D. Baggio, S. Han, P. Ghione, I. Okcu, J. Okosun, M. Kamdar, A. Kuhnl, N. Grover, H. Cherng, A. Olszewski, P. Ramakrishnan Geethakumari, J. Smith, A. Prica, J. Khwaja, W. Osborne, J. Koff, D. El-Sharkawi, N. Wagner-Johnston, J. Munoz, A. Desai, N. Epperla, F. Baidoun, T. Moyo, M. Narkhede, A. Barrett, K. Linton, D. Wallace, N. Elmusharaf, J. Sandoval-Sus, A. Danilov, J. Rhodes, A. Santarsieri, F. Karim, J. Calabrese De Feo, R. Tavarozzi, I. Nizamuddin, N. Dong, A. Saha, W. Hann, Y. Wang, R. Treitman, A. Maraj, S. Tolu, T. Ollila, C. Abeyakoon, V. Calvert, A. Ayers, A. Hilali, I. Trutzer, S. Monick, J. Sharp, H. Tun, N. Ghosh, G. P. Collins, V. Deshani, J. Can, A. Kallam, B. Kahl, J. Chavez, K. Cwynarski, J. P. Alderuccio
{"title":"OUTCOMES IN AN INTERNATIONAL MULTICENTRE STUDY OF 600 PATIENTS WITH CNS RELAPSE OF LARGE B CELL LYMPHOMA: COMPARTMENT OF RELAPSE IS PROGNOSTIC","authors":"D. Baggio, S. Han, P. Ghione, I. Okcu, J. Okosun, M. Kamdar, A. Kuhnl, N. Grover, H. Cherng, A. Olszewski, P. Ramakrishnan Geethakumari, J. Smith, A. Prica, J. Khwaja, W. Osborne, J. Koff, D. El-Sharkawi, N. Wagner-Johnston, J. Munoz, A. Desai, N. Epperla, F. Baidoun, T. Moyo, M. Narkhede, A. Barrett, K. Linton, D. Wallace, N. Elmusharaf, J. Sandoval-Sus, A. Danilov, J. Rhodes, A. Santarsieri, F. Karim, J. Calabrese De Feo, R. Tavarozzi, I. Nizamuddin, N. Dong, A. Saha, W. Hann, Y. Wang, R. Treitman, A. Maraj, S. Tolu, T. Ollila, C. Abeyakoon, V. Calvert, A. Ayers, A. Hilali, I. Trutzer, S. Monick, J. Sharp, H. Tun, N. Ghosh, G. P. Collins, V. Deshani, J. Can, A. Kallam, B. Kahl, J. Chavez, K. Cwynarski, J. P. Alderuccio","doi":"10.1002/hon.70094_339","DOIUrl":null,"url":null,"abstract":"<p>D. Baggio, S. Han, K. Cwynarski, and J. P. Alderuccio equally contributing author.</p><p><b>Background</b>: Secondary central nervous system lymphoma (SCNSL) is a rare disease defined by involvement of the CNS concurrent to or following a diagnosis of systemic large B-cell lymphoma (LBCL). This international multicentre cohort study aimed to determine survival outcomes in patients (pts) with isolated CNS relapse (RI-SCNSL) and synchronous systemic/CNS relapse (RS-SCNSL).</p><p><b>Methods:</b> Pts ≥ 18 years treated 2001–2023 at 35 US, UK and Canadian centres were included. CNS involvement was categorised as: brain parenchyma, spine, leptomeninges, vitreoretinal, or > 1 compartment. The primary outcomes were time-to-CNS event from LBCL diagnosis, and progression-free and overall survival (PFS and OS) from time of CNS involvement.</p><p><b>Results:</b> Six hundred pts were included: 393 RI-SCNSL and 207 RS-SCNSL. Prior systemic LBCL treatment was RCHOP (450; 75%) or REPOCH (82; 14%) in the majority; median age at LBCL diagnosis was 62 (range 53–69); and CNS IPI was 4–6 in 139 (23%). Intrathecal and systemic methotrexate prophylaxis was delivered in 40 (10%) and 44 (11%) RI-SCNSL, and 29 (14%) and 33 (16%) RS-SCNSL respectively. Of RI-SCNSL, involvement of parenchyma (<i>n</i> = 257; 65%), leptomeninges (62; 16%), spine (14; 3.5%), vitreoretinal (11; 2.8%) and > 1 compartment (49; 2.5%) were observed. Of RS-SCNSL, these represented 77 (37%), 77 (37%), 15 (7.2%), 2 (1.0%) and 36 (17%), respectively.</p><p>Median time-to-CNS event was 10.3 months (range 6.6–25.6) for RI-SCNSL and 8 months (5.5–16.5) for RS-SCNSL (<i>p</i> = 0.0001). Median PFS and OS were superior for RI-SCNSL (14.7 and 22.6 months) compared to RS-SCNSL (6.8 and 8.2 months, <i>p</i> < 0.0001). Median time-to-CNS event was longer in both RI-SCNSL (<i>p</i> < 0.0001) and RS-SCNSL (<i>p</i> = 0.019) for parenchymal (13.1 and 10.9 months for RI and RS-SCNSL) and vitreoretinal disease (10.8 and 27.1 months for RI and RS-SCNSL) than leptomeningeal disease (6.9 months in both groups). In RI-SCNSL, CNS compartment was prognostic of PFS (<i>p</i> = 0.023), longest for vitreoretinal (median 117.4 months) and shortest for leptomeningeal disease (median 7.6 months). Outcomes were poor irrespective of CNS compartment in RS-SCNSL.</p><p>Comparing 139 patients with leptomeningeal to 257 with parenchymal involvement, leptomeningeal disease was enriched for <i>MYC/BCL2</i> double-hit status (20% versus 6.3% of parenchymal, <i>p</i> = 0.0002), ≥ 3 extranodal sites at LBCL diagnosis (17% versus 9.3%, <i>p</i> = 0.013), and bone marrow involvement (37% versus 17%, <i>p</i> < 0.0001). Conversely, isolated parenchymal involvement was enriched for a history of testicular LBCL (12% versus 3.6%, <i>p</i> = 0.017).</p><p><b>Conclusion:</b> Compartment of relapse holds prognostic significance in SCNSL. PFS and OS are significantly better for RI-SCNSL compared to RS-SCNSL. Isolated vitreoretinal relapse of LBCL carries a more favourable prognosis; however, RS-SCNSL outcomes are poor irrespective of CNS compartment involved. Further work is required to understand the biologic drivers of the clinical heterogeneity demonstrated amongst CNS relapses of LBCL.</p><p><b>Encore Abstract:</b> EHA 2025</p><p><b>Keywords:</b> aggressive B-cell non-Hodgkin lymphoma</p><p><b>Potential sources of conflict of interest:</b></p><p><b>P. Ghione</b></p><p><b>Consultant or advisory role:</b> Regeneron, Abbvie/Genmab</p><p><b>Honoraria:</b> Kite, Abbvie, ADC therapeutics, Ipsen Biopharmaceuticals</p><p><b>J. Okosun</b></p><p><b>Consultant or advisory role:</b> AstraZeneca, Genmab, Incyte</p><p><b>Honoraria:</b> AstraZeneca, BeiGene, Janssen</p><p><b>A. Kuhnl</b></p><p><b>Consultant or advisory role:</b> Kite/Gilead, Novartis, Abbvie, Sobi, Roche, BMS</p><p><b>Honoraria:</b> Kite/Gilead</p><p><b>Educational</b> <b>grants:</b> Kite/Gilead, AstraZeneca</p><p><b>N. Grover</b></p><p><b>Consultant or advisory role:</b> Novartis</p><p><b>Honoraria:</b> Genentech, Regeneron, ADC Therapeutics, BMS</p><p><b>H. Cherng</b></p><p><b>Honoraria:</b> ADC Therapeutics</p><p><b>A. Olszewski</b></p><p><b>Honoraria:</b> Genmab, Schrodinger, ADC Therapeutics, BeiGene, Bristol-Myers Squibb, Incyte</p><p><b>J. Koff</b></p><p><b>Honoraria:</b> AbbVie, Pierre Fabre, BeiGene</p><p><b>Other remuneration:</b> Viracta Therapeutics</p><p><b>J. Munoz</b></p><p><b>Consultant or advisory role:</b> Pharmacyclics/Abbvie, Bayer, Gilead/Kite, Beigene, Pfizer, Janssen, Celgene/BMS, Kyowa, Alexion, Fosunkite, Seattle Genetics, Karyopharm, Aurobindo, Verastem, Genmab, Genzyme, Genentech/Roche, ADC Therapeutics, Epizyme, Beigene, Novartis, Morphosys/Incyte, MEI, TG Therapeutics, AstraZeneca, Eli Lilly</p><p><b>Honoraria:</b> Targeted Oncology, OncView, Curio, Genzyme, and Physicians' Education Resource</p><p><b>Other remuneration:</b> Bayer, Gilead/Kite, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium, Novartis, Beigene</p><p><b>A. Barrett</b></p><p><b>Educational</b> <b>grants:</b> Ionis Pharmaceuticals, Abbvie, Roche, Karyopharm Therapeutics, Takeda</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":"43 S3","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.70094_339","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematological Oncology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hon.70094_339","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
D. Baggio, S. Han, K. Cwynarski, and J. P. Alderuccio equally contributing author.
Background: Secondary central nervous system lymphoma (SCNSL) is a rare disease defined by involvement of the CNS concurrent to or following a diagnosis of systemic large B-cell lymphoma (LBCL). This international multicentre cohort study aimed to determine survival outcomes in patients (pts) with isolated CNS relapse (RI-SCNSL) and synchronous systemic/CNS relapse (RS-SCNSL).
Methods: Pts ≥ 18 years treated 2001–2023 at 35 US, UK and Canadian centres were included. CNS involvement was categorised as: brain parenchyma, spine, leptomeninges, vitreoretinal, or > 1 compartment. The primary outcomes were time-to-CNS event from LBCL diagnosis, and progression-free and overall survival (PFS and OS) from time of CNS involvement.
Results: Six hundred pts were included: 393 RI-SCNSL and 207 RS-SCNSL. Prior systemic LBCL treatment was RCHOP (450; 75%) or REPOCH (82; 14%) in the majority; median age at LBCL diagnosis was 62 (range 53–69); and CNS IPI was 4–6 in 139 (23%). Intrathecal and systemic methotrexate prophylaxis was delivered in 40 (10%) and 44 (11%) RI-SCNSL, and 29 (14%) and 33 (16%) RS-SCNSL respectively. Of RI-SCNSL, involvement of parenchyma (n = 257; 65%), leptomeninges (62; 16%), spine (14; 3.5%), vitreoretinal (11; 2.8%) and > 1 compartment (49; 2.5%) were observed. Of RS-SCNSL, these represented 77 (37%), 77 (37%), 15 (7.2%), 2 (1.0%) and 36 (17%), respectively.
Median time-to-CNS event was 10.3 months (range 6.6–25.6) for RI-SCNSL and 8 months (5.5–16.5) for RS-SCNSL (p = 0.0001). Median PFS and OS were superior for RI-SCNSL (14.7 and 22.6 months) compared to RS-SCNSL (6.8 and 8.2 months, p < 0.0001). Median time-to-CNS event was longer in both RI-SCNSL (p < 0.0001) and RS-SCNSL (p = 0.019) for parenchymal (13.1 and 10.9 months for RI and RS-SCNSL) and vitreoretinal disease (10.8 and 27.1 months for RI and RS-SCNSL) than leptomeningeal disease (6.9 months in both groups). In RI-SCNSL, CNS compartment was prognostic of PFS (p = 0.023), longest for vitreoretinal (median 117.4 months) and shortest for leptomeningeal disease (median 7.6 months). Outcomes were poor irrespective of CNS compartment in RS-SCNSL.
Comparing 139 patients with leptomeningeal to 257 with parenchymal involvement, leptomeningeal disease was enriched for MYC/BCL2 double-hit status (20% versus 6.3% of parenchymal, p = 0.0002), ≥ 3 extranodal sites at LBCL diagnosis (17% versus 9.3%, p = 0.013), and bone marrow involvement (37% versus 17%, p < 0.0001). Conversely, isolated parenchymal involvement was enriched for a history of testicular LBCL (12% versus 3.6%, p = 0.017).
Conclusion: Compartment of relapse holds prognostic significance in SCNSL. PFS and OS are significantly better for RI-SCNSL compared to RS-SCNSL. Isolated vitreoretinal relapse of LBCL carries a more favourable prognosis; however, RS-SCNSL outcomes are poor irrespective of CNS compartment involved. Further work is required to understand the biologic drivers of the clinical heterogeneity demonstrated amongst CNS relapses of LBCL.
Encore Abstract: EHA 2025
Keywords: aggressive B-cell non-Hodgkin lymphoma
Potential sources of conflict of interest:
P. Ghione
Consultant or advisory role: Regeneron, Abbvie/Genmab
期刊介绍：
Hematological Oncology considers for publication articles dealing with experimental and clinical aspects of neoplastic diseases of the hemopoietic and lymphoid systems and relevant related matters. Translational studies applying basic science to clinical issues are particularly welcomed. Manuscripts dealing with the following areas are encouraged:
-Clinical practice and management of hematological neoplasia, including: acute and chronic leukemias, malignant lymphomas, myeloproliferative disorders
-Diagnostic investigations, including imaging and laboratory assays
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-Therapeutic issues including Phase 1, 2 or 3 trials as well as allogeneic and autologous stem cell transplantation studies
-Aspects of the cell biology, molecular biology, molecular genetics and cytogenetics of normal or diseased hematopoeisis and lymphopoiesis, including stem cells and cytokines and other regulatory systems.
Concise, topical review material is welcomed, especially if it makes new concepts and ideas accessible to a wider community. Proposals for review material may be discussed with the Editor-in-Chief. Collections of case material and case reports will be considered only if they have broader scientific or clinical relevance.
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