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Multicenter Study
. 2024 Oct 22;8(20):5355-5364.
doi: 10.1182/bloodadvances.2024013791.

High-grade B-cell lymphoma, not otherwise specified: CNS involvement and outcomes in a multi-institutional series

Narendranath Epperla  1   2 , Adam S Zayac  3 , Daniel J Landsburg  4 , Allison M Bock  2   5 , Grzegorz S Nowakowski  5 , Emily C Ayers  6 , Mark Girton  7 , Marie Hu  8 , Amy Beckman  9 , Shaoying Li  10 , L Jeffrey Medeiros  10 , Julie E Chang  11 , Habibe Kurt  12 , Jose Sandoval-Sus  13 , Mohammad Ali Ansari-Lari  14 , Shalin K Kothari  15 , Anna Kress  15 , Mina L Xu  16 , Pallawi Torka  17 , Suchitra Sundaram  17 , Stephen D Smith  18   19 , Kikkeri N Naresh  20   21 , Yasmin Karimi  22 , David A Bond  1 , Andrew M Evens  23 , Seema G Naik  24 , Manali Kamdar  25 , Bradley M Haverkos  25 , Reem Karmali  26 , Umar Farooq  27 , Julie M Vose  28 , Paul Rubinstein  29 , Amina Chaudhry  29 , Adam J Olszewski  3
Affiliations
Multicenter Study

High-grade B-cell lymphoma, not otherwise specified: CNS involvement and outcomes in a multi-institutional series

Narendranath Epperla et al. Blood Adv. .

Abstract

Little is known about the central nervous system (CNS) risk in high-grade B-cell lymphoma, not otherwise specified (HGBL NOS). Hence, we sought to describe the rates of baseline CNS involvement, risk of CNS recurrence after primary therapy, and management strategies in HGBL NOS. In this multicenter retrospective study, we included 160 adults with newly diagnosed HGBL NOS treated between 2016 and 2021 at 20 US institutions. Eleven patients (7%) had baseline CNS involvement at diagnosis (leptomeningeal = 6, parenchymal = 4, and both = 1). Baseline CNS involvement was significantly associated only with MYC rearrangement (OR = 3.5) and testicular (in men) or female pelvic (in women) involvement (OR = 8.1). There was no significant difference in survival outcomes between patients with HGBL NOS with (median PFS = 4 years) or without (median PFS = 2.4 years) baseline CNS involvement (P = 0.45). The cumulative incidence of CNS recurrence at 3 years was 11%. Patients with baseline CNS involvement were at the highest risk (48.5% vs 8% for those without baseline CNS involvement) and were excluded from the risk factors analysis for CNS recurrence. The risk for CNS recurrence was significantly associated with blood or bone marrow involvement, CD5 expression, non-germinal center B-cell subtype, and "dual-expresser lymphoma" phenotype, however, high CNS IPI was not. The prognosis of relapsed HGBL NOS was poor, regardless of whether recurrence was systemic or limited to the CNS, and with currently available salvage strategies, including autologous transplantation and chimeric antigen receptor T-cell modalities, almost all patients with CNS recurrence ultimately succumbed to their disease.

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Conflict of interest statement

Conflict-of-interest disclosure: N.E. reports research funding from BeiGene and Eli Lilly; serves on the speaker's bureau for BeiGene and Genentech; serves on advisory boards for Ipsen, Lilly, and ADC Therapeutics; and reports consultancy for Novartis. R.K. serves in a consultant role for Bristol Myers Squibb, Janssen, MorphoSys/Incyte, Epizyme, Genentech/Roche, GenMab, Lilly Oncology, AbbVie, and Miltenyi; reports grants/research support from Bristol Myers Squibb, Takeda, BeiGene, Gilead Sciences/Kite, and Miltenyi; and serves on the speakers' bureau for AstraZeneca, BeiGene, and Incyte. P.T. reports honoraria, consulting roles, and advisory board membership for TG Therapeutics, ADC Therapeutics, Genentech, GenMab, Seagen, AbbVie, and Lilly USA. A.J.O. reports research funding from Genmab, Precision Bio, Adaptive Biotechnologies, Celldex, Acrotech Biopharma, Schrodinger, TG Therapeutics, and Genentech. M.L.X. reports consulting roles for Pure Marrow and Treeline Biosciences. D.A.B. reports consulting roles for Novartis, Nurix Therapeutics, and ADC Therapeutics, and and received research funding from Novartis, Nurix Therapeutics, Incyte, Kite/Gilead, Bristol Myers Squibb, Genmab, and Accutar Biotechnology. A.M.B. reports honoraria and advisory board membership for AbbVie. M.K. reports research support/funding from Novartis; consultancy with AbbVie, AstraZeneca, Celgene/Bristol Myers Squibb, BeiGene, and Genentech; and serves on the speakers' bureau of Seagen, Celgene, and Genentech. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
PFS and OS in patients with HGBL NOS based on the presence of absence of baseline CNS involvement. (A) PFS and (B) OS. P values are from log-rank test.
Figure 2.
Figure 2.
Cumulative incidence of CNS recurrence in patients with HGBL, NOS. (A) In all patients and (B) stratified by presence or absence of CNS involvement. P values are from a Gray test.
Figure 3.
Figure 3.
Factors associated with the risk of CNS recurrence. This is based on univariate Fine-Gray regression models. The size of the circles is proportional to the prevalence of the risk factor among patients with CNS recurrence.
Figure 4.
Figure 4.
Risk of CNS recurrence in patients with HGBL, NOS based on blood or bone marrow involvement, CD5 expression, COO, and DEL phenotype and CNS-IPI. (A) Blood involvement; (B) bone marrow involvement; (C) CD5 expression; (D) non-GCB COO; (E) DEL phenotype; and (F) CNS-IPI. P values are from Gray’s test.
See this image and copyright information in PMC

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