Key clinical point: Only the copresence of TP53 deletion (del17p) and mutations and not a single aberration has a negative prognostic impact in patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib treatment.

Major finding: Only patients with concomitant TP53 mutations and del17p had significantly shorter overall survival (OS; P = .0073) and progression-free survival (PFS; P = .0037) than those with no TP53 aberration; no difference in OS or PFS was observed in patients with single aberration. TP53 mutation and del17p copresence was an independent predictor for short OS and PFS (adjusted hazard ratio 2.27; P = .0077).

Study details: This multicenter retrospective study included 229 patients with CLL treated with ibrutinib who were assayed for TP53 mutation and del17p in the same blood sample that was collected within 6 months before initiating ibrutinib.

Disclosures: This study was supported in part by the Italian Ministry of Health “Progetto Ricerca Finalizzata” and others. The authors declared no conflicts of interest.

Source: Bomben R et al. Clinical impact of TP53 disruption in chronic lymphocytic leukemia patients treated with ibrutinib: A campus CLL study. Leukemia. 2023 (Feb 18). Doi: 10.1038/s41375-023-01845-9

Key clinical point: Only the copresence of TP53 deletion (del17p) and mutations and not a single aberration has a negative prognostic impact in patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib treatment.

Major finding: Only patients with concomitant TP53 mutations and del17p had significantly shorter overall survival (OS; P = .0073) and progression-free survival (PFS; P = .0037) than those with no TP53 aberration; no difference in OS or PFS was observed in patients with single aberration. TP53 mutation and del17p copresence was an independent predictor for short OS and PFS (adjusted hazard ratio 2.27; P = .0077).

Study details: This multicenter retrospective study included 229 patients with CLL treated with ibrutinib who were assayed for TP53 mutation and del17p in the same blood sample that was collected within 6 months before initiating ibrutinib.

Disclosures: This study was supported in part by the Italian Ministry of Health “Progetto Ricerca Finalizzata” and others. The authors declared no conflicts of interest.

Source: Bomben R et al. Clinical impact of TP53 disruption in chronic lymphocytic leukemia patients treated with ibrutinib: A campus CLL study. Leukemia. 2023 (Feb 18). Doi: 10.1038/s41375-023-01845-9

Key clinical point: Only the copresence of TP53 deletion (del17p) and mutations and not a single aberration has a negative prognostic impact in patients with chronic lymphocytic leukemia (CLL) receiving ibrutinib treatment.

Major finding: Only patients with concomitant TP53 mutations and del17p had significantly shorter overall survival (OS; P = .0073) and progression-free survival (PFS; P = .0037) than those with no TP53 aberration; no difference in OS or PFS was observed in patients with single aberration. TP53 mutation and del17p copresence was an independent predictor for short OS and PFS (adjusted hazard ratio 2.27; P = .0077).

Study details: This multicenter retrospective study included 229 patients with CLL treated with ibrutinib who were assayed for TP53 mutation and del17p in the same blood sample that was collected within 6 months before initiating ibrutinib.

Disclosures: This study was supported in part by the Italian Ministry of Health “Progetto Ricerca Finalizzata” and others. The authors declared no conflicts of interest.

Source: Bomben R et al. Clinical impact of TP53 disruption in chronic lymphocytic leukemia patients treated with ibrutinib: A campus CLL study. Leukemia. 2023 (Feb 18). Doi: 10.1038/s41375-023-01845-9

Key clinical point: Grade 3B follicular lymphoma (G3BFL) has similar survival outcomes to grade 3A FL (G3AFL) but a superior prognosis than diffuse large B-cell lymphoma (DLBCL) in immunotherapy-treated patients.

Major finding: At a median follow-up of 5 years, the G3BFL vs DLBCL group had a significantly longer progression-free survival (PFS; hazard ratio [HR] 1.73; P = .001) and overall survival (OS; HR 2.19; P ≤ .001), whereas PFS (HR 1.04; P = .81) and OS (HR 1.04; P = .84) were similar between the G3BFL and G3AFL groups.

Study details: This multicenter study analyzed the data of 157 patients with G3BFL, 302 patients with G3AFL, and 548 patients with DLBCL treated with rituximab/obinutuzumab, cyclophosphamide, doxorubicin, vincristine, and prednisolone-like chemotherapy with or without radiotherapy or bendamustine-rituximab.

Disclosures: The study did not receive any funding. Some authors reported ties with various organizations.

Source: Barraclough A et al. Outcomes in grade 3B follicular lymphoma: an international study led by the Australasian Lymphoma Alliance. Haematologica. 2023 (Feb 23). Doi: 10.3324/haematol.2022.281375

Key clinical point: Grade 3B follicular lymphoma (G3BFL) has similar survival outcomes to grade 3A FL (G3AFL) but a superior prognosis than diffuse large B-cell lymphoma (DLBCL) in immunotherapy-treated patients.

Major finding: At a median follow-up of 5 years, the G3BFL vs DLBCL group had a significantly longer progression-free survival (PFS; hazard ratio [HR] 1.73; P = .001) and overall survival (OS; HR 2.19; P ≤ .001), whereas PFS (HR 1.04; P = .81) and OS (HR 1.04; P = .84) were similar between the G3BFL and G3AFL groups.

Study details: This multicenter study analyzed the data of 157 patients with G3BFL, 302 patients with G3AFL, and 548 patients with DLBCL treated with rituximab/obinutuzumab, cyclophosphamide, doxorubicin, vincristine, and prednisolone-like chemotherapy with or without radiotherapy or bendamustine-rituximab.

Disclosures: The study did not receive any funding. Some authors reported ties with various organizations.

Source: Barraclough A et al. Outcomes in grade 3B follicular lymphoma: an international study led by the Australasian Lymphoma Alliance. Haematologica. 2023 (Feb 23). Doi: 10.3324/haematol.2022.281375

Key clinical point: Grade 3B follicular lymphoma (G3BFL) has similar survival outcomes to grade 3A FL (G3AFL) but a superior prognosis than diffuse large B-cell lymphoma (DLBCL) in immunotherapy-treated patients.

Major finding: At a median follow-up of 5 years, the G3BFL vs DLBCL group had a significantly longer progression-free survival (PFS; hazard ratio [HR] 1.73; P = .001) and overall survival (OS; HR 2.19; P ≤ .001), whereas PFS (HR 1.04; P = .81) and OS (HR 1.04; P = .84) were similar between the G3BFL and G3AFL groups.

Study details: This multicenter study analyzed the data of 157 patients with G3BFL, 302 patients with G3AFL, and 548 patients with DLBCL treated with rituximab/obinutuzumab, cyclophosphamide, doxorubicin, vincristine, and prednisolone-like chemotherapy with or without radiotherapy or bendamustine-rituximab.

Disclosures: The study did not receive any funding. Some authors reported ties with various organizations.

Source: Barraclough A et al. Outcomes in grade 3B follicular lymphoma: an international study led by the Australasian Lymphoma Alliance. Haematologica. 2023 (Feb 23). Doi: 10.3324/haematol.2022.281375

Key clinical point: Addition of ibrutinib to rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) provided no survival benefit in children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL).

Major finding: Patients receiving ibrutinib plus RICE/RVICI vs RICE/RVICI alone had similar median event-free survival (6.1 vs 7.0 months; hazard ratio [HR] 0.9; P = .387) and median overall survival (14.1 vs 11.1 months; HR 0.9; P = .789). All patients experienced grade ≥3 treatment-emergent adverse events.

Study details: Findings represent the final results of SPARKLE trial Part 2 that included 51 patients aged 1-30 years with relapsed or refractory mature B-NHL who were randomly assigned to receive ibrutinib plus RICE/RVICI (n = 35) or RICE/RVICI alone (n = 16).

Disclosures: This study was funded by Janssen Research and Development. Some authors reported ties with various organizations, including Janssen. Six authors declared being employees of Janssen or holding stocks in Johnson & Johnson.

Source: Burke GAA et al. Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial. Blood Adv. 2023;7(4):602-610 (Feb 20). Doi: 10.1182/bloodadvances.2022008802

Key clinical point: Addition of ibrutinib to rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) provided no survival benefit in children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL).

Major finding: Patients receiving ibrutinib plus RICE/RVICI vs RICE/RVICI alone had similar median event-free survival (6.1 vs 7.0 months; hazard ratio [HR] 0.9; P = .387) and median overall survival (14.1 vs 11.1 months; HR 0.9; P = .789). All patients experienced grade ≥3 treatment-emergent adverse events.

Study details: Findings represent the final results of SPARKLE trial Part 2 that included 51 patients aged 1-30 years with relapsed or refractory mature B-NHL who were randomly assigned to receive ibrutinib plus RICE/RVICI (n = 35) or RICE/RVICI alone (n = 16).

Disclosures: This study was funded by Janssen Research and Development. Some authors reported ties with various organizations, including Janssen. Six authors declared being employees of Janssen or holding stocks in Johnson & Johnson.

Source: Burke GAA et al. Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial. Blood Adv. 2023;7(4):602-610 (Feb 20). Doi: 10.1182/bloodadvances.2022008802

Key clinical point: Addition of ibrutinib to rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) provided no survival benefit in children and young adults with relapsed or refractory mature B-cell non-Hodgkin lymphoma (B-NHL).

Major finding: Patients receiving ibrutinib plus RICE/RVICI vs RICE/RVICI alone had similar median event-free survival (6.1 vs 7.0 months; hazard ratio [HR] 0.9; P = .387) and median overall survival (14.1 vs 11.1 months; HR 0.9; P = .789). All patients experienced grade ≥3 treatment-emergent adverse events.

Study details: Findings represent the final results of SPARKLE trial Part 2 that included 51 patients aged 1-30 years with relapsed or refractory mature B-NHL who were randomly assigned to receive ibrutinib plus RICE/RVICI (n = 35) or RICE/RVICI alone (n = 16).

Disclosures: This study was funded by Janssen Research and Development. Some authors reported ties with various organizations, including Janssen. Six authors declared being employees of Janssen or holding stocks in Johnson & Johnson.

Source: Burke GAA et al. Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial. Blood Adv. 2023;7(4):602-610 (Feb 20). Doi: 10.1182/bloodadvances.2022008802

Key clinical point: Long-term zanubrutinib monotherapy continued to yield high response and survival rates in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without compromising safety.

Major finding: At a median follow-up of 34 months, the overall response rate was 87.9% (95% CI 79.4%-93.8%). The median progression-free survival (PFS) or overall survival (OS) was not reached; the estimated PFS event-free and OS rates at 30 months were 75.7% (95% CI 65.2%-83.4%) and 88.6% (95% CI 79.8%-93.7%), respectively. No new safety signals were identified.

Study details: This long-term follow-up analysis of a phase 2 study included 91 patients with CLL/SLL who relapsed after or were refractory to ≥1 prior line of therapy and received 160 mg oral zanubrutinib twice daily.

Disclosures: The phase 2 study was sponsored by BeiGene (Beijing) Co., Ltd., China, and BeiGene USA, Inc., USA. Some authors declared being employees of and holding stocks in BeiGene.

Source: Xu W et al. Zanubrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Final results and correlative analysis of lymphocytosis. Leuk Lymphoma. 2023;1-5 (Feb 17). Doi: 10.1080/10428194.2022.2164692

Key clinical point: Long-term zanubrutinib monotherapy continued to yield high response and survival rates in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without compromising safety.

Major finding: At a median follow-up of 34 months, the overall response rate was 87.9% (95% CI 79.4%-93.8%). The median progression-free survival (PFS) or overall survival (OS) was not reached; the estimated PFS event-free and OS rates at 30 months were 75.7% (95% CI 65.2%-83.4%) and 88.6% (95% CI 79.8%-93.7%), respectively. No new safety signals were identified.

Study details: This long-term follow-up analysis of a phase 2 study included 91 patients with CLL/SLL who relapsed after or were refractory to ≥1 prior line of therapy and received 160 mg oral zanubrutinib twice daily.

Disclosures: The phase 2 study was sponsored by BeiGene (Beijing) Co., Ltd., China, and BeiGene USA, Inc., USA. Some authors declared being employees of and holding stocks in BeiGene.

Source: Xu W et al. Zanubrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Final results and correlative analysis of lymphocytosis. Leuk Lymphoma. 2023;1-5 (Feb 17). Doi: 10.1080/10428194.2022.2164692

Key clinical point: Long-term zanubrutinib monotherapy continued to yield high response and survival rates in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without compromising safety.

Major finding: At a median follow-up of 34 months, the overall response rate was 87.9% (95% CI 79.4%-93.8%). The median progression-free survival (PFS) or overall survival (OS) was not reached; the estimated PFS event-free and OS rates at 30 months were 75.7% (95% CI 65.2%-83.4%) and 88.6% (95% CI 79.8%-93.7%), respectively. No new safety signals were identified.

Study details: This long-term follow-up analysis of a phase 2 study included 91 patients with CLL/SLL who relapsed after or were refractory to ≥1 prior line of therapy and received 160 mg oral zanubrutinib twice daily.

Disclosures: The phase 2 study was sponsored by BeiGene (Beijing) Co., Ltd., China, and BeiGene USA, Inc., USA. Some authors declared being employees of and holding stocks in BeiGene.

Source: Xu W et al. Zanubrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: Final results and correlative analysis of lymphocytosis. Leuk Lymphoma. 2023;1-5 (Feb 17). Doi: 10.1080/10428194.2022.2164692

Key clinical point: Patients hospitalized with immune thrombocytopenia (ITP) and concomitant chronic lymphocytic leukemia (CLL) have a greater risk for death, require more blood products, and have poorer hospitalization outcomes compared with those with ITP without CLL.

Major finding: The risks for all-cause mortality (adjusted odds ratio [aOR] 1.28), gastrointestinal bleeding (aOR 1.19), packed red blood cell transfusion (aOR 1.79), splenectomy (aOR 1.30), and platelet transfusion (aOR, 1.49) were higher in patients with ITP and CLL vs those with ITP without CLL (all P < .01).

Study details: The data come from a retrospective study including patients hospitalized for ITP who did (n = 15,672) and did not (n = 646,499) have concurrent CLL.

Disclosures: This study did not report the source of funding. Some authors declared receiving research grants or consulting fees from various sources.

Source: Ammad Ud Din M et al. Risks and outcomes of hospitalizations in patients with chronic lymphocytic leukemia admitted with immune thrombocytopenia: An analysis of the National Inpatient Sample Database. Ann Hematol. 2023;102(4):889-895 (Feb 13). Doi: 10.1007/s00277-023-05133-5

Key clinical point: Patients hospitalized with immune thrombocytopenia (ITP) and concomitant chronic lymphocytic leukemia (CLL) have a greater risk for death, require more blood products, and have poorer hospitalization outcomes compared with those with ITP without CLL.

Major finding: The risks for all-cause mortality (adjusted odds ratio [aOR] 1.28), gastrointestinal bleeding (aOR 1.19), packed red blood cell transfusion (aOR 1.79), splenectomy (aOR 1.30), and platelet transfusion (aOR, 1.49) were higher in patients with ITP and CLL vs those with ITP without CLL (all P < .01).

Study details: The data come from a retrospective study including patients hospitalized for ITP who did (n = 15,672) and did not (n = 646,499) have concurrent CLL.

Disclosures: This study did not report the source of funding. Some authors declared receiving research grants or consulting fees from various sources.

Source: Ammad Ud Din M et al. Risks and outcomes of hospitalizations in patients with chronic lymphocytic leukemia admitted with immune thrombocytopenia: An analysis of the National Inpatient Sample Database. Ann Hematol. 2023;102(4):889-895 (Feb 13). Doi: 10.1007/s00277-023-05133-5

Key clinical point: Patients hospitalized with immune thrombocytopenia (ITP) and concomitant chronic lymphocytic leukemia (CLL) have a greater risk for death, require more blood products, and have poorer hospitalization outcomes compared with those with ITP without CLL.

Major finding: The risks for all-cause mortality (adjusted odds ratio [aOR] 1.28), gastrointestinal bleeding (aOR 1.19), packed red blood cell transfusion (aOR 1.79), splenectomy (aOR 1.30), and platelet transfusion (aOR, 1.49) were higher in patients with ITP and CLL vs those with ITP without CLL (all P < .01).

Study details: The data come from a retrospective study including patients hospitalized for ITP who did (n = 15,672) and did not (n = 646,499) have concurrent CLL.

Disclosures: This study did not report the source of funding. Some authors declared receiving research grants or consulting fees from various sources.

Source: Ammad Ud Din M et al. Risks and outcomes of hospitalizations in patients with chronic lymphocytic leukemia admitted with immune thrombocytopenia: An analysis of the National Inpatient Sample Database. Ann Hematol. 2023;102(4):889-895 (Feb 13). Doi: 10.1007/s00277-023-05133-5

Key clinical point: Axicabtagene ciloleucel (axi-cel) led to a durable response and long-term survival in patients with refractory large B-cell lymphoma (LBCL), with no new safety signals.

Major finding: At a median follow-up of 63.1 months from infusion, the objective and complete response rates were 83% (95% CI 74%-90%) and 58% (95% CI 48%-68%), respectively. The median overall survival (OS) was 25.8 (95% CI 12.8-not estimable) months, and the 5-year OS rate was 42.6% (95% CI 32.8%-51.9%). No new treatment-related adverse events were observed.

Study details: This 5-year follow-up analysis of the ZUMA-1 study phase 2 included 101 adult patients with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) who received lymphodepleting chemotherapy followed by axi-cel infusion.

Disclosures: This study was funded by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite. Seven authors declared being former or current employees of or holding stocks or having other ownership interests in Kite.

Source: Neelapu SS et al. 5-Year follow-up supports curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1). Blood. 2023 (Feb 23). Doi: 10.1182/blood.2022018893

Key clinical point: Axicabtagene ciloleucel (axi-cel) led to a durable response and long-term survival in patients with refractory large B-cell lymphoma (LBCL), with no new safety signals.

Major finding: At a median follow-up of 63.1 months from infusion, the objective and complete response rates were 83% (95% CI 74%-90%) and 58% (95% CI 48%-68%), respectively. The median overall survival (OS) was 25.8 (95% CI 12.8-not estimable) months, and the 5-year OS rate was 42.6% (95% CI 32.8%-51.9%). No new treatment-related adverse events were observed.

Study details: This 5-year follow-up analysis of the ZUMA-1 study phase 2 included 101 adult patients with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) who received lymphodepleting chemotherapy followed by axi-cel infusion.

Disclosures: This study was funded by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite. Seven authors declared being former or current employees of or holding stocks or having other ownership interests in Kite.

Source: Neelapu SS et al. 5-Year follow-up supports curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1). Blood. 2023 (Feb 23). Doi: 10.1182/blood.2022018893

Key clinical point: Axicabtagene ciloleucel (axi-cel) led to a durable response and long-term survival in patients with refractory large B-cell lymphoma (LBCL), with no new safety signals.

Major finding: At a median follow-up of 63.1 months from infusion, the objective and complete response rates were 83% (95% CI 74%-90%) and 58% (95% CI 48%-68%), respectively. The median overall survival (OS) was 25.8 (95% CI 12.8-not estimable) months, and the 5-year OS rate was 42.6% (95% CI 32.8%-51.9%). No new treatment-related adverse events were observed.

Study details: This 5-year follow-up analysis of the ZUMA-1 study phase 2 included 101 adult patients with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) who received lymphodepleting chemotherapy followed by axi-cel infusion.

Disclosures: This study was funded by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite. Seven authors declared being former or current employees of or holding stocks or having other ownership interests in Kite.

Source: Neelapu SS et al. 5-Year follow-up supports curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1). Blood. 2023 (Feb 23). Doi: 10.1182/blood.2022018893

Key clinical point: Venetoclax resulted in a good overall response rate (ORR) but short progression-free survival (PFS) in high-risk and heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 16.4 months, patients receiving venetoclax without or with other agents had a median PFS and overall survival of 3.7 (95% CI 2.3-5.6) months and 12.5 (95% CI,6.2-28.2) months, respectively, and an ORR of 40%.

Study details: The data come from a multicenter retrospective study including 81 adult patients with relapsed/refractory MCL, most being heavily pretreated (median of three prior treatments) and having high-risk features including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents.

Disclosures: This study was partly supported by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and others. Some authors reported ties with various organizations.

Source: Sawalha Y et al. A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv. 2023 (Feb 21). Doi: 10.1182/bloodadvances.2022008916

Key clinical point: Venetoclax resulted in a good overall response rate (ORR) but short progression-free survival (PFS) in high-risk and heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 16.4 months, patients receiving venetoclax without or with other agents had a median PFS and overall survival of 3.7 (95% CI 2.3-5.6) months and 12.5 (95% CI,6.2-28.2) months, respectively, and an ORR of 40%.

Study details: The data come from a multicenter retrospective study including 81 adult patients with relapsed/refractory MCL, most being heavily pretreated (median of three prior treatments) and having high-risk features including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents.

Disclosures: This study was partly supported by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and others. Some authors reported ties with various organizations.

Source: Sawalha Y et al. A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv. 2023 (Feb 21). Doi: 10.1182/bloodadvances.2022008916

Key clinical point: Venetoclax resulted in a good overall response rate (ORR) but short progression-free survival (PFS) in high-risk and heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 16.4 months, patients receiving venetoclax without or with other agents had a median PFS and overall survival of 3.7 (95% CI 2.3-5.6) months and 12.5 (95% CI,6.2-28.2) months, respectively, and an ORR of 40%.

Study details: The data come from a multicenter retrospective study including 81 adult patients with relapsed/refractory MCL, most being heavily pretreated (median of three prior treatments) and having high-risk features including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents.

Disclosures: This study was partly supported by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and others. Some authors reported ties with various organizations.

Source: Sawalha Y et al. A multicenter analysis of the outcomes with venetoclax in patients with relapsed mantle cell lymphoma. Blood Adv. 2023 (Feb 21). Doi: 10.1182/bloodadvances.2022008916

Key clinical point: Brexucabtagene autoleucel (brexu-cel) demonstrated promising efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL) in real-world practice, which is consistent with that reported in the ZUMA-2 trial.

Major finding: At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. The grade ≥3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively.

Study details: This multicenter retrospective study included 189 patients with relapsed or refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion.

Disclosures: This study was sponsored by a US National Cancer Institute cancer support grant. Some authors reported ties with various organizations.

Source: Wang Y et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023 (Feb 8). Doi: 10.1200/JCO.22.01797

Key clinical point: Brexucabtagene autoleucel (brexu-cel) demonstrated promising efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL) in real-world practice, which is consistent with that reported in the ZUMA-2 trial.

Major finding: At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. The grade ≥3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively.

Study details: This multicenter retrospective study included 189 patients with relapsed or refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion.

Disclosures: This study was sponsored by a US National Cancer Institute cancer support grant. Some authors reported ties with various organizations.

Source: Wang Y et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023 (Feb 8). Doi: 10.1200/JCO.22.01797

Key clinical point: Brexucabtagene autoleucel (brexu-cel) demonstrated promising efficacy and a favorable safety profile in patients with relapsed or refractory mantle cell lymphoma (MCL) in real-world practice, which is consistent with that reported in the ZUMA-2 trial.

Major finding: At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. The grade ≥3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively.

Study details: This multicenter retrospective study included 189 patients with relapsed or refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion.

Disclosures: This study was sponsored by a US National Cancer Institute cancer support grant. Some authors reported ties with various organizations.

Source: Wang Y et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023 (Feb 8). Doi: 10.1200/JCO.22.01797

NEW ORLEANS – Among individuals who were surveyed at a health fair, most of whom were persons of color, 57% self-reported having sensitive skin.

Respondents also reported high rates of reactions to skin care products marketed for sensitive skin, and most said they had visited a dermatologist about their condition.

Those are among the key findings of a pilot study designed to assess the prevalence, symptom burden, and behaviors of self-identified persons of color with sensitive skin, which senior author Adam Friedman, MD, and colleagues defined as a subjective syndrome of cutaneous hyperreactivity to otherwise innocuous stimuli. “Improved understanding of sensitive skin is essential, and we encourage additional research into pathophysiology and creating a consensus definition for sensitive skin,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. The findings were also reported online in JAAD International.

In May of 2022, Dr. Friedman, first author Erika McCormick, a 4th-year medical student at George Washington University, and colleagues invited individuals attending a community health fair in an undeserved area of Washington, to complete the Sensitive Scale-10 (SS-10) and to answer other questions after receiving a brief education about sensitive skin. Of the 58 respondents, 78% were female, and 86% self-identified as a person of color.

“Our study population predominantly self-identified as Black, which only represents one piece of those who would be characterized as persons of color,” Dr. Friedman said. “That said, improved representation of both our study population, and furthermore persons of color, in all aspects of dermatology research is crucial to at a minimum ensure generalizability of findings to the U.S. population, and research on sensitive skin is but one component of this.”

Nearly two-thirds of all respondents (63.8%) reported having an underlying skin condition, most commonly acne (21%), eczema (17%), and rosacea (6%). More than half (57%) reported sensitive skin, 27% of whom reported no other skin disease. Individuals with sensitive skin had higher mean SS-10 scores, compared with those with nonsensitive skin (14.61 vs. 4.32; P = .002) and burning was the main symptom among those with sensitive skin (56%), followed by itch (50%), redness (39%), dryness (39%) and pain (17%).

Compared with those who did not meet criteria for sensitive skin, those who did were more likely to report a personal history of allergy (56.25% vs. 8.33%; P = .0002) and were nearly seven times more likely to have seen a dermatologist about their concerns (odds ratio, 6.857; P = .0012).

In other findings limited to respondents with sensitive skin, 72% who reported reactions to general consumer skin care products also reported reacting to products marketed for sensitive skin, and 94% reported reactivity to at least one trigger, most commonly extreme temperatures (34%), stress (34%), sweat (33%), sun exposure (29%), and diet (28%). “We were particularly surprised by the high rates of reactivity to skin care products designed for and marketed to those suffering with sensitive skin,” Ms. McCormick told this news organization. “Importantly, there is currently no federal or legal standard regulating ingredients in products marketed for sensitive skin, and many products lack testing in sensitive skin specifically. Our data suggest an opportunity for improvement of sensitive skin care.”

She acknowledged certain limitations of the study, including its small sample size. “Reconducting this survey in a larger population will help validate our findings,” she said.

The research was supported by two independent research grants from Galderma: one supporting Ms. McCormick with a Sensitive Skin Research Fellowship and the other a Sensitive Skin Research Acceleration Fund. Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Among individuals who were surveyed at a health fair, most of whom were persons of color, 57% self-reported having sensitive skin.

Respondents also reported high rates of reactions to skin care products marketed for sensitive skin, and most said they had visited a dermatologist about their condition.

Those are among the key findings of a pilot study designed to assess the prevalence, symptom burden, and behaviors of self-identified persons of color with sensitive skin, which senior author Adam Friedman, MD, and colleagues defined as a subjective syndrome of cutaneous hyperreactivity to otherwise innocuous stimuli. “Improved understanding of sensitive skin is essential, and we encourage additional research into pathophysiology and creating a consensus definition for sensitive skin,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. The findings were also reported online in JAAD International.

In May of 2022, Dr. Friedman, first author Erika McCormick, a 4th-year medical student at George Washington University, and colleagues invited individuals attending a community health fair in an undeserved area of Washington, to complete the Sensitive Scale-10 (SS-10) and to answer other questions after receiving a brief education about sensitive skin. Of the 58 respondents, 78% were female, and 86% self-identified as a person of color.

“Our study population predominantly self-identified as Black, which only represents one piece of those who would be characterized as persons of color,” Dr. Friedman said. “That said, improved representation of both our study population, and furthermore persons of color, in all aspects of dermatology research is crucial to at a minimum ensure generalizability of findings to the U.S. population, and research on sensitive skin is but one component of this.”

Nearly two-thirds of all respondents (63.8%) reported having an underlying skin condition, most commonly acne (21%), eczema (17%), and rosacea (6%). More than half (57%) reported sensitive skin, 27% of whom reported no other skin disease. Individuals with sensitive skin had higher mean SS-10 scores, compared with those with nonsensitive skin (14.61 vs. 4.32; P = .002) and burning was the main symptom among those with sensitive skin (56%), followed by itch (50%), redness (39%), dryness (39%) and pain (17%).

Compared with those who did not meet criteria for sensitive skin, those who did were more likely to report a personal history of allergy (56.25% vs. 8.33%; P = .0002) and were nearly seven times more likely to have seen a dermatologist about their concerns (odds ratio, 6.857; P = .0012).

In other findings limited to respondents with sensitive skin, 72% who reported reactions to general consumer skin care products also reported reacting to products marketed for sensitive skin, and 94% reported reactivity to at least one trigger, most commonly extreme temperatures (34%), stress (34%), sweat (33%), sun exposure (29%), and diet (28%). “We were particularly surprised by the high rates of reactivity to skin care products designed for and marketed to those suffering with sensitive skin,” Ms. McCormick told this news organization. “Importantly, there is currently no federal or legal standard regulating ingredients in products marketed for sensitive skin, and many products lack testing in sensitive skin specifically. Our data suggest an opportunity for improvement of sensitive skin care.”

She acknowledged certain limitations of the study, including its small sample size. “Reconducting this survey in a larger population will help validate our findings,” she said.

The research was supported by two independent research grants from Galderma: one supporting Ms. McCormick with a Sensitive Skin Research Fellowship and the other a Sensitive Skin Research Acceleration Fund. Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Among individuals who were surveyed at a health fair, most of whom were persons of color, 57% self-reported having sensitive skin.

Respondents also reported high rates of reactions to skin care products marketed for sensitive skin, and most said they had visited a dermatologist about their condition.

Those are among the key findings of a pilot study designed to assess the prevalence, symptom burden, and behaviors of self-identified persons of color with sensitive skin, which senior author Adam Friedman, MD, and colleagues defined as a subjective syndrome of cutaneous hyperreactivity to otherwise innocuous stimuli. “Improved understanding of sensitive skin is essential, and we encourage additional research into pathophysiology and creating a consensus definition for sensitive skin,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said in an interview in advance of the annual meeting of the American Academy of Dermatology, where the study was presented during an e-poster session. The findings were also reported online in JAAD International.

In May of 2022, Dr. Friedman, first author Erika McCormick, a 4th-year medical student at George Washington University, and colleagues invited individuals attending a community health fair in an undeserved area of Washington, to complete the Sensitive Scale-10 (SS-10) and to answer other questions after receiving a brief education about sensitive skin. Of the 58 respondents, 78% were female, and 86% self-identified as a person of color.

“Our study population predominantly self-identified as Black, which only represents one piece of those who would be characterized as persons of color,” Dr. Friedman said. “That said, improved representation of both our study population, and furthermore persons of color, in all aspects of dermatology research is crucial to at a minimum ensure generalizability of findings to the U.S. population, and research on sensitive skin is but one component of this.”

Nearly two-thirds of all respondents (63.8%) reported having an underlying skin condition, most commonly acne (21%), eczema (17%), and rosacea (6%). More than half (57%) reported sensitive skin, 27% of whom reported no other skin disease. Individuals with sensitive skin had higher mean SS-10 scores, compared with those with nonsensitive skin (14.61 vs. 4.32; P = .002) and burning was the main symptom among those with sensitive skin (56%), followed by itch (50%), redness (39%), dryness (39%) and pain (17%).

Compared with those who did not meet criteria for sensitive skin, those who did were more likely to report a personal history of allergy (56.25% vs. 8.33%; P = .0002) and were nearly seven times more likely to have seen a dermatologist about their concerns (odds ratio, 6.857; P = .0012).

In other findings limited to respondents with sensitive skin, 72% who reported reactions to general consumer skin care products also reported reacting to products marketed for sensitive skin, and 94% reported reactivity to at least one trigger, most commonly extreme temperatures (34%), stress (34%), sweat (33%), sun exposure (29%), and diet (28%). “We were particularly surprised by the high rates of reactivity to skin care products designed for and marketed to those suffering with sensitive skin,” Ms. McCormick told this news organization. “Importantly, there is currently no federal or legal standard regulating ingredients in products marketed for sensitive skin, and many products lack testing in sensitive skin specifically. Our data suggest an opportunity for improvement of sensitive skin care.”

She acknowledged certain limitations of the study, including its small sample size. “Reconducting this survey in a larger population will help validate our findings,” she said.

The research was supported by two independent research grants from Galderma: one supporting Ms. McCormick with a Sensitive Skin Research Fellowship and the other a Sensitive Skin Research Acceleration Fund. Dr. Friedman reported having no relevant disclosures.

NEW ORLEANS – Treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the SGLT2 inhibitor dapagliflozin (Farxiga) for 24 weeks produced significant and beneficial reductions in left-heart filling pressures in a mechanistic, randomized clinical study.

The findings “provide new insight into the mechanisms underlying the favorable clinical effects of dapagliflozin in patients with HFpEF,” Barry A. Borlaug, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. “Elevations in left heart filling pressures at rest and during exercise are fundamental pathophysiologic features of HFpEF,” he noted.

Results from prior studies documented the benefit of dapagliflozin for improving clinical outcomes in patients with HFpEF in the DELIVER trial, and for the related sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in the EMPEROR-Preserved trial. The new findings presented by Dr. Borlaug provide evidence from a placebo-controlled, prospective study for one way by which these SGLT2 inhibitors exert this benefit in patients with HFpEF.

The results of his single-center study showed that, in patients with HFpEF who also exhibited “severe” elevations in pulmonary capillary wedge pressure (PCWP) during exercise, 24 weeks of treatment with dapagliflozin led to a significant reduction in PCWP during exercise. The treatment produced an average 6.1–mm Hg drop from baseline compared with control patients who received placebo. A similar pattern occurred when these patients were at rest, when dapagliflozin treatment linked with a significant average reduction in PCWP from baseline of 3.5 mm Hg compared with controls.
 

Improving a ‘specific and fundamental’ feature of HFpEF

“This fantastic study looked at one of the fundamental aspects of HFpEF,” said John R. Teerlink, MD, designated discussant for the study. “You’ve shown that dapagliflozin targets a specific and fundamental” manifestation of HFpEF by lowering PCWP, said Dr. Teerlink, director of Heart Failure at the San Francisco Veterans Affairs Medical Center.

However, Dr. Teerlink added, the study did not directly address the related question of what physiologic action of dapagliflozin produces this notable drop in PCWP.

“We’re just starting to look at that,” replied Dr. Borlaug, a cardiologist and professor at the Mayo Clinic in Rochester, Minn.

He reported finding an intriguing correlate in the current study linked to the cut in PCWP with dapagliflozin treatment. The SGLT2 inhibitor at a standard daily 10-mg dose produced an average 3.5-kg drop in body weight in the dapagliflozin-treated patients that significantly linked with the changes in PCWP both at rest and during exercise. Dapagliflozin-treated patients also showed a significant reduction from their baseline plasma volume compared with placebo-treated patients, but this “poorly correlated” with the dapagliflozin-linked cuts in PCWP, Dr. Borlaug said.

“I don’t think this means weight loss is the cause of the hemodynamic benefit, but maybe it’s an indicator. When patients [with HFpEF] lose weight, they are in a metabolic state that leads to good changes in hemodynamics,” he suggested. “My guess is that there is probably a combination of many different little things [caused by dapagliflozin treatment of patients with HFpEF] that together result in the 20%-25% relative improvement we see in filling pressure.”
 

An ‘obese, cardiometabolic’ HFpEF phenotype

The study enrolled patients with HFpEF and a left ventricular ejection fraction of at least 50%, a New York Heart Association functional class of 2 or 3, and a PCWP during exercise of at least 25 mm Hg. Of the 37 evaluable patients, about two-thirds of the patients were women, more than two-thirds were in functional class 3, about 70% were obese, and their average ejection fraction was about 62%. The study excluded patients with HFpEF who also had type 1 diabetes, cardiomyopathy, pericardial disease, or other causes of dyspnea or heart failure.

Dr. Teerlink asked about the generalizability of the findings, as the study cohort seemed to differ in certain respects from the patients enrolled in the DELIVER trial, and because of the many apparently distinct patient phenotypes that exist within the scope of HFpEF.

An “obese, cardiometabolic phenotype” predominated the study cohort, Dr. Borlaug said. “The patients we enrolled look like the HFpEF patients seen in U.S. clinics.” However, he added that “in reality, many [HFpEF phenotypes] coexist in one patient. It’s not that simple,” that every patient with HFpEF can be categorized into a single HFpEF phenotype.

The researchers monitored PCWP invasively with high-fidelity micromanometer catheters.

The study was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Borlaug has received research funding from AstraZeneca, as well as from Corvia, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax. Dr. Teerlink has had financial relationships with AstraZeneca, as well as with Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics.

NEW ORLEANS – Treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the SGLT2 inhibitor dapagliflozin (Farxiga) for 24 weeks produced significant and beneficial reductions in left-heart filling pressures in a mechanistic, randomized clinical study.

The findings “provide new insight into the mechanisms underlying the favorable clinical effects of dapagliflozin in patients with HFpEF,” Barry A. Borlaug, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. “Elevations in left heart filling pressures at rest and during exercise are fundamental pathophysiologic features of HFpEF,” he noted.

Results from prior studies documented the benefit of dapagliflozin for improving clinical outcomes in patients with HFpEF in the DELIVER trial, and for the related sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in the EMPEROR-Preserved trial. The new findings presented by Dr. Borlaug provide evidence from a placebo-controlled, prospective study for one way by which these SGLT2 inhibitors exert this benefit in patients with HFpEF.

The results of his single-center study showed that, in patients with HFpEF who also exhibited “severe” elevations in pulmonary capillary wedge pressure (PCWP) during exercise, 24 weeks of treatment with dapagliflozin led to a significant reduction in PCWP during exercise. The treatment produced an average 6.1–mm Hg drop from baseline compared with control patients who received placebo. A similar pattern occurred when these patients were at rest, when dapagliflozin treatment linked with a significant average reduction in PCWP from baseline of 3.5 mm Hg compared with controls.
 

Improving a ‘specific and fundamental’ feature of HFpEF

“This fantastic study looked at one of the fundamental aspects of HFpEF,” said John R. Teerlink, MD, designated discussant for the study. “You’ve shown that dapagliflozin targets a specific and fundamental” manifestation of HFpEF by lowering PCWP, said Dr. Teerlink, director of Heart Failure at the San Francisco Veterans Affairs Medical Center.

However, Dr. Teerlink added, the study did not directly address the related question of what physiologic action of dapagliflozin produces this notable drop in PCWP.

“We’re just starting to look at that,” replied Dr. Borlaug, a cardiologist and professor at the Mayo Clinic in Rochester, Minn.

He reported finding an intriguing correlate in the current study linked to the cut in PCWP with dapagliflozin treatment. The SGLT2 inhibitor at a standard daily 10-mg dose produced an average 3.5-kg drop in body weight in the dapagliflozin-treated patients that significantly linked with the changes in PCWP both at rest and during exercise. Dapagliflozin-treated patients also showed a significant reduction from their baseline plasma volume compared with placebo-treated patients, but this “poorly correlated” with the dapagliflozin-linked cuts in PCWP, Dr. Borlaug said.

“I don’t think this means weight loss is the cause of the hemodynamic benefit, but maybe it’s an indicator. When patients [with HFpEF] lose weight, they are in a metabolic state that leads to good changes in hemodynamics,” he suggested. “My guess is that there is probably a combination of many different little things [caused by dapagliflozin treatment of patients with HFpEF] that together result in the 20%-25% relative improvement we see in filling pressure.”
 

An ‘obese, cardiometabolic’ HFpEF phenotype

The study enrolled patients with HFpEF and a left ventricular ejection fraction of at least 50%, a New York Heart Association functional class of 2 or 3, and a PCWP during exercise of at least 25 mm Hg. Of the 37 evaluable patients, about two-thirds of the patients were women, more than two-thirds were in functional class 3, about 70% were obese, and their average ejection fraction was about 62%. The study excluded patients with HFpEF who also had type 1 diabetes, cardiomyopathy, pericardial disease, or other causes of dyspnea or heart failure.

Dr. Teerlink asked about the generalizability of the findings, as the study cohort seemed to differ in certain respects from the patients enrolled in the DELIVER trial, and because of the many apparently distinct patient phenotypes that exist within the scope of HFpEF.

An “obese, cardiometabolic phenotype” predominated the study cohort, Dr. Borlaug said. “The patients we enrolled look like the HFpEF patients seen in U.S. clinics.” However, he added that “in reality, many [HFpEF phenotypes] coexist in one patient. It’s not that simple,” that every patient with HFpEF can be categorized into a single HFpEF phenotype.

The researchers monitored PCWP invasively with high-fidelity micromanometer catheters.

The study was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Borlaug has received research funding from AstraZeneca, as well as from Corvia, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax. Dr. Teerlink has had financial relationships with AstraZeneca, as well as with Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics.

NEW ORLEANS – Treatment of patients with heart failure with preserved ejection fraction (HFpEF) with the SGLT2 inhibitor dapagliflozin (Farxiga) for 24 weeks produced significant and beneficial reductions in left-heart filling pressures in a mechanistic, randomized clinical study.

The findings “provide new insight into the mechanisms underlying the favorable clinical effects of dapagliflozin in patients with HFpEF,” Barry A. Borlaug, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. “Elevations in left heart filling pressures at rest and during exercise are fundamental pathophysiologic features of HFpEF,” he noted.

Results from prior studies documented the benefit of dapagliflozin for improving clinical outcomes in patients with HFpEF in the DELIVER trial, and for the related sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (Jardiance) in the EMPEROR-Preserved trial. The new findings presented by Dr. Borlaug provide evidence from a placebo-controlled, prospective study for one way by which these SGLT2 inhibitors exert this benefit in patients with HFpEF.

The results of his single-center study showed that, in patients with HFpEF who also exhibited “severe” elevations in pulmonary capillary wedge pressure (PCWP) during exercise, 24 weeks of treatment with dapagliflozin led to a significant reduction in PCWP during exercise. The treatment produced an average 6.1–mm Hg drop from baseline compared with control patients who received placebo. A similar pattern occurred when these patients were at rest, when dapagliflozin treatment linked with a significant average reduction in PCWP from baseline of 3.5 mm Hg compared with controls.
 

Improving a ‘specific and fundamental’ feature of HFpEF

“This fantastic study looked at one of the fundamental aspects of HFpEF,” said John R. Teerlink, MD, designated discussant for the study. “You’ve shown that dapagliflozin targets a specific and fundamental” manifestation of HFpEF by lowering PCWP, said Dr. Teerlink, director of Heart Failure at the San Francisco Veterans Affairs Medical Center.

However, Dr. Teerlink added, the study did not directly address the related question of what physiologic action of dapagliflozin produces this notable drop in PCWP.

“We’re just starting to look at that,” replied Dr. Borlaug, a cardiologist and professor at the Mayo Clinic in Rochester, Minn.

He reported finding an intriguing correlate in the current study linked to the cut in PCWP with dapagliflozin treatment. The SGLT2 inhibitor at a standard daily 10-mg dose produced an average 3.5-kg drop in body weight in the dapagliflozin-treated patients that significantly linked with the changes in PCWP both at rest and during exercise. Dapagliflozin-treated patients also showed a significant reduction from their baseline plasma volume compared with placebo-treated patients, but this “poorly correlated” with the dapagliflozin-linked cuts in PCWP, Dr. Borlaug said.

“I don’t think this means weight loss is the cause of the hemodynamic benefit, but maybe it’s an indicator. When patients [with HFpEF] lose weight, they are in a metabolic state that leads to good changes in hemodynamics,” he suggested. “My guess is that there is probably a combination of many different little things [caused by dapagliflozin treatment of patients with HFpEF] that together result in the 20%-25% relative improvement we see in filling pressure.”
 

An ‘obese, cardiometabolic’ HFpEF phenotype

The study enrolled patients with HFpEF and a left ventricular ejection fraction of at least 50%, a New York Heart Association functional class of 2 or 3, and a PCWP during exercise of at least 25 mm Hg. Of the 37 evaluable patients, about two-thirds of the patients were women, more than two-thirds were in functional class 3, about 70% were obese, and their average ejection fraction was about 62%. The study excluded patients with HFpEF who also had type 1 diabetes, cardiomyopathy, pericardial disease, or other causes of dyspnea or heart failure.

Dr. Teerlink asked about the generalizability of the findings, as the study cohort seemed to differ in certain respects from the patients enrolled in the DELIVER trial, and because of the many apparently distinct patient phenotypes that exist within the scope of HFpEF.

An “obese, cardiometabolic phenotype” predominated the study cohort, Dr. Borlaug said. “The patients we enrolled look like the HFpEF patients seen in U.S. clinics.” However, he added that “in reality, many [HFpEF phenotypes] coexist in one patient. It’s not that simple,” that every patient with HFpEF can be categorized into a single HFpEF phenotype.

The researchers monitored PCWP invasively with high-fidelity micromanometer catheters.

The study was sponsored by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. Borlaug has received research funding from AstraZeneca, as well as from Corvia, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax. Dr. Teerlink has had financial relationships with AstraZeneca, as well as with Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Servier, and Windtree Therapeutics.