include five-year results from the phase III CLL14 study of fixed-duration Venclexta ® /Venclyxto ® (venetoclax) plus Gazyva ® /Gazyvaro ® (obinutuzumab) in previously untreated chronic lymphocytic leukaemia (CLL); the final analysis of the phase III GALLIUM study of Gazyva/Gazyvaro plus chemotherapy in people with previously untreated advanced-stage follicular lymphoma (FL); and subanalyses from the phase III POLARIX study of Polivy ® (polatuzumab vedotin) in combination with MabThera After a median of 65.4 months following treatment with Venclexta/Venclyxto plus Gazyva/Gazyvaro, results confirm the combination continues to be an effective fixed-duration and chemotherapy-free option for patients with previously untreated CLL and coexisting conditions. The estimated investigator-assessed progression-free survival (PFS) rate at this follow-up was 62.6% with Venclexta/Venclyxto plus Gazyva/Gazyvaro and 27.0% with Gazyva/Gazyvaro plus chlorambucil, and the estimated overall survival (OS) rate was 81.9% versus 77.0% (HR 0.72; 95% CI: 0.48-1.09; p=0.12). In addition, the analysis found that 72.1% of patients in the Venclexta/Venclyxto plus Gazyva/Gazyvaro arm did not require another treatment for CLL in the five years following initial treatment (HR 0.42; 95% CI: 0.31-0.57; p<0.0001). No new safety signals were observed.[1] The CLL14 study is being conducted in cooperation with the German CLL Study Group, headed by Michael Hallek, M.D., University of Cologne. phase After eight of follow-up in with previously untreated FL, a meaningful in PFS with Gazyva/Gazyvaro plus its a standard first-line Seven-year investigator-assessed PFS significantly improved with Gazyva/Gazyvaro plus chemotherapy (63.4%) compared with on the positive POLARIX results from the overall study population, the European Commission (EC) approved Polivy plus R-CHP in May 2022 for the treatment of adult patients DLBCL. Pivotal phase The pivotal phase II NP30179 expansion study included patients with heavily pre-treated and highly refractory DLBCL and showed fixed-duration glofitamab, an investigational CD20xCD3 T-cell engaging bispecific antibody, induced high and durable complete response (CR) rates. After a median follow-up of 12.6 months, 39.4% of patients (n=61/155) achieved a CR (primary efficacy endpoint) and half of them (51.6%; n=80/155) achieved an overall response (the percentage of patients with a partial or CR; secondary efficacy endpoint), as assessed by an independent review committee. Cytokine release syndrome (CRS) was the most common adverse event, occurring in 63.0% of patients.[4] These data were recently presented at the American Society of Clinical Oncology 2022 Annual Meeting and have been submitted for approval to the European Medicines Agency (EMA). Submissions to additional health authorities worldwide, including the U.S. Food and Drug Administration (FDA), are planned this year. and patients aged <65 and ≥65 years who had R/R prior a higher objective response rate (ORR) than those <65 years old (87.0% 77.0%, respectively). Lower rates CRS and

Roche announces positive data from broad blood cancer portfolio at European Hematology Association Annual Meeting

7558 Background: In the pivotal Phase III POLARIX trial, Pola-R-CHP demonstrated significantly improved progression-free survival (PFS) compared with R-CHOP, with a similar safety profile in patients with previously untreated DLBCL (Tilly et al. 2022). An Asia subpopulation analysis was included as part of the trial design; patients enrolled in Asia were analyzed for the purpose of registration in China of POLARIX (NCT03274492). Methods: Patients from mainland China, Hong Kong, Japan, South Korea, and Taiwan (enrolled during the global phase), and from the China extension cohort were included in the Asia subpopulation. POLARIX methods were previously described (Tilly et al. 2022). Briefly, patients with untreated DLBCL were randomized 1:1 using the same stratification factors to receive six cycles of Pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The purpose of this analysis was to evaluate consistency of PFS (defined as ≥50% risk reduction in PFS) in the Asia subpopulation with the global population. Results: Overall, 281 patients (intent-to-treat population; 150, 85, 31 and 15 patients in mainland China, Japan, South Korea and Taiwan, respectively) were analyzed (141 received Pola-R-CHP and 140 received R-CHOP); 160 patients from the global population and 121 from the China extension cohort. Median age was 63 (range 19–79) years, and most patients had an International Prognostic Index of 3–5 (61.9%). At the data cut-off of June 28, 2021, (median follow-up of 24.2 months) PFS was superior with Pola-R-CHP vs R-CHOP (hazard ratio [HR] 0.64; 95% confidence interval [CI]: 0.40–1.03) and met the consistency definition with the global population. The 2-year PFS rate was 74.2% (95% CI: 65.7–82.7) with Pola-R-CHP vs 66.5% (95% CI: 57.3–75.6) with R-CHOP. Other key efficacy results were similar to the global study results (Table). The safety profile was generally comparable for Pola-R-CHP vs R-CHOP, including rates of grade 3–4 adverse events (AEs; 72.9% vs 66.2%), serious AEs (32.9% vs 32.4%), grade 5 AEs (1.4% vs 0.7%), AEs leading to discontinuation of any study treatment (5.0% vs 7.2%), and incidence of peripheral neuropathy (all grades, 44.3% vs 50.4%), respectively. Key efficacy results. CR, complete response. Conclusions: The results from the Asia subpopulation of POLARIX were consistent with the global study, with a clinically meaningful improvement in PFS (risk of disease progression, relapse or death reduced by 36%) following treatment with Pola-R-CHP vs R-CHOP, and a comparable safety profile in Asian patients with previously untreated DLBCL. Clinical trial information: NCT03274492. [Table: see text]

https://doi.org/10.1097/01.hs9.0000847632.22579.29

P1192: asia subpopulation analysis from the phase iii polarix trial

Orelabrutinib‐lenalidomide‐rituximab (olr) in patients with untreated mantle cell lymphoma (mcl): a prospective, multicenter, single‐arm phase 2 polaris study in china

Objective: To explore the clinical features and survival of newly diagnosed follicular lymphoma (FL) patients with diffuse large B-cell lymphoma (DLBCL) component. Methods: 1845 newly diagnosed FL patients aged ≥ 18 years with grades 1-3a in 11 medical centers in China from 2000 to 2020 were included, and patients with DLBCL component were screened. The clinical data and survival data of the patients were retrospectively analyzed, and the prognostic factors were screened by univariate and multivariate analysis. Results: 146 patients (7.9% ) with newly diagnosed FL had DLBCL component. The median age was 56 (25-83) years, 79 males (54.1% ) . The pathology of 127 patients showed the proportion of DLBCL component. Patients were divided into two groups according to whether the proportion of DLBCL component was ≥ 50% . The study found that patients with DLBCL component ≥ 50% had higher grade 3 ratio (94.3% vs 91.9% , P=0.010) , Ki-67 index ≥ 70% ratio (58.5% vs 32.9% , P=0.013) and PET-CT SUVmax ≥ 13 ratio (72.4% vs 46.3% , P=0.030) than patients with DLBCL component<50% . All patients received CHOP or CHOP like ± rituximab chemotherapy. The overall response rate (ORR) was 88.2% , and the complete response (CR) rate was 76.4% . In the groups with different proportions of DLBCL component, there was no significant difference in the remission rate after induction treatment and the incidence of disease progression within 2 years after initiation of treatment (POD24) (P<0.05) . The overall estimated 5-year progression free survival (PFS) rate was 58.9% , and the 5-year overall survival (OS) rate was 90.4% . The 5-year OS rate of POD24 patients was lower than that of non POD24 patients (70.3% vs 98.5% , P<0.001) . Compared with non maintenance treatment of rituximab, maintenance treatment of rituximab could not benefit the 5-year PFS rate (57.7% vs 58.8% , P=0.543) , and the 5-year OS rate had a benefit trend, but the difference was not statistically significant (100% vs 87.8% , P=0.082) . Multivariate analysis showed that failure to reach CR after induction treatment was an independent risk factor for PFS (P=0.006) , while LDH higher than normal was an independent risk factor for OS (P=0.031) . Conclusion: FL patients with DLBCL component ≥50% have more invasive clinical and pathological features. CHOP/CHOP like ± rituximab regimen can improve the clinical efficacy of patients. Rituximab maintenance therapy can not benefit the PFS and OS of patients. Failure to reach CR after induction therapy was the independent unfavorable factor for PFS.

[Clinical features and outcomes of newly diagnosed follicular lymphoma concurrent with diffuse large B-cell lymphoma component].

Introduction: Zanubrutinib is an irreversible, potent, next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target inhibition. In a randomized phase 3 study (ALPINE; NCT03734016), zanubrutinib was compared head to head with ibrutinib as a treatment for R/R CLL (including small lymphocytic lymphoma [SLL]). In the predefined progression-free survival (PFS) final analysis, zanubrutinib demonstrated superior efficacy and a favorable safety profile versus ibrutinib (Brown et al. NEJM 2022). Data from the prespecified subgroup in pts from China are reported here. Methods: Patients (pts) with R/R CLL/SLL who had received ≥1 prior line of therapy and had measurable disease by imaging were randomized (1:1) to receive zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily, until disease progression or unacceptable toxicity. Randomization included stratification by geographical region (China vs. non-China). Data from the subgroup in pts from China were descriptively analyzed. Results: A total of 90 pts in China with R/R CLL/SLL (zanubrutinib, n = 47; ibrutinib, n = 43) were enrolled. Disease characteristics and baseline demographics were balanced between zanubrutinib and ibrutinib (aged ≥65 y [40% vs. 37%]; unmutated IGHV [59.6% vs. 62.8%]; del17p/TP53 mutated [34.0% vs. 32.6%]) with a median age of 60 and 61 y, respectively. Median number of prior therapies was 1. At a median follow-up of 25.3 mo, PFS by independent review committee (IRC) was improved with zanubrutinib versus ibrutinib (hazard ratio [HR]: 0.24; 95% CI 0.09-0.64; nominal 2-sided P = 0.002) with 18-mo landmark PFS rates of 88.9% versus 71.6% for zanubrutinib and ibrutinib, respectively (Figure). Additionally, zanubrutinib was more favorable in high-risk del17p/TP53 mutation (18-mo landmark 80.0% vs. 64.3%; HR: 0.51; 95% CI 0.12-2.13). ORR also favored zanubrutinib over ibrutinib (87.2% vs. 76.7%; 95% CI 0.93-1.38) by IRC. The treatment discontinuation rate was lower with zanubrutinib (14.9%) versus ibrutinib (41.9%) with most due to progressive disease (6.4% vs. 20.9%) and adverse events (AEs; 6.4% vs. 14.0%). Rates of grade ≥3 AEs (64.4% vs. 72.1%) and serious AEs (35.6% vs. 51.2%) were lower with zanubrutinib versus ibrutinib. With zanubrutinib, 4 deaths (8.5%) were reported compared to 8 deaths (18.6%) with ibrutinib (HR: 0.45; 95% CI 0.14–1.50). Keywords: Chronic Lymphocytic Leukemia (CLL), Molecular Targeted Therapies Conflicts of interests pertinent to the abstract L. Fu Employment or leadership position: BeiGene Stock ownership: BeiGene T. Salmi Employment or leadership position: BeiGene Stock ownership: BeiGene K. Wu Employment or leadership position: BeiGene Stock ownership: BeiGene L. Wang Employment or leadership position: BeiGene Stock ownership: BeiGene J. R. Brown Consultant or advisory role AbbVie, Acerta/AstraZeneca, BeiGene, Genentech/Roche, Grifols Worldwide Operations, Hutchmed, iOnctura, Janssen, Kite, Loxo/Lilly, MEI Pharma, Numab Therapeutics, Pfizer, Pharmacyclics Research funding: BeiGene, Gilead, iOnctura, Loxo/Lilly, MEI Pharma, TG Therapeutics 

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hon.3165_592

Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (r/r cll) in china: a subgroup of alpine

Background: R-CHOP immunochemotherapy is the first-line treatment for DLBCL, but approximately 30%–40% of patients still experience refractory or relapsed (R/R) disease. We aimed to characterize the molecular features of DLBCL derived from patients with early R/R disease and develop a prognosis model to identify those high-risk patients. Methods: We performed a comprehensive genomic and transcriptomic characterization on 161 R-CHOP-treated DLBCL samples. These patients were grouped by follow-up outcome status after R-CHOP treatment. The first group had R/R disease within two years of diagnosis (poor outcome; n = 50), and the second group remained in remission at two years following R-CHOP treatment (good outcome; n = 111). In an addition, external cohorts were included in the validation analysis (GSE117556, n = 374; GSE181063, n = 810). Results: Patients with poor outcomes more often had an advanced stage of the disease, a high international prognostic index (IPI) and a non-GCB subtype of the tumor. We identified a set of frequent somatically mutated targets (Figure 1A), including PIM1, TP53, MPEG1 and ROBO1, as well as a specific mutational signature (activation-induced cytidine deaminase related) in DLBCLs with poor outcomes. Transcriptomic analyses further showed a distinct gene expression pattern and a less inflamed tumor microenvironment in these patients (Figure 1B). Finally, we developed an 11-gene signature as an independent prognostic marker for DLBCL patients treated with R-CHOP (Figure 1C). The 11-gene signature could further stratify DLBCL patients based on their IPI scores (Figure 1D). Additionally, the use of 11-gene signature to identify high-risk patients was also validated in two independent cohorts, suggesting the robustness of the risk model. Furthermore, our model effectively identified high-risk patients, including those with double-hit and MCD genetic subtypes that are associated with poor survival outcomes. FIGURE 1 (A) The mutation pattern between poor outcome and good outcome DLBCLs. (B) Tumor-infiltrating immune cells in DLBCL patients with poor and good outcomes. (C-D) Kaplan–Meier survival analysis of PFS between high-risk and low-risk groups (C) and the association of 11-gene risk scores and IPI risk groups (D). Keywords: Aggressive B-cell non-Hodgkin lymphoma, Diagnostic and Prognostic Biomarkers, Genomics, Epigenomics, and Other -Omics No conflicts of interests pertinent to the abstract. 

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hon.3164_211

H. Zhang

Papers

P1192: asia subpopulation analysis from the phase iii polarix trial

Orelabrutinib‐lenalidomide‐rituximab (olr) in patients with untreated mantle cell lymphoma (mcl): a prospective, multicenter, single‐arm phase 2 polaris study in china

[Clinical features and outcomes of newly diagnosed follicular lymphoma concurrent with diffuse large B-cell lymphoma component].

Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (r/r cll) in china: a subgroup of alpine

Genetic and transcriptomic analyses of diffuse large B‐cell lymphoma patients with poor outcomes within two years of diagnosis