Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Health outcomes research, Clinical Research, Real-world evidence
Primary CNS lymphoma (PCNSL) is a rare and aggressive non-Hodgkin lymphoma with increasing incidence in the US particularly among elderly (PMID 26511214). Though initial response rates to regimens containing high-dose methotrexate (HD-MTX) can be upwards of 65%, 5 year overall survival (OS) is less than 30% (PMID 23873804). Aggressive consolidation strategies including whole brain radiation therapy (WBRT) and chemoimmunotherapy (CI) followed by autologous stem cell transplant (auto-SCT) can be toxic for older patients. Extended courses of HD-MTX are well tolerated and have favorable outcomes (PMID 36672475). Here we present our institutional experience.
Methods
We identified 156 patients with PCNSL from Jan 1, 1997 to Aug 30, 2023. Demographics, diagnostic work up, treatment and outcomes were reviewed retrospectively.
Results
156 patients with PCNSL were identified with a median follow up of 26.9 months (2-200 mo). 52.6% were female (82/156). 85.9% identified as non-Hispanic white (134/156), 7.0% Asian (11/156), 6.4% African-American (10/156) and 0.6% Hispanic (1/156). The median age at diagnosis was 63 with a range of 20 to 85 years. Most had an ECOG PS of between 0-1 (69.9%, 109/157) at diagnosis. The most common histology was DLBCL (91.0%, 142/156), then HGBCL (2.6%, 4/156), MZL (1.3%. 2/156), plasmablastic lymphoma (0.6%, 1/156) and PTCL (0.6%, 1/157). Non-germinal center B-cell (GCB) was the more common subtype in those with DLBCL (80.2%, 81/101) though we identified 20 cases of GCB PCNSL. 13 cases of DLBCL were EBV+ thought to be driven by immunodeficiency secondary to HIV (6.7%, 9/134), dermatomyositis or lupus.
In terms of treatment, 85.9% (135/156) were treated with a HD-MTX containing induction regimen. The most frequently used regimen was MTX-rituximab-temozolomide (MTR) in 83.0% of cases (112/135) based on CALBG 50202 then MTX-R (8.9%, 12/135), MTX alone (6.7%, 9/135), R-MTX-procarbazine-vincristine (0.7%, 1/135) and MTX-ibrutinib (0.7%, 1/135). Mean MTX dose was 5 g/m2 (2-8g/m2). Overall response rate to a HD-MTX induction regimen was 83.0% with 66.7% of patients in CR and 16.3% in PR.
Of the 135 patients who received HD-MTX based induction, 44.4% (60/135) received consolidation with MTX-based maintenance regimen, most receiving (91.7%, 55/60) MTR. The median number of cycles of HD-MTX was 6 (2-8 cycles). Those who did not receive MTX-based maintenance were treated with Rituximab-etoposide/ara-C (5.9%, 8/135), brain radiation (5.9%, 8/135), temozolomide maintenance (4.4%, 6/135), HD-chemotherapy followed by auto-SCT (3.0%, 4/136) or other treatments (ibrutinib, lenalidomide). 34.1% (46/135) of patients did not receive consolidation due to disease progression (52.2%, 24/46), patient preference (13.1%, 6/46), MTX toxicity (10.9%, 5/46), death (10.9%, 5/46) or they were lost to follow up.
57% (77/135) of patients undergoing MTX induction had no major adverse events (AE). The most common AEs were AKI (22.2%, 30/135) and transaminitis (8.1%, 11/135). 83.3% (25/30) of patients with AKIs required MTX dose reduction and less commonly discontinuation of the drug (36.7%, 11/30). Dose reduction due to transaminitis was required less frequently (7/11, 63.6%) as was drug discontinuation (1/11, 9.1%).
Among all patients, median OS was 11.6 mo (95% CI 6.5-18.5). 2 and 5 year OS rates were 62% and 45.5%, respectively. In patients who received at least 4 doses of HD-MTX induction without consolidation, median OS was 16.3 mo (95% CI 9.0-32.7). 2 and 5 year OS rates were 35.5% and 17.6%, respectively. In patients who completed HD-MTX induction and consolidation, median OS was 41.3 mo (95% CI 23.9-71.2). 2 and 5 year OS rates were 90.7% and 76.2% respectively. These data are comparable to reported survival outcomes after chemoimmunotherapy and auto-SCT. Cause of death included complications from lymphoma (72.7%, 64/88), unrelated solid tumor and pneumonia.
Conclusion
The majority of patients at our institution received HD-MTX induction followed by maintenance. In patients with response and who were able to tolerate treatment, long term remissions of >5 years were attainable. Though recent studies have shown improved survival in patients receiving HD-MTX based combination CI followed by auto-HSCT, non-relapse morbidity and mortality remain high, especially in the elderly population. These data show favorable outcomes with the use of MTX-based induction and consolidation.
Disclosures: Carter: Ispen: Honoraria. Tsai: Eli Lilly: Current holder of stock options in a privately-held company. Schuster: BeiGene: Consultancy, Honoraria; Kite Pharmaceuticals: Consultancy; Merck: Research Funding; Genentech/Roche: Consultancy, Honoraria, Research Funding; Celgene/Juno Therapeutics: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Acerta: Consultancy; Legend Biotech: Consultancy, Honoraria; BioNTech: Consultancy; Caribou Biosciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy; AstraZeneca: Consultancy, Honoraria; Genmab: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Nordic Nanovector: Honoraria, Membership on an entity's Board of Directors or advisory committees; viTToria biotherapeutics: Consultancy; Pharmacyclics: Consultancy, Research Funding. Svoboda: Seagen: Honoraria; Adaptive: Honoraria, Research Funding; Incyte: Research Funding; Atara: Honoraria; GenMab: Honoraria; Abbvie: Honoraria; TG Therapeutics: Honoraria; BMS: Honoraria; Merck: Honoraria. Chong: AstraZeneca: Consultancy, Research Funding; Nurix: Research Funding; CARGO: Research Funding; Genentech/Roche: Research Funding; AbbVie: Research Funding; Beigene: Consultancy; Genmab: Research Funding. Landsburg: ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Calithera: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GenMab: Honoraria. Nasta: ADCT: Membership on an entity's Board of Directors or advisory committees; GenMab: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Acrotech: Membership on an entity's Board of Directors or advisory committees; MERCK: Other: DSMB; Roche: Research Funding; Takeda: Research Funding; Loxo/Lilly: Research Funding; FortySeven/Gilead: Research Funding; ATAEA: Research Funding; ASTEX: Research Funding; ONO therapeutics: Research Funding; Caribou Biosciences: Research Funding.
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