The 2026 Society of Hematologic Oncology (SOHO) Annual Meeting featured several sessions focused on aggressive B-cell lymphoma (ABCL), including presentations exploring augmented frontline regimens, emerging genomic classifiers, and novel strategies for a patient population historically underserved by intensive chemoimmunotherapy. Together, these sessions contextualized where the treatment paradigm for diffuse large B-cell lymphoma (DLBCL) currently stands and where it is headed.
Here are some of the key takeaways from select ABCL sessions.
Tafa-Len-R-CHOP Significantly Improves PFS Over R-CHOP in High-Risk DLBCL and HGBL
Primary outcomes from the phase 3 frontMIND trial (NCT04824092) showed that adding tafasitamab (Monjuvi) and lenalidomide (Revlimid) to standard rituximab (Rituxan) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) produced a statistically significant improvement in progression-free survival (PFS) vs R-CHOP alone in patients with previously untreated high-risk DLBCL or high-grade B-cell lymphoma (HGBL).¹
Investigators randomly assigned 899 patients 1:1 to tafasitamab plus lenalidomide plus R-CHOP (Tafa-Len-R-CHOP; n = 448) or placebo plus R-CHOP (n = 451), with the experimental regimen reducing the risk of progression or death by 25% compared with R-CHOP (HR, 0.75; 95% CI, 0.59-0.96; P = .0194). The 2-year PFS rate was 71.1% with Tafa-Len-R-CHOP vs 62.9% with R-CHOP for an absolute difference of 8.2%, and the 3-year PFS rate was 67.3% vs 60.7%, respectively, for an absolute difference of 6.6%.1 In a post hoc analysis restricted to the centrally confirmed lymphoma subtype population (n = 773), the PFS benefit was more pronounced, with an HR of 0.68 (95% CI, 0.52-0.88; P = .0035) and a 2-year PFS difference of 10.5%.
An interim overall survival (OS) analysis demonstrated a positive trend (HR, 0.85; 95% CI, 0.63-1.14; P = .2703), with 2-year OS rates of 84.1% vs 80.5% and 3-year OS rates of 81.1% vs 77.8% with Tafa-Len-R-CHOP and R-CHOP, respectively.
Regarding safety, the most common grade 3 or higher treatment-emergent adverse effects (TEAEs) in the experimental arm were related to cytopenias, with neutropenia occurring in 70.7% of patients receiving Tafa-Len-R-CHOP vs 59.7% with R-CHOP. The rate of serious febrile neutropenia was 13.3% with Tafa-Len-R-CHOP vs 9.8% with R-CHOP. No new safety signals were identified, and incremental AEs did not impact delivery of the R-CHOP backbone.
An additional exploratory analysis showed that CD19 expression was maintained in 100% of patients in the Tafa-Len-R-CHOP arm with B-cell lymphoma detected at relapse, supporting the feasibility of subsequent CD19-directed therapy.
“The results support the use of Tafa-Len-R-CHOP as a potential new standard first-line treatment for patients with high-risk DLBCL or HGBL, regardless of cell of origin [COO] molecular subtype,” lead study presenter Jason Westin, MD, MS, FASCO, director of the Lymphoma Clinical Research Program, executive leader of the Lymphoma & Myeloma Service Line, and chief of Aggressive and Indolent Lymphoma at The University of Texas MD Anderson Cancer Center, concluded in the presentation.1
How Should Molecular Subtyping Inform Frontline Therapy Selection in DLBCL?
In an educational session, Brian Hill, MD, PhD, director of the Lymphoid Malignancies Program and associate professor of medicine at Cleveland Clinic Lerner College of Medicine, contextualized the expanding role of fluorescence in situ hybridization (FISH), gene expression profiling (GEP), and genomic classifiers in guiding frontline DLBCL treatment decisions.2
Hill reviewed how GEP categorizes DLBCL into 2 major COO subtypes, germinal center B-cell (GCB) and activated B-cell (ABC), and how advanced molecular techniques, including the LymphGen algorithm, can further subclassify DLBCL into at least 5 genomic clusters with distinct pathway dependencies, clinical outcomes, and therapeutic vulnerabilities. The MCD subtype, characterized by concurrent CD79B and MYD88L265P mutations, 18q gains, and BCL2 expression, was highlighted as a particularly high-risk entity among ABC-subtype cases, which is associated with poor prognosis even relative to other ABC DLBCL.
Hill also presented a comparative analysis of outcomes from pivotal frontline trials stratified by molecular subtype, illustrating that both polatuzumab vedotin (Polivy) plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-RCHP) and tafasitamab plus lenalidomide and R-CHOP significantly outperform R-CHOP alone. The PFS benefit for polatuzumab vedotin appeared primarily confined to the ABC subtype (HR, 0.34; 95% CI, 0.21-0.56) while tafasitamab’s benefit extended across molecular subtypes.
“R-CHOP is no longer associated with the best PFS in all patients,” Hill wrote in the presentation.2 “Future [first-line] trials, including those testing bispecific antibodies, should incorporate correlative studies to evaluate for preferential benefit of novel agents in specific DLBCL subtypes.”
How Do Bispecific Antibodies Fit Into the Older and Unfit DLBCL Treatment Landscape?
Pallawi Torka, MD, assistant attending physician at Memorial Sloan Kettering Cancer Center, presented a comprehensive overview of emerging treatment strategies for patients who are older and unfit with DLBCL, a population that represents a significant proportion of real-world cases but is routinely excluded or underrepresented in the major phase 3 trials.3
Torka emphasized that 5-year relative survival rates drop substantially with age, from 78.4% in patients younger than 55 years to 54.3% in those aged 65 and older, and that formal geriatric risk stratification tools, including the Fondazione Italiana Linfomi (FIL) Simplified Geriatric Assessment (sGA), can meaningfully guide fitness-adapted treatment decisions. In a 1163-patient cohort, the sGA classified 55% of patients as fit, 28% as unfit, and 18% as frail, with 3-year OS rates of 75%, 58%, and 43%, respectively.
For first-line patients who are unfit or frail, Torka reviewed emerging bispecific antibody data, highlighting particularly promising results with rituximab, polatuzumab vedotin, and glofitamab-gxbm (Columvi; R-Pola-Glo), which produced 1-year PFS and OS rates of 84.6% and 89.7%, respectively, while acknowledging that selection bias across these single-arm studies necessitates validation in randomized controlled trials. In the second-line setting, Torka reviewed outcomes from the phase 3 STARGLO trial (NCT04408638; glofitamab plus gemcitabine/oxaliplatin [GemOx]), phase 3 POLARGO trial (NCT04182204; polatuzumab vedotin plus rituximab and GemOx), and a phase 2 epcoritamab (Epkinly) plus GemOx cohort, each enrolling a significant proportion of patients aged 65 or older and demonstrating meaningful response rates and survival outcomes in this historically difficult-to-treat population.
“[Bispecific antibody] therapy may provide sustained benefit in patients otherwise destined for short-term palliation,” Torka wrote in the presentation.3 “CAR-T cell therapy is still the favored second-line option in most older patients with DLBCL,” she wrote, for those who are fit enough to tolerate the approach, though non-chemotherapy bispecific antibody combinations were identified as holding “the most promise for the future” in the second line setting or later. Torka also called for the development of non-CD19/CD20-dependent therapies to address the needs of patients who have exhausted current targets.
References
1. Westin JR, Lenz G, Trněný M, et al. Primary outcomes from the phase 3 study of tafasitamab plus lenalidomide and R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma (frontMIND). Presented at: 2026 Society of Hematologic Oncology (SOHO) Annual Meeting; September 9-12, 2026; Houston, TX. Abstract ABCL-489.
2. Hill BT. Selecting frontline therapy for DLBCL: the role of FISH, GEP, and genomic classifiers. Presented at: 2026 Society of Hematologic Oncology (SOHO) Annual Meeting; September 9-12, 2026; Houston, TX.
3. Torka P. Novel approaches to managing elderly and unfit patients with DLBCL. Presented at: 2026 Society of Hematologic Oncology (SOHO) Annual Meeting; September 9-12, 2026; Houston, TX.
