2 0 2 6 C O M P E N D I U M O F F E D E R A L M E D I C I N E 9 3 has been the norm.6 The BOVen regimen produced an overall response rate (ORR) of 96%, with 88% of patients achieving complete response (CR). Undetectable minimal residual disease was documented in 95% of evaluable patients at cycle 13. With a median follow-up of 28.2 months, the two-year progression-free survival (PFS) was 72%, compared with the roughly 12-month median progression-free survival historically reported for chemoimmunotherapy in TP53- mutated MCL. Two-year overall survival was 76%, and disease-specific survival at two years was 91%, suggesting that the mortality signal in the short follow-up period was driven substantially by non-lymphoma causes, consistent with the older, multimorbid population enrolled. The NCCN has incorporated BOVen into its B-Cell lymphomas guidelines as a suitable option for all patients with TP53-mutated MCL, acknowledging the clinical rationale for a chemotherapy-sparing approach in a dis- ease subset that responds poorly to conventional therapy.7 For VA oncologists managing older veterans with TP53- mutated MCL, the BOVen regimen offers a fully outpa- tient, orally anchored treatment platform with response rates and overall survival that represent a meaningful advance over historical benchmarks. Follicular Lymphoma: A Category 2A Option in the Third Line and Beyond The most prevalent indolent B-cell lymphoma, follicu- lar lymphoma, has a characteristic relapsing-remitting course, which means that many patients accumulate multiple prior lines of therapy over years of disease man- agement. After progression through two or more prior systemic therapies that have included an anti-CD20 antibody and an alkylating agent, treatment options nar- row considerably, and the disease may exhibit increasing resistance to prior agents. The ROSEWOOD trial addressed this unmet need in a randomized, open-label, phase 2 study that enrolled 217 patients with relapsed or refractory grade 1 to 3A fol- licular lymphoma (FL) who had received at least two prior lines of therapy. Researchers randomized patients 2:1 to zanubrutinib plus the anti-CD20 monoclonal antibody obinutuzumab or obinutuzumab alone. The zanubrutinib- containing arm achieved an overall response rate of 69% compared with 46% in the control arm. The complete response rate was 39% vs. 19%. With a median follow- up of approximately 20 months, the median PFS was 28 months in the zanubrutinib plus obinutuzumab arm vs. 10.4 months in the control arm. Median time to next treatment was not reached in the combination arm vs. 12.2 months in the obinutuzumab alone arm.8 On the basis of ROSEWOOD, the FDA granted accel- erated approval to zanubrutinib plus obinutuzumab for patients with relapsed or refractory FL who had received at least two prior lines of systemic therapy in March 2024, making zanubrutinib the first and only BTK inhibitor approved in follicular lymphoma.9 The NCCN subse- quently incorporated the combination into its B-Cell Lymphomas guidelines as a category 2A recommended option for third-line and subsequent therapy in follicu- lar lymphoma, reflecting the randomized data and the absence of a clear single standard of care in this heavily pretreated setting. ROSEWOOD found cardiovascular events were con- sistent with other trials of zanubrutinib. The most com- mon adverse events were hematologic, primarily neu- tropenia and thrombocytopenia, and infusion-related reactions associated with obinutuzumab. For VA patients who have already progressed through standard chemoim- munotherapy in the first and second lines, the zanubru- tinib-obinutuzumab doublet offers a chemotherapy-free, outpatient regimen with favorable response rates and PFS duration. 1 Sgrignoli R, Rendo M, Fenderson JL, et al. Impact of military deploy- ment on non-Hodgkin lymphoma subtype. Meeting Abstract: 2024 ASCO Annual Meeting I. JCO. 2024 May 29;42(16 Suppl). E19070. 2 Tam CS, Opat S, D’Sa S, et al. A randomized phase 3 trial of zanubru- tinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood. 2020 Oct 29;136(18):2038-2050. doi: 10.1182/ blood.2020006844. PMID: 32731259; PMCID: PMC7596850. 3 Dimopoulos MA, Opat S, D’Sa S, et al. Zanubrutinib vs. ibrutinib in symptomatic Waldenström macroglobulinemia: final analysis from the randomized phase III ASPEN study. J Clin Oncol. 2023 Nov 20;41(33):5099-5106. doi: 10.1200/JCO.22.02830. Epub 2023 Jul 21. PMID: 37478390; PMCID: PMC10666987. 4 Dimopoulos MA, et al. Biomarker analysis of the ASPEN study compar- ing zanubrutinib with ibrutinib for patients with Waldenström macro- globulinemia. Blood Cancer J. 2024 Apr 9;8(7):1639-1650. doi: 10.1182/ bloodadvances.2023010906. PMID: 38315878; PMCID: PMC11006814. 5 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Waldenström Macroglobulinemia/Lymphoplas- macytic Lymphoma. Version 3.2025. https://www.nccn.org. 6 Kumar A, Soumerai J, Abramson JS, et al. Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutation. Blood. 2025 Jan 30;145(5):497-507. 7 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas. Version 2.2025. https:// www.nccn.org. 8 Zinzani PL, Mayer J, Flowers CR, et al. ROSEWOOD: A phase II randomized study of zanubrutinib plus obinutuzumab vs. obinutuzumab monotherapy in patients with relapsed or refractory follicular lym- phoma. J Clin Oncol. 2023 Nov 20;41(35):5107-5117. 9 U.S. Food and Drug Administration. FDA grants accelerated approval to zanubrutinib plus obinutuzumab for relapsed or refractory follicular lymphoma. March 7, 2024.
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