Fixed-Duration Pirtobrutinib Plus Venetoclax–Rituximab Versus Venetoclax–Rituximab for Patients with Previously Treated CLL/SLL: A Phase 3, Randomized Trial (BRUIN CLL-322)

Presenter: Matthew Davids

• This phase 3 trial compared fixed-duration pirtobrutinib–venetoclax–rituximab (PVR) versus venetoclax–rituximab (VR) in R/R CLL, including patients previously exposed to covalent BTKi.
• In 639 randomized patients, PVR significantly improved PFS (HR 0.547; 24‑month PFS 86.9% vs 71.8%) with consistent benefit across high-risk subgroups.
• Undetectable MRD rates were higher with PVR (86% vs 61%).
• Time to next treatment favoured PVR, while OS data remain immature.
• Safety profiles were comparable, with similar rates of grade ≥3 adverse events.
• BRUIN CLL-322 provides the first randomized phase 3 data for any BTKi as part of a fixed-duration regimen in R/R CLL, including in pts previously treated with cBTKi, and establishes fixed-duration PVR as a potential new SOC for R/R CLL.

First-in-Human Trial of LB2501, An in vivo CD19/CD20 Dual Targeting CAR-T Therapy, in Relapsed/Refractory B-Cell NHL

Presenter: Lei Fan

• This phase 1 study evaluated LB2501, an in vivo CD19/CD20 dual-targeting CAR-T lentiviral vector, in refractory/R B-cell NHL without lymphodepletion.
• Among 12 heavily pretreated patients, no dose-limiting toxicities, serious AE, or neurotoxicity were observed; CRS was mild (grade 1–2).
• At DL1, ORR was 50%, with 41.7% CR; at higher dose (DL2), ORR and CR rates reached 100% and 83.3%, respectively, with ongoing responses.
• PK showed dose-dependent CAR-T expansion and persistence up to 116 days.
• LB2501 demonstrated favorable safety, efficient in vivo T-cell transduction, and promising early efficacy, supporting further investigation as an “off-the-shelf” CAR-T therapy for B-cell malignancies.

Tafasitamab Plus Lenalidomide and R-CHOP for Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): Results from The Phase 3 FrontMIND Study

Presenter: Georg Lenz

• About 40% of DLBCL patients are not cured with first-line R‑CHOP, highlighting need for better regimens. The phase 3 frontMIND trial compared Tafa‑Len‑R‑CHOP vs R‑CHOP in high‑risk, untreated DLBCL patients.
• Among 899 participants, Tafa‑Len‑R‑CHOP significantly improved PFS (HR 0.75), with higher 24‑month PFS rates (71.1% vs 62.9%). Benefits were consistent across subgroups.
• EFS also improved by 21%, while overall survival data remain immature.
• Toxicities were higher but manageable, with similar discontinuation rates but fewer deaths in Tafa-Len-R-CHOP arm
• Overall, Tafa‑Len‑R‑CHOP shows meaningful efficacy and may become a new first‑line standard for high‑risk DLBCL/HGBL, regardless of COO molecular subtype.

Surovatamig (AZD0486) Plus Rituximab in Previously Untreated Follicular Lymphoma (FL): Initial Safety Data from The Phase 3 SOUNDTRACK-F1 Trial

Presenter: Chan Y. Cheah

• Surovatamig, a CD19xCD3 bispecific antibody, has shown high response rates in heavily pretreated FL.
• In the phase 3 SOUNDTRACK‑F1 safety run‑in, 43 untreated, high tumor burden FL patients received surovatamig plus rituximab.
• ORR were 95% and 100%, with CRR of 84% and 85% at DL1 and DL2 respectively.
• AE were common but manageable, mainly low‑grade cytokine release syndrome and infusion reactions, with no discontinuations or deaths. High MRD negativity was observed.
• Surovatamig in combination with rituximab showed deep responses and manageable safety and tolerability at both dose levels, with comparable TEAEs and no discontinuations. 
• Results support a 7.2 mg dose for ongoing phase 3 evaluation.

Outcomes of Venetoclax-Based Treatment in Patients with Bruton Tyrosine Kinase Inhibitor (BTKi)-Treated Chronic Lymphocytic Leukemia (CLL): An International Study Conducted by ERIC

Presenter: Thomas Chatzikonstantinou

• This large international retrospective study evaluated 624 CLL patients receiving venetoclax‑based therapy after prior BTKi treatment.
• Median time to next therapy or death (TTNTD) and OS were 33 and 46 months.
• Outcomes were significantly worse in patients who discontinued BTKi due to disease progression versus other reasons.
• Venetoclax plus obinutuzumab improved TTNTD compared with monotherapy, while TP53 disruption predicted poorer outcomes.
• Overall, results show inferior effectiveness of venetoclax post‑BTKi, especially in BTKi‑resistant disease, highlighting the need for improved and novel treatment strategies in this setting.

Venetoclax-Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia: Final Results of The Randomized CLL14 Study

Presenter: Kirsten Fischer

• The CLL14 trial evaluated 1‑year fixed‑duration venetoclax‑obinutuzumab (Ven‑Obi) versus chlorambucil‑obinutuzumab in previously untreated CLL with comorbidities.
• After ~9 years’ follow‑up, Ven‑Obi showed superior progression‑free survival (76.6 vs 37.9 months; HR=0.50) and longer TTNT (91.9 vs 52.5 months; HR=0.54).
• Benefits were reduced in patients with TP53 abnormalities or unmutated IGHV.
• Sustained MRD negativity was more frequent with Ven‑Obi. OS showed a favorable trend but was not statistically significant (HR=0.80).
• Second primary malignancies were slightly higher with Ven‑Obi. No further safety signals were observed.
• These results confirm durable long‑term efficacy of fixed‑duration Ven‑Obi in frontline CLL with mPFS > 6 yrs and mTTNT > 8 yrs.

FIGHT Trial: Fixed-Duration Ibrutinib Plus Obinutuzumab as First-Line Therapy for TP53-Intact Chronic Lymphocytic Leukemia (CLL)

Presenter: Emanuela Sant'Antonio

• Frontline CLL treatment is shifting toward fixed‑duration (FD) combinations to achieve deep responses and treatment‑free intervals.
• This phase 2 trial evaluated a 2‑year FD regimen of ibrutinib with delayed obinutuzumab in treatment‑naïve, TP53‑intact patients.
• After therapy, ORR was 84%, with 28% CR.
• Deep MRD negativity was achieved in 62% bone marrow and 70% peripheral blood.
• Safety was manageable with no new signals.
• At 30 months, mPFS was 75%.
• These results suggest that delayed obinutuzumab with FD ibrutinib produces durable, deep responses enabling safe treatment discontinuation in TN CLL patients.

Safety Data and Initial Pooled Efficacy Data from The Nordic Lymphoma Group Phase 3 Polar Bear Trial in Elderly or Frail Patients with Diffuse Large Cell Lymphoma - R-Pola-mini-CHP vs. R-mini-CHOP

Presenter: Mats Jerkeman.

• This phase 3 trial evaluated Pola‑R‑mini‑CHP versus R‑mini‑CHOP in elderly/frail patients with newly diagnosed DLBCL.
• Among 300 patients (median age 82), pooled outcomes showed encouraging efficacy, with 2‑year PFS of 67% and OS of 76%, regardless of age or comorbidity.
• Grade ≥3 AE were slightly higher with polatuzumab arm, including infections and gastrointestinal toxicity, though hematologic toxicity was similar between groups. Peripheral neuropathy was mostly mild. Fatal AE were more frequent in the polatuzumab arm.
• Overall, Rituximab/anthracycline‑based therapy remains standard of care for elderly and frail DLBCL patients, with manageable safety and improved outcomes compared to historical data.

Updated Efficacy and Safety Data from An Ongoing Phase 1A/B Trial of The BTK Degrader Bexobrutideg (NX-5948) in Patients with CLL Across Lines of Therapy

Presenter: Dr. Talha Munir.

• Bexobrutideg (NX‑5948), a novel BTK degrader, was evaluated in a phase 1A/B trial in 142 patients with CLL/SLL across different treatment settings.
• It showed a favorable safety profile, with mostly grade 1–2 AE.
• High ORR ~83–87% were observed across cohorts, including heavily pretreated, BTKi‑exposed, and treatment‑naïve patients.
• Responses occurred regardless of prior therapies, with reductions in lymph node size and durable benefit; mPFS was 22.1 months in phase 1a.
• These results support continued development and further evaluation (Ph2 DAYBreak-201 study and Ph3 DAYBreak-306) of bexobrutideg vs pirtobrutinib as a promising option for patients with BTKi‑resistant or earlier‑line CLL/SLL.

BTKi-First versus Venetoclax-Obinutuzumab-First Sequencing in CLL: A Propensity Score-Matched Total Disease Management Analysis

Presenter: Shankar Biwas.

• This large real‑world study compared treatment sequences in CLL: BTKi followed by venetoclax vs venetoclax‑obinutuzumab (VO) followed by BTKi.
• After propensity matching (1,776 patients per group), outcomes were similar across sequences.
• Mortality rates did not differ significantly (24.9% vs 26.7%), with comparable survival durations (median survival 2,823 versus 2,787 days). No differences were observed in atrial fibrillation, sepsis, hospitalizations, pancytopenia, or need for advanced therapies.
• Outcomes numerically favoured VO→BTKi, differences were not statistically significant.
• Overall, both sequencing strategies provide similar effectiveness and safety, supporting individualized treatment decisions based on patient characteristics until longer-term prospective data become available.

First-Line Treatment of CLL/SLL with the All-Oral Combination of Sonrotoclax and Zanubrutinib Achieves Undetectable Minimal Residual Disease Rates of >90%, Including in Patients with DEL(17P)/TP53

Presenter: Chan Y. Cheah

• A phase 1/1b study highlighted improved potency ~14x and differentiated profile of combination of zanubrutinib and sonrotoclax in treatment‑naive CLL/SLL.
• The study reports efficacy and safety of sonrotoclax and zanubrutinib combination in n=86 patients with median follow-up=30.9 months.
• ORR was 100%, with 55% CR and no disease progression (30‑month PFS 100%).
• Undetectable minimal residual disease (uMRD4) rates reached 99% overall and 100% in TP53/del(17p) patients, with rapid attainment (~3 months).
• No patient with uMRD4 reverted to MRD4+.
• In the next generation-sequencing set, best uMRD5 (<10^-5) was 86%.
• AE were tolerable: neutropenia (38%), contusion (38%), COVID-19 (33%); no adverse event-related deaths.
• Results indicated deep, durable responses and superior MRD clearance with the combination of zanubrutinib and sonrotoclax in treatment‑naive CLL/SLL.

Phase II Study of Lenalidomide Maintenance after Rituximab-Methotrexate-Based Induction Therapy in Primary CNS Lymphoma

Presenter: Ji Yun Lee

• This phase II multicenter study evaluated the efficacy and tolerability of lenalidomide maintenance in elderly patients with primary CNS lymphoma (PCNSL) and ineligible for consolidation after methotrexate–rituximab chemoimmunotherapy.
• n=30 patients received a median of 11 cycles, with 50% patients completing all 12 cycles.
• At 20.7 months’ follow-up, 2-yr PFS and OS rates were 58.8% and 83.9%, respectively.
• Grade 3–4 neutropenia was noted in 56% patients, while non-hematologic events were mostly mild.
• Treatment discontinuation due to toxicity occurred in 13%; one grade 5 pneumonia occurred.
• The study highlighted that lenalidomide maintenance after chemoimmunotherapy is feasible in elderly, consolidation-unsuitable PCNSL patients and warrants further investigation.

First-Line Obinutuzumab Plus Chemotherapy in Follicular Lymphoma: A Polish Research Lymphoma Group (PLRG) Real-World Study

Presenter: Ewa Paszkiewicz-Kozik

• A retrospective study evaluated real-world effectiveness of 1L obinutuzumab plus chemotherapy in 261 patients with advanced FL.
• After obinutuzumab with chemotherapy (O-CVP, O-CHOP, O-CVP-Doxo and O-Benda), responses were high (complete 74.3%, partial 20.9%) with no regimen differences (p=0.268).
• Most (86.8%) received obinutuzumab maintenance with median number of administered cycles of 11.
• After median 4.7 years, progression occurred in 17.6% and POD24 in 9%, with similar rates across regimens.
• Five‑year progression-free survival was 62% and overall survival (OS) 77%.
• Five-year OS for patients with vs without POD24 were comparable.
• However, mortality was impacted by COVID‑19 (37.5% deaths), highlighting the need for careful use of prolonged maintenance during viral outbreaks.
• The study indicated that obinutuzumab-based chemotherapy had  low risk of POD24 and low rate of progression consistent with results from GALLIUM trial.

Feasibility and Safety of Venetoclax–Obinutuzumab in Fit and Unfit Chronic Lymphocytic Leukemia Patients: Comparison of CLL13 and CLL14 Pooled Analysis With an Italian Clinical Practice Cohort

Presenter: Arianna Zappaterra

• This comparative analysis compared the feasibility and safety of fixed-duration venetoclax–obinutuzumab (VO) in clinical trials (CITr) versus clinical practice (CP) in 711 CLL patients.
• Treatment completion (86.6% in ClTr & 89.3% in CP) and discontinuation rates (8% ClTr vs. 10% CP pts) were similar.
• PFS CITr unfit – 88.7%, CITr fit – 92.8% and CP unfit – 87.7%, CP fit – 96.3% respectively
• OS CITr unfit – 92.5%, CITr fit – 99.4% and CP unfit – 89.2%, CP fit – 98.5% respectively
• TTNT CITr unfit – 95.9%, CITr fit – 97.8% and CP unfit – 97.7%, CP fit – 97.8% respectively
• Treatment free survival CITr unfit – 89.7%, CITr fit – 97.2% and CP unfit – 87.7%, CP fit – 96.3% respectively
• Higher rates of grade ≥3 AE (59.3%, 40.9% and 37.3% during early combination, combination and maintenance in ClTr vs. 38.4%, 21.2% and 14.7% in CP, resp.) and venetoclax dose reductions were reported; severe infections were comparable.
• Survival outcomes at 24 months were slightly favorable in CP.
• This analysis supported VO use as frontline treatment in routine clinical practice.

31^st European Hematology Association Congress (EHA 2026),11^th –14^th, 2026, Stockholm, Sweden.