{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:06:35Z","timestamp":1790265995348,"version":"4.1.0"},"reference-count":58,"publisher":"American Society of Hematology","issue":"13","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9,24]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>After 5 decades of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based therapy, the treatment landscape for patients with newly diagnosed large B-cell lymphoma (LBCL) is rapidly evolving. Novel agents, including antibody-drug conjugates, bispecific antibodies, targeted therapies, and chimeric antigen receptor T-cell therapies, have demonstrated significant activity, raising the potential for improved outcomes from first-line treatment. However, this progress has introduced substantial complexity without a clear framework for clinical decision-making. Ongoing phase 3 trials use heterogeneous designs, including differing control arms, eligibility criteria, and end points, yet share a common limitation: the inconsistent incorporation of biomarker-driven patient selection. As a result, cross-trial comparisons are challenging, and identifying the optimal regimen for an individual patient remains difficult. Although the POLARIX trial established polatuzumab-based therapy (R-CHP-pola) as superior to rituximab plus CHOP (R-CHOP), many ongoing studies continue to use R-CHOP as the comparator, further complicating interpretation. Moreover, \u201cR-CHOP + X\u201d strategies evaluated in clinically defined populations without biologic stratification may yield modest benefits across heterogeneous groups, limiting their applicability to individual patients. These trends risk producing a fragmented landscape of effective yet noncomparable regimens without a principled framework for patient selection. We thus propose a harmonized, data-driven strategy to shape the next era of LBCL therapy: (1) pooled patient-level analyses, (2) standardized biomarker and minimal residual disease platforms, (3) artificial intelligence\u2013enabled predictive modeling integrating trial and real-world data, and (4) regulatory approaches promoting collaborative trial design and shared biomarker analyses. Ultimately, progress in LBCL will depend on aligning data, biology, and clinical decision-making to deliver precise, equitable, and effective care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2026034393","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T17:24:56Z","timestamp":1783358696000},"page":"1651-1658","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["The chaos of choice in large B-cell lymphoma: a call to harmonize first-line trials"],"prefix":"10.1182","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1153-2294","authenticated-orcid":false,"given":"Dai","family":"Chihara","sequence":"first","affiliation":[{"name":"Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, 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