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Phase 2 IELSG32 Trial: Advancing Treatment for Primary Central Nervous System Lymphoma

April, 04, 2023 | Lymphoma

KEY TAKEAWAYS

  • The phase 2 IELSG32 trial evaluated the efficacy of different treatment arms for (PCNSL) in HIV-negative adults ≤70 years.
  • The primary aim was to assess (OS), the efficacy of salvage therapy, late complications, secondary tumors, and cognitive impairment
  • Enrolled patients were randomized to receive (arm A), methotrexate-cytarabine-rituximab (B), or (MATRix; arm C).
  • After a median follow-up of 88 months, results showed that MATRix was associated with excellent long-lasting outcomes, with a 7-year OS of 21%, 37%, and 56%, respectively, for arms A, B, and C.
  • Patients who received WBRT experienced impairment, whereas patients undergoing ASCT experienced an improvement in these functions, memory, and quality of life.

The IELSG32 trial enrolled 219 HIV-negative adults younger than 70 diagnosed with primary CNS lymphoma (PCNSL). Methotrexate and cytarabine (arm A), methotrexate and cytarabine with rituximab (arm B), or methotrexate and cytarabine with thiotepa and rituximab (arm C) were randomly assigned to the enrolled patients (MATRix; arm C). Patients considered to have a responsive/stable disease were randomly assigned to receive either whole-brain irradiation (WBRT) or carmustine-thiotepa-conditioned autologous transplantation (ASCT).

After a median follow-up of 30 months, initial findings demonstrated a marked improvement in outcome due to MATRix, with WBRT and ASCT performing similarly well. However, more time is needed to accurately assess OS, salvage therapy efficacy, late complications, secondary tumors, and cognitive impairment.

Here, at a median follow-up of 88 months, we present the findings of this study. The primary results demonstrated that MATRix was linked to a favorable long-term outcome, with a 7-year OS of 21%, 37%, and 56% for arms A, B, and C, respectively. ABout 70% of patients given MATRix and consolidation survived for seven years. Since arm B performed better than arm A, including rituximab may have been beneficial. It was determined that WBRT and ASCT were equally effective. Late relapse patients retreated with methotrexate saw the only benefit from salvage therapy. Eight patients, or 4%, were diagnosed with a second malignancy. It’s encouraging that MATRix and ASCT did not increase the risk of dying from causes other than cancer. Attention and executive functions were impaired in WBRT patients but improved in ASCT patients, who also saw improved memory and quality of life.

Source: https://pubmed.ncbi.nlm.nih.gov/35562406/

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT01011920

Ferreri AJM, Cwynarski K, Pulczynski E, Fox CP, Schorb E, Celico C, Falautano M, Nonis A, La Rosée P, Binder M, Fabbri A, Ilariucci F, Krampera M, Roth A, Hemmaway C, Johnson PW, Linton KM, Pukrop T, Gørløv JS, Balzarotti M, Hess G, Keller U, Stilgenbauer S, Panse J, Tucci A, Orsucci L, Pisani F, Zanni M, Krause SW, Schmoll HJ, Hertenstein B, Rummel M, Smith J, Thurner L, Cabras G, Pennese E, Ponzoni M, Deckert M, Politi LS, Finke J, Ferranti A, Cozens K, Burger E, Ielmini N, Cavalli F, Zucca E, Illerhaus G; IELSG32 study investigators. Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial. Leukemia. 2022 Jul;36(7):1870-1878. doi: 10.1038/s41375-022-01582-5. Epub 2022 May 13. PMID: 35562406.

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