ASCT May Offer Alternative To WBRT For CNS Lymphoma Consolidation Therapy

Autologous stem-cell transplantation consolidation after first-line chemoimmunotherapy for central nervous system lymphoma is feasible and may avoid the risk of cognitive impairment

medwireNews: Autologous stem-cell transplantation (ASCT) is an effective consolidation therapy option for patients with primary central nervous system (CNS) lymphoma who have responded to high-dose methotrexate-based chemoimmunotherapy, suggest phase II trial findings.

While both ASCT and whole-brain radiotherapy (WBRT) were found to be “feasible, safe, active and effective” consolidation strategies, the investigators report that patients who underwent WBRT had significant impairments in some tests of attention and executive function in the period immediately after treatment and up to 2 years later, whereas these measures and quality of life had significantly improved for the ASCT group.

“For such patients, the effects of treatments on cognitive functions and quality of life should be considered at the time of therapeutic decision”, recommend Andrés Ferreri, from IRCCS San Raffaele Scientific Institute in Milan, Italy, and co-authors in The Lancet Haematology

The International Extranodal Lymphoma Study Group (IELSG)32 trial’s initial randomisation compared use of methotrexate, cytarabine, thiotepa and rituximab (MATRix) in patients aged 18–70 years with newly diagnosed CNS lymphoma versus methotrexate plus cytarabine given alone or with rituximab. As previously reported, MATRix achieved a significantly higher rate of complete remission and overall response than the other regimens, resulting in significantly longer overall survival and progression-free survival (PFS), the investigators say.

The current article focusses on the second IELSG32 randomisation for the participants who achieved a response or stable disease with their induction regimen. These patients were assigned to receive WBRT within 4 weeks after induction (4–10 MeV photons given in five 180 cGy fractions per week) or ASCT preceded by a high-dose chemotherapy regimen of carmustine 400 mg/m2 6 days beforehand and thiotepa 5 mg/kg every 12 hours on days 5 and 4 beforehand.

Both the WBRT and ASCT trial arms met the predetermined efficacy threshold of at least 40 of the first 52 treated patients in each group being free from progression at 2 years. Two-year PFS did not significantly between the groups at 80% and 69%, respectively.

“Accordingly, MATRix combination followed by ASCT should be considered as the new standard treatment for these patients, and as the control group for future randomised trials”, conclude Andrés Ferreri et al.

Both consolidation strategies were “well tolerated” and grade 4 nonhaematological toxicity was “uncommon” in both groups, the investigators add, but haematological toxicity was more common with ASCT. Grade 4 thrombocytopenia and neutropenia occurred in 90% and 88% of ASCT patients versus 2% and 5% of WBRT patients, respectively. Two patients given ASCT died from infection.

The researchers conclude: “From a methodological standpoint, the IELSG32 trial is a model that demonstrates that multinational, well designed, well conducted randomised trials are feasible, can reach the accrual goal in a reasonable timeframe, and represent the most important route to progress in the field of primary CNS lymphoma.”

Reference

Ferreri AJM, Cwynarski K, Pulczynski E, et al. Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Study Group-32 phase 2 trial. Lancet Haematol; Advance online publication 17 October 2017. DOI: http://dx.doi.org/10.1016/S2352-3026(17)30174-6

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