01 February 2021

Intensive chemotherapy plus immunotherapy may significantly improve outcomes for patients with lymphoma that has spread to the brain, British researchers have reported.

The international study was led in the UK by Dr Kate Cwynarski of University College London and colleagues, and published in the Lancet Haematology.

Secondary central nervous system (CNS) lymphoma can occur in patients with diffuse large B-cell lymphoma. Although rare, this spread of the lymphoma to the brain or spine is usually lethal. Patients are currently treated with high-dose-methotrexate-based chemotherapy and autologous stem cell transplant, but this is often unsuccessful.

The researchers undertook a trial called MARIETTA of intensified chemoimmunotherapy with autologous stem cell transplant, on 75 patients in four countries.

The chemotherapy plus immunotherapy regimens were known as MATRix and RICE. Three courses of each were given, before stem cell transplant. Certain very high-risk patients also received the R‑CHOP chemotherapy regimen.

By one year after recruitment to the trial, the MATRix-RICE treatment prevented the condition from worsening in 58% of the patients. Among those who had stem cell transplant, 100% had not worsened in a year.

After two years, 46% of patients showed progression-free survival. The rate was 83% for those patients who received the transplant.

The treatment regimen appeared to be more successful for patients whose disease had spread at diagnosis, with a two-year progression free survival of 71%, compared to 28% for patients who had been recruited to the trial because of a relapse to the CNS.

However, serious adverse events were experienced by 56%, often fever, low white blood cells, and infections.

Dr Cwynarski said: “The MARIETTA trial has meant patients who may have had just months to live are alive and living well years after being diagnosed. It is incredible to be able to sign DVLA forms for many of my patients treated with this approach, as you can’t drive until you have been clear of treatment for two years and are well, which really brought home the impact this study has had.”


Ferreri AJM, Doorduijn JK, Re A, Cabras MG, Smith J, Ilariucci F, Luppi M, Calimeri T, Cattaneo C, Khwaja J, Botto B, Cellini C, Nassi L, Linton K, McKay P, Olivieri J, Patti C, Re F, Fanni A, Singh V, Bromberg JEC, Cozens K, Gastaldi E, Bernardi M, Cascavilla N, Davies A, Fox CP, Frezzato M, Osborne W, Liberati AM, Novak U, Zambello R, Zucca E, Cwynarski K, for the International Extranodal Lymphoma Study Group (IELSG) (2021) “MATRIX-RICE therapy and autologous transplant in diffuse large B-cell lymphoma with CNS involvement: a phase II trial of the international extranodal lymphoma study group.” Lancet Haematology, doi: 10.1016/S2352-3026(20)30366-5



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