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Purpose <p>Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma that predominantly affects elderly individuals. High-dose methotrexate (HD-MTX)-based chemotherapy remains the mainstay of PCNSL treatment, but the optimal combination regimen for elderly patients remains undefined. Nimustine (ACNU), a nitrosourea with excellent blood–brain barrier penetration, has not been evaluated in combination with HD-MTX. We investigated the efficacy and safety of HD-MTX combined with ACNU in elderly PCNSL patients.</p> Methods <p>We retrospectively analyzed the cases of 17 untreated PCNSL patients (median age, 71 years) who received the MPA regimen consisting of HD-MTX, procarbazine, and ACNU as induction therapy. None underwent consolidation with whole-brain radiation therapy or high-dose chemotherapy with autologous stem cell transplantation. Clinical characteristics, survival outcomes, and treatment-related adverse events were evaluated.</p> Results <p>The overall response rate was 100%, with complete response in 65% of the patients. The 2- and 5-year progression-free survival (PFS) rates were 67.6% and 60.1%; the 5-year overall survival rate was 73.3%. Rituximab use was significantly associated with improved PFS (<i>p</i> = 0.03); cumulative HD-MTX dose and number of ACNU cycles were not. Hematologic toxicities (neutropenia or thrombocytopenia) occurred in 59% of the patients, and hepatic toxicities in 53%. One patient died of sepsis.</p> Conclusions <p>The MPA regimen yielded high response rates and durable disease control with acceptable toxicity in elderly PCNSL patients without consolidation. Rituximab use correlated with improved PFS. These findings support MPA, <i>particularly with rituximab</i>, as a promising frontline option for consolidation-ineligible patients and warrant prospective validation.</p>

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Induction chemotherapy with methotrexate, nimustine, and procarbazine for primary CNS lymphoma in the elderly: a retrospective evaluation of safety and efficacy

  • 期刊论文

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  • 发表日期：

    2026年1月20日

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  • Yoshihiro Umezawa,
  • Masahide Yamamoto,
  • Keisuke Tanaka,
  • Kota Yoshifuji,
  • Hiroki Akiyama,
  • Ayako Nogami,
  • Toshikage Nagao,
  • Takehiko Mori

摘要

Purpose

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma that predominantly affects elderly individuals. High-dose methotrexate (HD-MTX)-based chemotherapy remains the mainstay of PCNSL treatment, but the optimal combination regimen for elderly patients remains undefined. Nimustine (ACNU), a nitrosourea with excellent blood–brain barrier penetration, has not been evaluated in combination with HD-MTX. We investigated the efficacy and safety of HD-MTX combined with ACNU in elderly PCNSL patients.

Methods

We retrospectively analyzed the cases of 17 untreated PCNSL patients (median age, 71 years) who received the MPA regimen consisting of HD-MTX, procarbazine, and ACNU as induction therapy. None underwent consolidation with whole-brain radiation therapy or high-dose chemotherapy with autologous stem cell transplantation. Clinical characteristics, survival outcomes, and treatment-related adverse events were evaluated.

Results

The overall response rate was 100%, with complete response in 65% of the patients. The 2- and 5-year progression-free survival (PFS) rates were 67.6% and 60.1%; the 5-year overall survival rate was 73.3%. Rituximab use was significantly associated with improved PFS (p = 0.03); cumulative HD-MTX dose and number of ACNU cycles were not. Hematologic toxicities (neutropenia or thrombocytopenia) occurred in 59% of the patients, and hepatic toxicities in 53%. One patient died of sepsis.

Conclusions

The MPA regimen yielded high response rates and durable disease control with acceptable toxicity in elderly PCNSL patients without consolidation. Rituximab use correlated with improved PFS. These findings support MPA, particularly with rituximab, as a promising frontline option for consolidation-ineligible patients and warrant prospective validation.