Key clinical point: Orelabrutinib showed considerable efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 23.8 months, the overall response rate was 81.1%, with 27.4% and 53.8% of patients achieving complete and partial responses, respectively. The median duration of response and progression-free survival were 22.9 (95% CI 16.4-not reached) and 22.0 (95% CI 13.8-not reached) months, respectively. The median overall survival was not reached. Most adverse events (AE) were grade 1 or 2. Grade ≥3 AE were infrequent, with thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%) being the most common.

Study details: This multicenter phase 1/2 study included adult patients with MCL who had relapsed after or were refractory to ≥1 and ≤4 prior therapies and received 150 mg oral orelabrutinib once daily (n = 86) or 100 mg twice daily (n = 20).

Disclosures: This study was sponsored by InnoCare Pharma Limited, China. Four authors declared being employees of InnoCare. The other authors declared no financial conflicts of interest.

Source: Deng LJ et al. Orelabrutinib for the treatment of relapsed or refractory MCL: A phase 1/2, open-label, multicenter, single-arm study. Blood Adv. 2023 (Apr 20). Doi: 10.1182/bloodadvances.2022009168

Key clinical point: Orelabrutinib showed considerable efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 23.8 months, the overall response rate was 81.1%, with 27.4% and 53.8% of patients achieving complete and partial responses, respectively. The median duration of response and progression-free survival were 22.9 (95% CI 16.4-not reached) and 22.0 (95% CI 13.8-not reached) months, respectively. The median overall survival was not reached. Most adverse events (AE) were grade 1 or 2. Grade ≥3 AE were infrequent, with thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%) being the most common.

Study details: This multicenter phase 1/2 study included adult patients with MCL who had relapsed after or were refractory to ≥1 and ≤4 prior therapies and received 150 mg oral orelabrutinib once daily (n = 86) or 100 mg twice daily (n = 20).

Disclosures: This study was sponsored by InnoCare Pharma Limited, China. Four authors declared being employees of InnoCare. The other authors declared no financial conflicts of interest.

Source: Deng LJ et al. Orelabrutinib for the treatment of relapsed or refractory MCL: A phase 1/2, open-label, multicenter, single-arm study. Blood Adv. 2023 (Apr 20). Doi: 10.1182/bloodadvances.2022009168

Key clinical point: Orelabrutinib showed considerable efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 23.8 months, the overall response rate was 81.1%, with 27.4% and 53.8% of patients achieving complete and partial responses, respectively. The median duration of response and progression-free survival were 22.9 (95% CI 16.4-not reached) and 22.0 (95% CI 13.8-not reached) months, respectively. The median overall survival was not reached. Most adverse events (AE) were grade 1 or 2. Grade ≥3 AE were infrequent, with thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%) being the most common.

Study details: This multicenter phase 1/2 study included adult patients with MCL who had relapsed after or were refractory to ≥1 and ≤4 prior therapies and received 150 mg oral orelabrutinib once daily (n = 86) or 100 mg twice daily (n = 20).

Disclosures: This study was sponsored by InnoCare Pharma Limited, China. Four authors declared being employees of InnoCare. The other authors declared no financial conflicts of interest.

Source: Deng LJ et al. Orelabrutinib for the treatment of relapsed or refractory MCL: A phase 1/2, open-label, multicenter, single-arm study. Blood Adv. 2023 (Apr 20). Doi: 10.1182/bloodadvances.2022009168

Key clinical point: First-line autologous stem cell transplantation (ASCT) resulted in long-term clinical and molecular remissions in patients with disseminated mantle cell lymphoma (MCL).

Major finding: The 10-year overall survival, progression-free survival, and freedom from progression rates for the first-line vs second-line cohort were 64%, 52%, and 59% vs 50%, 20%, and 20%, respectively. Overall, 27 patients experienced sustained clinical remissions between 5 and 19 years, of which 26 were continuously minimal residual disease (MRD) negative based on all samples collected after ASCT.

Study details: The data come from a partly prospective and partly retrospective study including 65 patients with disseminated MCL who received high-dose therapy with ASCT as first- (n = 54), second- (n = 10), or third-line (n = 1) treatment.

Disclosures: The MRD analysis was partly funded by BMBF (The Federal Ministry of Education and Research, Germany). M Dreyling declared serving on the scientific advisory boards of and receiving research support and speaker honoraria from various organizations. Other authors declared no conflicts of interest.

Source: Metzner B et al. Long-term outcome in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation. Eur J Haematol. 2023 (Apr 24). Doi: 10.1111/ejh.13985

Key clinical point: First-line autologous stem cell transplantation (ASCT) resulted in long-term clinical and molecular remissions in patients with disseminated mantle cell lymphoma (MCL).

Major finding: The 10-year overall survival, progression-free survival, and freedom from progression rates for the first-line vs second-line cohort were 64%, 52%, and 59% vs 50%, 20%, and 20%, respectively. Overall, 27 patients experienced sustained clinical remissions between 5 and 19 years, of which 26 were continuously minimal residual disease (MRD) negative based on all samples collected after ASCT.

Study details: The data come from a partly prospective and partly retrospective study including 65 patients with disseminated MCL who received high-dose therapy with ASCT as first- (n = 54), second- (n = 10), or third-line (n = 1) treatment.

Disclosures: The MRD analysis was partly funded by BMBF (The Federal Ministry of Education and Research, Germany). M Dreyling declared serving on the scientific advisory boards of and receiving research support and speaker honoraria from various organizations. Other authors declared no conflicts of interest.

Source: Metzner B et al. Long-term outcome in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation. Eur J Haematol. 2023 (Apr 24). Doi: 10.1111/ejh.13985

Key clinical point: First-line autologous stem cell transplantation (ASCT) resulted in long-term clinical and molecular remissions in patients with disseminated mantle cell lymphoma (MCL).

Major finding: The 10-year overall survival, progression-free survival, and freedom from progression rates for the first-line vs second-line cohort were 64%, 52%, and 59% vs 50%, 20%, and 20%, respectively. Overall, 27 patients experienced sustained clinical remissions between 5 and 19 years, of which 26 were continuously minimal residual disease (MRD) negative based on all samples collected after ASCT.

Study details: The data come from a partly prospective and partly retrospective study including 65 patients with disseminated MCL who received high-dose therapy with ASCT as first- (n = 54), second- (n = 10), or third-line (n = 1) treatment.

Disclosures: The MRD analysis was partly funded by BMBF (The Federal Ministry of Education and Research, Germany). M Dreyling declared serving on the scientific advisory boards of and receiving research support and speaker honoraria from various organizations. Other authors declared no conflicts of interest.

Source: Metzner B et al. Long-term outcome in patients with mantle cell lymphoma following high-dose therapy and autologous stem cell transplantation. Eur J Haematol. 2023 (Apr 24). Doi: 10.1111/ejh.13985

Key clinical point: Single nucleotide polymorphisms (SNP) of genes encoding specific cellular proteins may be associated with clinical outcomes and represent predictive biomarkers of poor response to lenalidomide maintenance after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL).

Major finding: Patients with ABCB1 or VEGF polymorphisms vs homozygous wild type (WT) in the lenalidomide arm had significantly higher 3-year progression-free survival (PFS) rates (85% vs 70%; P  =  .047 and 85% vs 60%; P  =  .0021, respectively). Lenalidomide vs observation did not improve 3-year PFS rates in patients carrying both ABCB1 and VEGF WT (P  =  .632).

Study details: This pharmacogenetic study included 278 adult patients with previously untreated MCL and adequate biological samples from the phase 3 MCL0208 study, 197 of whom were genotyped after ASCT and randomly assigned to the lenalidomide maintenance or observation arm.

Disclosures: This study was funded by Cancer Research UK and others. Some authors reported ties with various organizations.

Source: Ferrero S et al. Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: The FIL MCL0208 trial. Blood Adv. 2023 (Apr 14). Doi: 10.1182/bloodadvances.2022009504

Key clinical point: Single nucleotide polymorphisms (SNP) of genes encoding specific cellular proteins may be associated with clinical outcomes and represent predictive biomarkers of poor response to lenalidomide maintenance after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL).

Major finding: Patients with ABCB1 or VEGF polymorphisms vs homozygous wild type (WT) in the lenalidomide arm had significantly higher 3-year progression-free survival (PFS) rates (85% vs 70%; P  =  .047 and 85% vs 60%; P  =  .0021, respectively). Lenalidomide vs observation did not improve 3-year PFS rates in patients carrying both ABCB1 and VEGF WT (P  =  .632).

Study details: This pharmacogenetic study included 278 adult patients with previously untreated MCL and adequate biological samples from the phase 3 MCL0208 study, 197 of whom were genotyped after ASCT and randomly assigned to the lenalidomide maintenance or observation arm.

Disclosures: This study was funded by Cancer Research UK and others. Some authors reported ties with various organizations.

Source: Ferrero S et al. Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: The FIL MCL0208 trial. Blood Adv. 2023 (Apr 14). Doi: 10.1182/bloodadvances.2022009504

Key clinical point: Single nucleotide polymorphisms (SNP) of genes encoding specific cellular proteins may be associated with clinical outcomes and represent predictive biomarkers of poor response to lenalidomide maintenance after autologous stem cell transplantation (ASCT) in mantle cell lymphoma (MCL).

Major finding: Patients with ABCB1 or VEGF polymorphisms vs homozygous wild type (WT) in the lenalidomide arm had significantly higher 3-year progression-free survival (PFS) rates (85% vs 70%; P  =  .047 and 85% vs 60%; P  =  .0021, respectively). Lenalidomide vs observation did not improve 3-year PFS rates in patients carrying both ABCB1 and VEGF WT (P  =  .632).

Study details: This pharmacogenetic study included 278 adult patients with previously untreated MCL and adequate biological samples from the phase 3 MCL0208 study, 197 of whom were genotyped after ASCT and randomly assigned to the lenalidomide maintenance or observation arm.

Disclosures: This study was funded by Cancer Research UK and others. Some authors reported ties with various organizations.

Source: Ferrero S et al. Candidate germline biomarkers of lenalidomide efficacy in mantle cell lymphoma: The FIL MCL0208 trial. Blood Adv. 2023 (Apr 14). Doi: 10.1182/bloodadvances.2022009504

Key clinical point: The addition of venetoclax to ibrutinib treatment led to a high rate of undetectable measurable residual disease with 10^–4 sensitivity (U-MRD4) in the bone marrow (BM) in high-risk patients with chronic lymphocytic leukemia (CLL).

Major finding: Adding venetoclax to ibrutinib therapy led to a cumulative BM U-MRD4 rate of 73%. BM U-MRD4 was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively.

Study details: This phase 2 study included 45 patients with CLL and detectable disease (≥0.01% measurable residual disease in BM) treated with ibrutinib for ≥12 months who had ≥1 high-risk feature for disease progression and received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for ≤24 cycles.

Disclosures: This study was funded by AbbVie. Some authors declared serving as consultants or on speaker’s bureaus for or receiving advisory board or consulting honoraria or research support from AbbVie and others.

Source: Thompson PA et al. Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD. Leukemia. 2023 (May 3). Doi: 10.1038/s41375-023-01901-4

Key clinical point: The addition of venetoclax to ibrutinib treatment led to a high rate of undetectable measurable residual disease with 10^–4 sensitivity (U-MRD4) in the bone marrow (BM) in high-risk patients with chronic lymphocytic leukemia (CLL).

Major finding: Adding venetoclax to ibrutinib therapy led to a cumulative BM U-MRD4 rate of 73%. BM U-MRD4 was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively.

Study details: This phase 2 study included 45 patients with CLL and detectable disease (≥0.01% measurable residual disease in BM) treated with ibrutinib for ≥12 months who had ≥1 high-risk feature for disease progression and received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for ≤24 cycles.

Disclosures: This study was funded by AbbVie. Some authors declared serving as consultants or on speaker’s bureaus for or receiving advisory board or consulting honoraria or research support from AbbVie and others.

Source: Thompson PA et al. Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD. Leukemia. 2023 (May 3). Doi: 10.1038/s41375-023-01901-4

Key clinical point: The addition of venetoclax to ibrutinib treatment led to a high rate of undetectable measurable residual disease with 10^–4 sensitivity (U-MRD4) in the bone marrow (BM) in high-risk patients with chronic lymphocytic leukemia (CLL).

Major finding: Adding venetoclax to ibrutinib therapy led to a cumulative BM U-MRD4 rate of 73%. BM U-MRD4 was achieved by 71% of patients after venetoclax therapy completion and by 38% and 57% of patients after 6 and 12 cycles, respectively.

Study details: This phase 2 study included 45 patients with CLL and detectable disease (≥0.01% measurable residual disease in BM) treated with ibrutinib for ≥12 months who had ≥1 high-risk feature for disease progression and received combined treatment with ibrutinib (previously tolerated dose) and venetoclax (escalated to 400 mg once daily) for ≤24 cycles.

Disclosures: This study was funded by AbbVie. Some authors declared serving as consultants or on speaker’s bureaus for or receiving advisory board or consulting honoraria or research support from AbbVie and others.

Source: Thompson PA et al. Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD. Leukemia. 2023 (May 3). Doi: 10.1038/s41375-023-01901-4

Key clinical point: The addition of rituximab to chemotherapy increased the risk for prolonged hypogammaglobulinemia in children with high-risk mature B-cell non-Hodgkin lymphoma (B-NHL); however, severe infections after therapy completion were rare.

Major finding: At 1 year after therapy commencement, the chemotherapy+rituximab vs chemotherapy arm had a significantly higher proportion of children with low immunoglobulin G levels (55% vs 25%; odds ratio 3.64; P  =  .0003). The occurrence of grade ≥3 nonhematologic adverse events after 1 month of therapy completion was rare.

Study details: This secondary analysis of the Inter-B-NHL-Ritux 2010 trial included children (6 months-18 years) with high-risk mature B-NHL who were randomly (n = 289) or nonrandomly (n = 132) assigned to receive either chemotherapy alone or chemotherapy+rituximab.

Disclosures: The Inter-B-NHL-Ritux 2010 trial was supported by F Hoffmann-La Roche and others, and this study was funded by the National Cancer Institute of the US National Institutes of Health. Some authors reported ties with F Hoffmann-La Roche or other sources.

Source: Alexander S et al for the Children's Oncology Group and the European Intergroup for Childhood Non-Hodgkin's Lymphoma. Effect of rituximab on immune status in children with mature B-cell non-Hodgkin lymphoma: A prespecified secondary analysis of the Inter-B-NHL Ritux 2010 trial. Lancet Haematol. 2023 (Apr 21). Doi: 10.1016/S2352-3026(23)00062-5

Key clinical point: The addition of rituximab to chemotherapy increased the risk for prolonged hypogammaglobulinemia in children with high-risk mature B-cell non-Hodgkin lymphoma (B-NHL); however, severe infections after therapy completion were rare.

Major finding: At 1 year after therapy commencement, the chemotherapy+rituximab vs chemotherapy arm had a significantly higher proportion of children with low immunoglobulin G levels (55% vs 25%; odds ratio 3.64; P  =  .0003). The occurrence of grade ≥3 nonhematologic adverse events after 1 month of therapy completion was rare.

Study details: This secondary analysis of the Inter-B-NHL-Ritux 2010 trial included children (6 months-18 years) with high-risk mature B-NHL who were randomly (n = 289) or nonrandomly (n = 132) assigned to receive either chemotherapy alone or chemotherapy+rituximab.

Disclosures: The Inter-B-NHL-Ritux 2010 trial was supported by F Hoffmann-La Roche and others, and this study was funded by the National Cancer Institute of the US National Institutes of Health. Some authors reported ties with F Hoffmann-La Roche or other sources.

Source: Alexander S et al for the Children's Oncology Group and the European Intergroup for Childhood Non-Hodgkin's Lymphoma. Effect of rituximab on immune status in children with mature B-cell non-Hodgkin lymphoma: A prespecified secondary analysis of the Inter-B-NHL Ritux 2010 trial. Lancet Haematol. 2023 (Apr 21). Doi: 10.1016/S2352-3026(23)00062-5

Key clinical point: The addition of rituximab to chemotherapy increased the risk for prolonged hypogammaglobulinemia in children with high-risk mature B-cell non-Hodgkin lymphoma (B-NHL); however, severe infections after therapy completion were rare.

Major finding: At 1 year after therapy commencement, the chemotherapy+rituximab vs chemotherapy arm had a significantly higher proportion of children with low immunoglobulin G levels (55% vs 25%; odds ratio 3.64; P  =  .0003). The occurrence of grade ≥3 nonhematologic adverse events after 1 month of therapy completion was rare.

Study details: This secondary analysis of the Inter-B-NHL-Ritux 2010 trial included children (6 months-18 years) with high-risk mature B-NHL who were randomly (n = 289) or nonrandomly (n = 132) assigned to receive either chemotherapy alone or chemotherapy+rituximab.

Disclosures: The Inter-B-NHL-Ritux 2010 trial was supported by F Hoffmann-La Roche and others, and this study was funded by the National Cancer Institute of the US National Institutes of Health. Some authors reported ties with F Hoffmann-La Roche or other sources.

Source: Alexander S et al for the Children's Oncology Group and the European Intergroup for Childhood Non-Hodgkin's Lymphoma. Effect of rituximab on immune status in children with mature B-cell non-Hodgkin lymphoma: A prespecified secondary analysis of the Inter-B-NHL Ritux 2010 trial. Lancet Haematol. 2023 (Apr 21). Doi: 10.1016/S2352-3026(23)00062-5

Key clinical point: Compared with the standard intravenous (IV) rituximab induction therapy, a short subcutaneous rituximab maintenance therapy after subcutaneous rituximab induction therapy improves complete response (CR) and progression-free survival (PFS) in patients with CD20⁺ low-tumor burden follicular lymphoma (FL).

Major finding: Patients receiving rituximab induction (first IV and then subcutaneous) followed by a short subcutaneous rituximab maintenance therapy (four infusions; experimental arm) vs four weekly IV rituximab infusions (control arm) had significantly higher 4-year PFS (58.1% vs 41.2%; hazard ratio 0.585; P  =  .008) and CR (59.0% vs 36.3%; P  =  .001) rates.

Study details: Findings are from a phase 3 study, FLIRT, that included 202 patients with CD20⁺ low-tumor burden FL who were randomly assigned to the control or experimental arm.

Disclosures: This study was supported by the Lymphoma Academic Research Organization (LYSARC), France. Some authors declared serving as consultants or advisors for or receiving honoraria, research funding, or travel and accommodation expenses from various sources.

Source: Cartron G et al. Randomized phase III trial evaluating subcutaneous rituximab for the first-line treatment of low–tumor burden follicular lymphoma: Results of a LYSA study. J Clin Oncol. 2023 (Apr 18). Doi: 10.1200/JCO.22.02327

Key clinical point: Compared with the standard intravenous (IV) rituximab induction therapy, a short subcutaneous rituximab maintenance therapy after subcutaneous rituximab induction therapy improves complete response (CR) and progression-free survival (PFS) in patients with CD20⁺ low-tumor burden follicular lymphoma (FL).

Major finding: Patients receiving rituximab induction (first IV and then subcutaneous) followed by a short subcutaneous rituximab maintenance therapy (four infusions; experimental arm) vs four weekly IV rituximab infusions (control arm) had significantly higher 4-year PFS (58.1% vs 41.2%; hazard ratio 0.585; P  =  .008) and CR (59.0% vs 36.3%; P  =  .001) rates.

Study details: Findings are from a phase 3 study, FLIRT, that included 202 patients with CD20⁺ low-tumor burden FL who were randomly assigned to the control or experimental arm.

Disclosures: This study was supported by the Lymphoma Academic Research Organization (LYSARC), France. Some authors declared serving as consultants or advisors for or receiving honoraria, research funding, or travel and accommodation expenses from various sources.

Source: Cartron G et al. Randomized phase III trial evaluating subcutaneous rituximab for the first-line treatment of low–tumor burden follicular lymphoma: Results of a LYSA study. J Clin Oncol. 2023 (Apr 18). Doi: 10.1200/JCO.22.02327

Key clinical point: Compared with the standard intravenous (IV) rituximab induction therapy, a short subcutaneous rituximab maintenance therapy after subcutaneous rituximab induction therapy improves complete response (CR) and progression-free survival (PFS) in patients with CD20⁺ low-tumor burden follicular lymphoma (FL).

Major finding: Patients receiving rituximab induction (first IV and then subcutaneous) followed by a short subcutaneous rituximab maintenance therapy (four infusions; experimental arm) vs four weekly IV rituximab infusions (control arm) had significantly higher 4-year PFS (58.1% vs 41.2%; hazard ratio 0.585; P  =  .008) and CR (59.0% vs 36.3%; P  =  .001) rates.

Study details: Findings are from a phase 3 study, FLIRT, that included 202 patients with CD20⁺ low-tumor burden FL who were randomly assigned to the control or experimental arm.

Disclosures: This study was supported by the Lymphoma Academic Research Organization (LYSARC), France. Some authors declared serving as consultants or advisors for or receiving honoraria, research funding, or travel and accommodation expenses from various sources.

Source: Cartron G et al. Randomized phase III trial evaluating subcutaneous rituximab for the first-line treatment of low–tumor burden follicular lymphoma: Results of a LYSA study. J Clin Oncol. 2023 (Apr 18). Doi: 10.1200/JCO.22.02327

Key clinical point: Compared with fludarabine, cyclophosphamide, and rituximab, ibrutinib and rituximab provided a significant progression-free survival (PFS) benefit in treatment-naive patients with chronic lymphocytic leukemia (CLL).

Major finding: After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib and rituximab and was 67 months (95% CI 63-not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (hazard ratio 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib and rituximab group.

Study details: This interim analysis of the multicenter phase 3 FLAIR trial included 771 treatment-naive adult patients with CLL or small lymphocytic lymphoma who were randomly assigned to receive ibrutinib and rituximab (n = 386) or fludarabine, cyclophosphamide, and rituximab (n = 385).

Disclosures: This study was funded by Cancer Research UK, Janssen, and others. Some authors declared participating on data safety monitoring or advisory boards and receiving grants, personal consulting or speaker fees, lecture honoraria, or travel support from the study funders and others.

Source: Hillmen P et al. Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): Interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(5):535-552 (May). Doi: 10.1016/S1470-2045(23)00144-4

Key clinical point: Compared with fludarabine, cyclophosphamide, and rituximab, ibrutinib and rituximab provided a significant progression-free survival (PFS) benefit in treatment-naive patients with chronic lymphocytic leukemia (CLL).

Major finding: After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib and rituximab and was 67 months (95% CI 63-not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (hazard ratio 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib and rituximab group.

Study details: This interim analysis of the multicenter phase 3 FLAIR trial included 771 treatment-naive adult patients with CLL or small lymphocytic lymphoma who were randomly assigned to receive ibrutinib and rituximab (n = 386) or fludarabine, cyclophosphamide, and rituximab (n = 385).

Disclosures: This study was funded by Cancer Research UK, Janssen, and others. Some authors declared participating on data safety monitoring or advisory boards and receiving grants, personal consulting or speaker fees, lecture honoraria, or travel support from the study funders and others.

Source: Hillmen P et al. Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): Interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(5):535-552 (May). Doi: 10.1016/S1470-2045(23)00144-4

Key clinical point: Compared with fludarabine, cyclophosphamide, and rituximab, ibrutinib and rituximab provided a significant progression-free survival (PFS) benefit in treatment-naive patients with chronic lymphocytic leukemia (CLL).

Major finding: After a median follow-up of 53 months, the median PFS was not reached in patients receiving ibrutinib and rituximab and was 67 months (95% CI 63-not reached) in those receiving fludarabine, cyclophosphamide, and rituximab (hazard ratio 0.44; P < .0001). A substantial number of sudden cardiac or unexplained deaths occurred, which were more frequent in the ibrutinib and rituximab group.

Study details: This interim analysis of the multicenter phase 3 FLAIR trial included 771 treatment-naive adult patients with CLL or small lymphocytic lymphoma who were randomly assigned to receive ibrutinib and rituximab (n = 386) or fludarabine, cyclophosphamide, and rituximab (n = 385).

Disclosures: This study was funded by Cancer Research UK, Janssen, and others. Some authors declared participating on data safety monitoring or advisory boards and receiving grants, personal consulting or speaker fees, lecture honoraria, or travel support from the study funders and others.

Source: Hillmen P et al. Ibrutinib and rituximab versus fludarabine, cyclophosphamide, and rituximab for patients with previously untreated chronic lymphocytic leukaemia (FLAIR): Interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023;24(5):535-552 (May). Doi: 10.1016/S1470-2045(23)00144-4

Key clinical point: Compared with the current standard chemoimmunotherapy, venetoclax-obinutuzumab with or without ibrutinib as first line treatment improved outcomes in fit patients with advanced chronic lymphocytic leukemia (CLL).

Major finding: The venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib groups vs the chemoimmunotherapy group had significantly higher undetectable minimal residual disease rates at 15 months (86.5% and 92.2% vs 52.0%, respectively; both P < .001) and 3-year progression-free survival (hazard ratio for disease progression or death 0.42 and 0.32, respectively; both P < .001) and numerically lower fatal adverse event rate (3.9% and 3.9% vs 4.6%, respectively).

Study details: This phase 3 trial, GAIA-CLL13, included 926 fit adult patients with previously untreated, advanced CLL and no del(17p) or TP53 mutations who were randomly assigned to receive standard chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab), venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib.

Disclosures: This study was supported by AbbVie, Janssen, and Roche. Some authors declared serving as consultants, advisory board members, or speakers and receiving research grants, speaker honoraria, or travel support from the study funders and others.

Source: Eichhorst B et al for the GCLLSG, the HOVON and Nordic CLL Study Groups, the SAKK, the Israeli CLL Association, and Cancer Trials Ireland. First-line venetoclax combinations in chronic lymphocytic leukemia. N Engl J Med. 2023;388(19):1739-1754 (May 11). Doi: 10.1056/NEJMoa2213093

Key clinical point: Compared with the current standard chemoimmunotherapy, venetoclax-obinutuzumab with or without ibrutinib as first line treatment improved outcomes in fit patients with advanced chronic lymphocytic leukemia (CLL).

Major finding: The venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib groups vs the chemoimmunotherapy group had significantly higher undetectable minimal residual disease rates at 15 months (86.5% and 92.2% vs 52.0%, respectively; both P < .001) and 3-year progression-free survival (hazard ratio for disease progression or death 0.42 and 0.32, respectively; both P < .001) and numerically lower fatal adverse event rate (3.9% and 3.9% vs 4.6%, respectively).

Study details: This phase 3 trial, GAIA-CLL13, included 926 fit adult patients with previously untreated, advanced CLL and no del(17p) or TP53 mutations who were randomly assigned to receive standard chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab), venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib.

Disclosures: This study was supported by AbbVie, Janssen, and Roche. Some authors declared serving as consultants, advisory board members, or speakers and receiving research grants, speaker honoraria, or travel support from the study funders and others.

Source: Eichhorst B et al for the GCLLSG, the HOVON and Nordic CLL Study Groups, the SAKK, the Israeli CLL Association, and Cancer Trials Ireland. First-line venetoclax combinations in chronic lymphocytic leukemia. N Engl J Med. 2023;388(19):1739-1754 (May 11). Doi: 10.1056/NEJMoa2213093

Key clinical point: Compared with the current standard chemoimmunotherapy, venetoclax-obinutuzumab with or without ibrutinib as first line treatment improved outcomes in fit patients with advanced chronic lymphocytic leukemia (CLL).

Major finding: The venetoclax-obinutuzumab and venetoclax-obinutuzumab-ibrutinib groups vs the chemoimmunotherapy group had significantly higher undetectable minimal residual disease rates at 15 months (86.5% and 92.2% vs 52.0%, respectively; both P < .001) and 3-year progression-free survival (hazard ratio for disease progression or death 0.42 and 0.32, respectively; both P < .001) and numerically lower fatal adverse event rate (3.9% and 3.9% vs 4.6%, respectively).

Study details: This phase 3 trial, GAIA-CLL13, included 926 fit adult patients with previously untreated, advanced CLL and no del(17p) or TP53 mutations who were randomly assigned to receive standard chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab), venetoclax-rituximab, venetoclax-obinutuzumab, or venetoclax-obinutuzumab-ibrutinib.

Disclosures: This study was supported by AbbVie, Janssen, and Roche. Some authors declared serving as consultants, advisory board members, or speakers and receiving research grants, speaker honoraria, or travel support from the study funders and others.

Source: Eichhorst B et al for the GCLLSG, the HOVON and Nordic CLL Study Groups, the SAKK, the Israeli CLL Association, and Cancer Trials Ireland. First-line venetoclax combinations in chronic lymphocytic leukemia. N Engl J Med. 2023;388(19):1739-1754 (May 11). Doi: 10.1056/NEJMoa2213093

Key clinical point: The risk for all-cause mortality is higher among elderly patients with vs without rheumatoid arthritis (RA) who undergo percutaneous coronary intervention (PCI), with the risk being the highest among those with elderly-onset RA (disease presentation after 65 years of age).

Major finding: During the 10-year follow-up, all-cause mortality-associated survival rates were significantly lower in patients with vs without RA (53.7% vs 58.3%; log-rank P < .001) and in patients with elderly-onset vs young-onset RA (48.1% vs 73.7%; log-rank P < .001). Trends were similar for cardiovascular disease-associated survival rates (all log-rank P < .001).

Study details: This was a population-based retrospective cohort study including 74,623 patients age ≥ 65 years with (n = 14,074) or without (n = 60,549) RA who were diagnosed with acute coronary syndrome and underwent PCI.

Disclosures: This study was funded by Soonchunhyang University, South Korea, and the Asan Foundation, South Korea. The authors declared no conflicts of interest.

Source: Kim BY et al. Outcomes of percutaneous coronary intervention in elderly patients with rheumatoid arthritis: A nationwide population-based cohort study. Healthcare (Basel). 2023;11(10):1381 (May 10). Doi: 10.3390/healthcare11101381

Key clinical point: The risk for all-cause mortality is higher among elderly patients with vs without rheumatoid arthritis (RA) who undergo percutaneous coronary intervention (PCI), with the risk being the highest among those with elderly-onset RA (disease presentation after 65 years of age).

Major finding: During the 10-year follow-up, all-cause mortality-associated survival rates were significantly lower in patients with vs without RA (53.7% vs 58.3%; log-rank P < .001) and in patients with elderly-onset vs young-onset RA (48.1% vs 73.7%; log-rank P < .001). Trends were similar for cardiovascular disease-associated survival rates (all log-rank P < .001).

Study details: This was a population-based retrospective cohort study including 74,623 patients age ≥ 65 years with (n = 14,074) or without (n = 60,549) RA who were diagnosed with acute coronary syndrome and underwent PCI.

Disclosures: This study was funded by Soonchunhyang University, South Korea, and the Asan Foundation, South Korea. The authors declared no conflicts of interest.

Source: Kim BY et al. Outcomes of percutaneous coronary intervention in elderly patients with rheumatoid arthritis: A nationwide population-based cohort study. Healthcare (Basel). 2023;11(10):1381 (May 10). Doi: 10.3390/healthcare11101381

Key clinical point: The risk for all-cause mortality is higher among elderly patients with vs without rheumatoid arthritis (RA) who undergo percutaneous coronary intervention (PCI), with the risk being the highest among those with elderly-onset RA (disease presentation after 65 years of age).

Major finding: During the 10-year follow-up, all-cause mortality-associated survival rates were significantly lower in patients with vs without RA (53.7% vs 58.3%; log-rank P < .001) and in patients with elderly-onset vs young-onset RA (48.1% vs 73.7%; log-rank P < .001). Trends were similar for cardiovascular disease-associated survival rates (all log-rank P < .001).

Study details: This was a population-based retrospective cohort study including 74,623 patients age ≥ 65 years with (n = 14,074) or without (n = 60,549) RA who were diagnosed with acute coronary syndrome and underwent PCI.

Disclosures: This study was funded by Soonchunhyang University, South Korea, and the Asan Foundation, South Korea. The authors declared no conflicts of interest.

Source: Kim BY et al. Outcomes of percutaneous coronary intervention in elderly patients with rheumatoid arthritis: A nationwide population-based cohort study. Healthcare (Basel). 2023;11(10):1381 (May 10). Doi: 10.3390/healthcare11101381

Key clinical point: Patients with rheumatoid arthritis (RA) were at an increased risk for Parkinson disease (PD), and patients with seropositive RA had an augmented risk for PD.

Major finding: The risk for PD was 1.74-fold higher in patients with RA vs control individuals without RA (adjusted hazard ratio [aHR] 1.74; 95% CI 1.52-1.99), 1.95-fold higher in patients with seropositive RA vs control individuals without RA (aHR 1.95; 95% CI 1.68-2.26), and 1.61-fold higher in patients with seropositive vs seronegative RA (aHR 1.61; 95% CI 1.20-2.16).

Study details: Findings are from a retrospective cohort study including 54,680 patients with RA (seropositive RA n = 39,010, and seronegative RA n = 15,670) and 273,400 age- and sex-matched control individuals without RA.

Disclosures: This study did not declare the source of funding or any conflicts of interest.

Source: Kang J et al. Rheumatoid arthritis and risk of Parkinson disease in Korea. JAMA Neurol. 2023 (May 1). Doi: 10.1001/jamaneurol.2023.0932

Key clinical point: Patients with rheumatoid arthritis (RA) were at an increased risk for Parkinson disease (PD), and patients with seropositive RA had an augmented risk for PD.

Major finding: The risk for PD was 1.74-fold higher in patients with RA vs control individuals without RA (adjusted hazard ratio [aHR] 1.74; 95% CI 1.52-1.99), 1.95-fold higher in patients with seropositive RA vs control individuals without RA (aHR 1.95; 95% CI 1.68-2.26), and 1.61-fold higher in patients with seropositive vs seronegative RA (aHR 1.61; 95% CI 1.20-2.16).

Study details: Findings are from a retrospective cohort study including 54,680 patients with RA (seropositive RA n = 39,010, and seronegative RA n = 15,670) and 273,400 age- and sex-matched control individuals without RA.

Disclosures: This study did not declare the source of funding or any conflicts of interest.

Source: Kang J et al. Rheumatoid arthritis and risk of Parkinson disease in Korea. JAMA Neurol. 2023 (May 1). Doi: 10.1001/jamaneurol.2023.0932

Key clinical point: Patients with rheumatoid arthritis (RA) were at an increased risk for Parkinson disease (PD), and patients with seropositive RA had an augmented risk for PD.

Major finding: The risk for PD was 1.74-fold higher in patients with RA vs control individuals without RA (adjusted hazard ratio [aHR] 1.74; 95% CI 1.52-1.99), 1.95-fold higher in patients with seropositive RA vs control individuals without RA (aHR 1.95; 95% CI 1.68-2.26), and 1.61-fold higher in patients with seropositive vs seronegative RA (aHR 1.61; 95% CI 1.20-2.16).

Study details: Findings are from a retrospective cohort study including 54,680 patients with RA (seropositive RA n = 39,010, and seronegative RA n = 15,670) and 273,400 age- and sex-matched control individuals without RA.

Disclosures: This study did not declare the source of funding or any conflicts of interest.

Source: Kang J et al. Rheumatoid arthritis and risk of Parkinson disease in Korea. JAMA Neurol. 2023 (May 1). Doi: 10.1001/jamaneurol.2023.0932