type of consolidation.”  

Nevertheless, they point to an exploratory analysis of event-free survival which “showed a significant difference in favor of the ASCT [group]”, with 2-year postconsolidation therapy rates of 87% versus 69%. 

Neurocognitive assessments were completed by patients for up to 36 months after consolidation therapy; the investigators say that executive function tests showed “a substantial and clinically relevant proportion of patients who exhibited a poorer score after WBRT and an improved score after ASCT over time.” 

Discussing treatment-related toxicity, the researchers report that the WBRT patients experienced few grade 3 or more severe side effects, with one incidence of nausea and another of fatigue, along with four cases of alopecia. 

All patients treated with ASCT experienced reversible alopecia, febrile neutropenia and grade 4 cytopenia. In addition, 77% had grade 3 or more severe mucositis, while electrolyte disorders and neuropsychiatric disturbances occurred in 16% each. Four patients died from infectious complications and there was one death from an unknown cause. 

Taking into consideration the high relapse rate after WBRT and the associated cognitive decline, the researchers believe that the evidence may not “support this modality of consolidation” and that “ASCT seems to be a valid alternative, keeping in mind the risk of [treatment-related mortality]”. 

They conclude: “Additional studies aimed at identifying prognostic factors at diagnosis and at the end of the induction treatment might help define the most appropriate consolidation treatment on the basis of patient parameters.” 

 

Reference 

Houillier C, Taillandier L, Dureau S, et al. Radiotherapy or autologous stem-cell transplantation for primary CNS lymphoma in patients 60 years of age and younger: Results of the Intergroup ANOCEF-GOELAMS randomized phase II PRECIS study . J Clin Oncol; Advance online publication 20 February 2019. DOI: 10.1200/JCO.18.00306

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