Safety and efficacy of induction immunochemotherapy with rituximab, methotrexate, ifosfamide, and vincristine (R-MIV) in patients with primary CNS lymphoma including recent COVID-19 pandemic experience

Br J Haematol. 2023 May;201(4):663-672. doi: 10.1111/bjh.18687. Epub 2023 Feb 10.

Abstract

Clinical data on primary central nervous system (CNS) lymphoma (PCNSL) patients is mostly generated from prospective studies, and many frail real-world patients are not included. Recently,the diagnosis and treatment of PCNSL patients was confounded by the COVID-19 pandemic. In particular, treatment with high-dose cytarabine was linked to increased risk of pneumonia and virus persistence. We report on outcome of the induction regimen R-MIV (rituximab, methotrexate, ifosfamide, and vincristine) involving intensive administration of high-dose methotrexate (3.5 g/m2 ) with ifosfamide, every 2 weeks and rituximab once per week for six doses. The median age and performance status (PS) for 64 patients was 58 years and 2 (PS 3; 22%) respectively. The overall response rate by magnetic resonance imaging/computed tomography (MRI/CT) was 73% (n = 46/63), with an additional 17.5% (n = 11/63) patients without measurable disease at baseline. Grade 3-4 haematological toxicity was low for R-MIV (neutropenia: 25% and thrombocytopenia: 1%). Three patients (4.7%) died from treatment-related toxicity. Co-existence of SARS-CoV-2 infection with cytomegalovirus reactivation and the varicella-zoster virus in two patients was fatal. Fifty patients (78%) were eligible for consolidation. Median progression-free and overall survival were not reached (median follow-up: 44 months). In conclusion, the R-MIV regimen is feasible in routine practice, effective and safe, even during the COVID-19 pandemic.

Keywords: COVID-19; HD-MTX; PCNSL, primary CNS lymphoma; remission induction.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • COVID-19* / etiology
  • Central Nervous System Neoplasms* / drug therapy
  • Cytarabine / therapeutic use
  • Humans
  • Ifosfamide / adverse effects
  • Lymphoma* / etiology
  • Methotrexate / adverse effects
  • Pandemics
  • Prospective Studies
  • Rituximab / adverse effects
  • SARS-CoV-2
  • Vincristine / adverse effects

Substances

  • Methotrexate
  • Rituximab
  • Ifosfamide
  • Vincristine
  • Cytarabine