Background
PRECIS (ANOCEF-GOELAMS intergroup) was a randomized phase II trial evaluating ASCT versus whole-brain radiotherapy (WBRT) as consolidation for patients aged ≤60 years with newly diagnosed PCNSL who achieved CR or PR after HD-MTX–based induction (R-MBVP: rituximab, methotrexate, VP-16/etoposide, BCNU/carmustine, prednisone). PRECIS complemented IELSG-32 Part 2's ASCT-vs-WBRT comparison, using a different induction backbone (R-MBVP) and a slightly younger cohort.
Interventions and follow up
Arm A (Control): Whole-brain radiotherapy 40 Gy in 20 fractions, with optional boost to residual disease
Arm B (Experimental): Autologous stem cell transplantation with thiotepa + busulfan (TBC) or thiotepa + BCNU conditioning
Population: n=140 (71 ASCT, 69 WBRT); 1:1; age ≤60; in CR or PR after 4 cycles R-MBVP
Primary endpoint: 2-year progression-free survival; secondary: OS, neurocognitive function, safety
mFollow up: 51 months
Arm B (Experimental): Autologous stem cell transplantation with thiotepa + busulfan (TBC) or thiotepa + BCNU conditioning
Population: n=140 (71 ASCT, 69 WBRT); 1:1; age ≤60; in CR or PR after 4 cycles R-MBVP
Primary endpoint: 2-year progression-free survival; secondary: OS, neurocognitive function, safety
mFollow up: 51 months
Results
2-yr PFS: ASCT 87% vs WBRT 63% (HR 0.52, 95% CI 0.30–0.89, P=.03)
2-yr OS: no significant difference; OS analysis underpowered
Neurocognitive function: significantly worse with WBRT (attention, executive function) at 12 months; preserved with ASCT
Leukoencephalopathy: more frequent post-WBRT on MRI
2-yr OS: no significant difference; OS analysis underpowered
Neurocognitive function: significantly worse with WBRT (attention, executive function) at 12 months; preserved with ASCT
Leukoencephalopathy: more frequent post-WBRT on MRI
Adverse events
Hematologic (ASCT): expected grade ≥3 cytopenias with TBC conditioning; mucositis and febrile neutropenia common
Treatment-related mortality (ASCT): reported in the transplant arm; requires careful patient selection
Neurologic (WBRT): objective cognitive decline and leukoencephalopathy more frequent than with ASCT
Tolerability: WBRT acute toxicity mild (fatigue) but delayed neurotoxicity dominated long-term morbidity
Treatment-related mortality (ASCT): reported in the transplant arm; requires careful patient selection
Neurologic (WBRT): objective cognitive decline and leukoencephalopathy more frequent than with ASCT
Tolerability: WBRT acute toxicity mild (fatigue) but delayed neurotoxicity dominated long-term morbidity
Conclusions
ASCT consolidation significantly improved 2-year PFS (87% vs 63%, HR 0.52) compared to WBRT in patients aged ≤60 years with PCNSL in response after HD-MTX–based induction, with substantially better preservation of neurocognitive function, establishing ASCT as a standard-of-care consolidation for fit younger PCNSL patients in CR or PR.
Key Limitations
Relatively small randomized phase II (n=140) powered for PFS, with OS analysis underpowered. Age ≤60 limits generalizability to older patients, who represent the majority of PCNSL cases. R-MBVP induction is not universally adopted (MATRix is the more widely used contemporary backbone). ASCT treatment-related mortality must be weighed against WBRT's delayed neurotoxicity. Patients in PR (vs CR) at consolidation had inferior outcomes. Comparison to observation/maintenance strategies was not included.
Clinical Context
PRECIS confirmed that ASCT consolidation is superior to WBRT for PFS in young fit PCNSL patients (consistent with IELSG-32 Part 2), establishing the paradigm of HD-MTX–based induction followed by ASCT consolidation for fit patients aged ≤65 with good performance status. The major management challenge remains the elderly population (median onset ~65–70 years) who cannot tolerate ASCT; the ANOCEF-GOELAMS elderly trial (Omuro, Lancet Haematol 2015) addresses that group. Ongoing trials explore BTK inhibitors (ibrutinib, zanubrutinib) in induction/consolidation and post-ASCT maintenance.