Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

Key clinical point: Ibrutinib continued to benefit most treatment-naive patients (58%) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the RESONATE-2 study for ≥5 years, irrespective of baseline characteristics.

Major finding: At a median follow-up of 89.2 months, the median progression-free survival (PFS) and overall survival (OS) were not reached; the 7-year PFS and OS rates were 82% and 94%, respectively. Complete response rates increased from 10% at 1 year to 42% at 5 years and 46% at 7 years. No new safety signals were observed.

Study details: This study analyzed the data of 79 treatment-naive patients aged ≥65 years with CLL or SLL who were randomly assigned to receive ibrutinib in the phase 3 RESONATE-2 trial and its extension study and had continued the treatment for ≥5 years.

Disclosures: This study was sponsored by Pharmacyclics LLC, an AbbVie Company. Some authors reported ties with various organizations, including Pharmacyclics. Two authors declared being employees of, holding stocks in, or having other ownership interests in Pharmacyclics/AbbVie.

Source: Woyach JA et al. Characteristics and clinical outcomes of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma receiving ibrutinib for ≥5 years in the RESONATE-2 study. Cancers (Basel). 2023;15(2):507 (Jan 13). Doi: 10.3390/cancers15020507

Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

Key clinical point: Autologous stem cell transplantation (ASCT) leads to high durable remission rates in patients with relapsed follicular lymphoma (FL), with the functional cure rate elucidated by long-term follow-up being >50%.

Major finding: At a median follow-up of 12.5 years, the 12-year time-to-progression (TTP), time-to-next-treatment, progression-free survival, and overall survival rates were 57% (95% CI 49%-65%), 61% (95% CI 52%-69%), 51% (95% CI 42%-59%), and 69% (95% CI 60%-76%), respectively. The TTP curve achieved a plateau at 57% starting 9 years after ASCT with no relapses after this timepoint; 10 patients remained alive without recurrence for ≥20 years after ASCT.

Study details: This retrospective multicenter study included 162 adult patients with relapsed FL who underwent ASCT.

Disclosures: This study did not receive any funding. Some authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Long-term follow-up demonstrates curative potential of autologous stem cell transplantation for relapsed follicular lymphoma. Br J Haematol. 2023 (Jan 10). Doi: 10.1111/bjh.18640

Key clinical point: Second-line lisocabtagene maraleucel (liso-cel) offers better efficacy over standard of care (SOC; platinum-based immunochemotherapy followed by high-dose chemotherapy+autologous stem cell transplantation [ASCT]) in chemotherapy-sensitive patients with relapsed/refractory large B-cell lymphoma (LBCL) along with a favorable safety profile.

Major finding: After a 17.5-month median follow-up, the liso-cel vs SOC group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low grade 3 cytokine release syndrome (1%) and neurological event (4%) rates.

Study details: This phase 3 study, TRANSFORM, included 184 adult patients with relapsed/refractory LBCL who were eligible for high-dose chemotherapy+ASCT and were randomly assigned to receive liso-cel (100×10⁶ chimeric antigen receptor-positive T cells) or three cycles of SOC.

Disclosures: This study was funded by Celgene, a Bristol-Myers Squibb Company. Some authors reported ties with various organizations, including Celgene. Three authors declared being employees of Celgene.

Source: Abramson JS et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of phase 3 TRANSFORM study. Blood. 2022 (Dec 21). Doi: 10.1182/blood.2022018730

Key clinical point: Second-line lisocabtagene maraleucel (liso-cel) offers better efficacy over standard of care (SOC; platinum-based immunochemotherapy followed by high-dose chemotherapy+autologous stem cell transplantation [ASCT]) in chemotherapy-sensitive patients with relapsed/refractory large B-cell lymphoma (LBCL) along with a favorable safety profile.

Major finding: After a 17.5-month median follow-up, the liso-cel vs SOC group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low grade 3 cytokine release syndrome (1%) and neurological event (4%) rates.

Study details: This phase 3 study, TRANSFORM, included 184 adult patients with relapsed/refractory LBCL who were eligible for high-dose chemotherapy+ASCT and were randomly assigned to receive liso-cel (100×10⁶ chimeric antigen receptor-positive T cells) or three cycles of SOC.

Disclosures: This study was funded by Celgene, a Bristol-Myers Squibb Company. Some authors reported ties with various organizations, including Celgene. Three authors declared being employees of Celgene.

Source: Abramson JS et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of phase 3 TRANSFORM study. Blood. 2022 (Dec 21). Doi: 10.1182/blood.2022018730

Key clinical point: Second-line lisocabtagene maraleucel (liso-cel) offers better efficacy over standard of care (SOC; platinum-based immunochemotherapy followed by high-dose chemotherapy+autologous stem cell transplantation [ASCT]) in chemotherapy-sensitive patients with relapsed/refractory large B-cell lymphoma (LBCL) along with a favorable safety profile.

Major finding: After a 17.5-month median follow-up, the liso-cel vs SOC group had significantly improved median event-free survival (hazard ratio [HR] 0.356; 95% CI 0.243-0.522), median progression-free survival (HR 0.400; P < .0001), and complete response rate (74% vs 43%; P < .0001), along with low grade 3 cytokine release syndrome (1%) and neurological event (4%) rates.

Study details: This phase 3 study, TRANSFORM, included 184 adult patients with relapsed/refractory LBCL who were eligible for high-dose chemotherapy+ASCT and were randomly assigned to receive liso-cel (100×10⁶ chimeric antigen receptor-positive T cells) or three cycles of SOC.

Disclosures: This study was funded by Celgene, a Bristol-Myers Squibb Company. Some authors reported ties with various organizations, including Celgene. Three authors declared being employees of Celgene.

Source: Abramson JS et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of phase 3 TRANSFORM study. Blood. 2022 (Dec 21). Doi: 10.1182/blood.2022018730

Key clinical point: Rituximab maintenance (RM) therapy after first-line bendamustine-rituximab (BR) or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improved overall survival and disease control in older patients with mantle cell lymphoma (MCL).

Major finding: Patients who did vs did not receive RM therapy had a significantly longer overall survival (adjusted hazard ratio [aHR] 0.53; 95% CI 0.34-0.82) and approximated progression-free survival (survival or free of second-line therapy; aHR 0.51; 95% CI 0.36-0.72).

Study details: This real-world study included 131 propensity-score matched pairs of autologous stem cell transplant-ineligible patients aged ≥66 years with MCL who did and did not receive RM after first-line treatment with BR or R-CHOP.

Disclosures: This study did not receive any financial support. No information on conflicts of interest was reported.

Source: Di M et al. Treatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: A population-based analysis. Haematologica. 2023 (Jan 19). Doi: 10.3324/haematol.2022.282252

Key clinical point: Rituximab maintenance (RM) therapy after first-line bendamustine-rituximab (BR) or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improved overall survival and disease control in older patients with mantle cell lymphoma (MCL).

Major finding: Patients who did vs did not receive RM therapy had a significantly longer overall survival (adjusted hazard ratio [aHR] 0.53; 95% CI 0.34-0.82) and approximated progression-free survival (survival or free of second-line therapy; aHR 0.51; 95% CI 0.36-0.72).

Study details: This real-world study included 131 propensity-score matched pairs of autologous stem cell transplant-ineligible patients aged ≥66 years with MCL who did and did not receive RM after first-line treatment with BR or R-CHOP.

Disclosures: This study did not receive any financial support. No information on conflicts of interest was reported.

Source: Di M et al. Treatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: A population-based analysis. Haematologica. 2023 (Jan 19). Doi: 10.3324/haematol.2022.282252

Key clinical point: Rituximab maintenance (RM) therapy after first-line bendamustine-rituximab (BR) or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) improved overall survival and disease control in older patients with mantle cell lymphoma (MCL).

Major finding: Patients who did vs did not receive RM therapy had a significantly longer overall survival (adjusted hazard ratio [aHR] 0.53; 95% CI 0.34-0.82) and approximated progression-free survival (survival or free of second-line therapy; aHR 0.51; 95% CI 0.36-0.72).

Study details: This real-world study included 131 propensity-score matched pairs of autologous stem cell transplant-ineligible patients aged ≥66 years with MCL who did and did not receive RM after first-line treatment with BR or R-CHOP.

Disclosures: This study did not receive any financial support. No information on conflicts of interest was reported.

Source: Di M et al. Treatment patterns and real-world effectiveness of rituximab maintenance in older patients with mantle cell lymphoma: A population-based analysis. Haematologica. 2023 (Jan 19). Doi: 10.3324/haematol.2022.282252

Key clinical point: In the real-world setting, dose reductions and therapy delays are more common among elderly vs younger patients receiving first-line bendamustine-rituximab (BR) for indolent non-Hodgkin's lymphoma (iNHL) or mantle cell lymphoma (MCL); however, the efficacy and safety of BR is unaffected across age groups.

Major finding: At a median follow-up of 42 months, the elderly vs younger patient group had a significantly lower proportion of patients receiving full doses of bendamustine (54% vs 79.5%; P < .001) and higher treatment delay rate (54% vs 43.2%; P < .001) but similar disease-free survival (P = .069). The number of all-grade adverse events per patient was similar between the groups across each BR cycle.

Study details: This retrospective observational cohort study included 201 patients (elderly [≥70 years] n = 113 or younger [18-70 years] n = 88) with iNHL or MCL who received BR therapy.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kotchetkov R et al. Bendamustine and rituximab is well-tolerated and efficient in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma in elderly: A single center observational study. Int J Cancer. 2022 (Dec 22). Doi: 10.1002/ijc.34412

Key clinical point: In the real-world setting, dose reductions and therapy delays are more common among elderly vs younger patients receiving first-line bendamustine-rituximab (BR) for indolent non-Hodgkin's lymphoma (iNHL) or mantle cell lymphoma (MCL); however, the efficacy and safety of BR is unaffected across age groups.

Major finding: At a median follow-up of 42 months, the elderly vs younger patient group had a significantly lower proportion of patients receiving full doses of bendamustine (54% vs 79.5%; P < .001) and higher treatment delay rate (54% vs 43.2%; P < .001) but similar disease-free survival (P = .069). The number of all-grade adverse events per patient was similar between the groups across each BR cycle.

Study details: This retrospective observational cohort study included 201 patients (elderly [≥70 years] n = 113 or younger [18-70 years] n = 88) with iNHL or MCL who received BR therapy.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kotchetkov R et al. Bendamustine and rituximab is well-tolerated and efficient in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma in elderly: A single center observational study. Int J Cancer. 2022 (Dec 22). Doi: 10.1002/ijc.34412

Key clinical point: In the real-world setting, dose reductions and therapy delays are more common among elderly vs younger patients receiving first-line bendamustine-rituximab (BR) for indolent non-Hodgkin's lymphoma (iNHL) or mantle cell lymphoma (MCL); however, the efficacy and safety of BR is unaffected across age groups.

Major finding: At a median follow-up of 42 months, the elderly vs younger patient group had a significantly lower proportion of patients receiving full doses of bendamustine (54% vs 79.5%; P < .001) and higher treatment delay rate (54% vs 43.2%; P < .001) but similar disease-free survival (P = .069). The number of all-grade adverse events per patient was similar between the groups across each BR cycle.

Study details: This retrospective observational cohort study included 201 patients (elderly [≥70 years] n = 113 or younger [18-70 years] n = 88) with iNHL or MCL who received BR therapy.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Kotchetkov R et al. Bendamustine and rituximab is well-tolerated and efficient in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma in elderly: A single center observational study. Int J Cancer. 2022 (Dec 22). Doi: 10.1002/ijc.34412

Key clinical point: Fixed-duration glofitamab treatment led to durable complete responses and a grade ≥3 adverse event (AE) rate of >50% in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. The median time to a complete response was 42 (95% CI 42-44) days; 78% of patients with a complete response continued to be in remission at 12 months. The grade ≥3 AE rate was 62%.

Study details: This phase 2 part of a phase 1-2 study included 155 adult patients with relapsed/refractory DLBCL previously treated with ≥2 lines of therapy who received obinutuzumab pretreatment followed by fixed-duration glofitamab monotherapy for 12 cycles.

Disclosures: This study was funded by F. Hoffmann-La Roche. Some authors reported ties with various organizations, including F. Hoffmann-La Roche. Two authors declared being employees of and holding stock or stock options in F. Hoffmann-La Roche.

Source: Dickinson MJ et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231 (Dec 11). Doi: 10.1056/NEJMoa2206913

Key clinical point: Fixed-duration glofitamab treatment led to durable complete responses and a grade ≥3 adverse event (AE) rate of >50% in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. The median time to a complete response was 42 (95% CI 42-44) days; 78% of patients with a complete response continued to be in remission at 12 months. The grade ≥3 AE rate was 62%.

Study details: This phase 2 part of a phase 1-2 study included 155 adult patients with relapsed/refractory DLBCL previously treated with ≥2 lines of therapy who received obinutuzumab pretreatment followed by fixed-duration glofitamab monotherapy for 12 cycles.

Disclosures: This study was funded by F. Hoffmann-La Roche. Some authors reported ties with various organizations, including F. Hoffmann-La Roche. Two authors declared being employees of and holding stock or stock options in F. Hoffmann-La Roche.

Source: Dickinson MJ et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231 (Dec 11). Doi: 10.1056/NEJMoa2206913

Key clinical point: Fixed-duration glofitamab treatment led to durable complete responses and a grade ≥3 adverse event (AE) rate of >50% in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: At a median follow-up of 12.6 months, 39% (95% CI 32%-48%) and 52% (95% CI 43%-60%) of patients achieved complete and objective responses, respectively. The median time to a complete response was 42 (95% CI 42-44) days; 78% of patients with a complete response continued to be in remission at 12 months. The grade ≥3 AE rate was 62%.

Study details: This phase 2 part of a phase 1-2 study included 155 adult patients with relapsed/refractory DLBCL previously treated with ≥2 lines of therapy who received obinutuzumab pretreatment followed by fixed-duration glofitamab monotherapy for 12 cycles.

Disclosures: This study was funded by F. Hoffmann-La Roche. Some authors reported ties with various organizations, including F. Hoffmann-La Roche. Two authors declared being employees of and holding stock or stock options in F. Hoffmann-La Roche.

Source: Dickinson MJ et al. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2022;387(24):2220-2231 (Dec 11). Doi: 10.1056/NEJMoa2206913

Key clinical point: Compared with ibrutinib, zanubrutinib prolonged progression-free survival and demonstrated an improved safety profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Major finding: At a median follow-up of 29.6 months, the zanubrutinib vs ibrutinib group had a 35% decreased risk for progression or death (hazard ratio 0.65; P = .002) and a lower incidence of cardiac disorders (21.3% vs 29.6%) and adverse events leading to treatment discontinuation (15.4% vs 22.2%).

Study details: Findings are from the multicenter phase 3 ALPINE trial including 652 adult patients with relapsed or refractory CLL/SLL treated with ≥1 previous line of therapy who were randomly assigned to receive zanubrutinib (n = 327) or ibrutinib (n = 325).

Disclosures: This study was funded by BeiGene. Some authors reported ties with various organizations, including BeiGene. Six authors declared being employees of or holding stock or stock options in BeiGene.

Source: Brown JR et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2022;388(4):319-332 (Dec 13). Doi: 10.1056/NEJMoa2211582

Key clinical point: Compared with ibrutinib, zanubrutinib prolonged progression-free survival and demonstrated an improved safety profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Major finding: At a median follow-up of 29.6 months, the zanubrutinib vs ibrutinib group had a 35% decreased risk for progression or death (hazard ratio 0.65; P = .002) and a lower incidence of cardiac disorders (21.3% vs 29.6%) and adverse events leading to treatment discontinuation (15.4% vs 22.2%).

Study details: Findings are from the multicenter phase 3 ALPINE trial including 652 adult patients with relapsed or refractory CLL/SLL treated with ≥1 previous line of therapy who were randomly assigned to receive zanubrutinib (n = 327) or ibrutinib (n = 325).

Disclosures: This study was funded by BeiGene. Some authors reported ties with various organizations, including BeiGene. Six authors declared being employees of or holding stock or stock options in BeiGene.

Source: Brown JR et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2022;388(4):319-332 (Dec 13). Doi: 10.1056/NEJMoa2211582

Key clinical point: Compared with ibrutinib, zanubrutinib prolonged progression-free survival and demonstrated an improved safety profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Major finding: At a median follow-up of 29.6 months, the zanubrutinib vs ibrutinib group had a 35% decreased risk for progression or death (hazard ratio 0.65; P = .002) and a lower incidence of cardiac disorders (21.3% vs 29.6%) and adverse events leading to treatment discontinuation (15.4% vs 22.2%).

Study details: Findings are from the multicenter phase 3 ALPINE trial including 652 adult patients with relapsed or refractory CLL/SLL treated with ≥1 previous line of therapy who were randomly assigned to receive zanubrutinib (n = 327) or ibrutinib (n = 325).

Disclosures: This study was funded by BeiGene. Some authors reported ties with various organizations, including BeiGene. Six authors declared being employees of or holding stock or stock options in BeiGene.

Source: Brown JR et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2022;388(4):319-332 (Dec 13). Doi: 10.1056/NEJMoa2211582

Key clinical point: Rituximab+cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) compared with standard myeloablative radiochemotherapy and autologous stem cell transplantation (ASCT; R-CHOP arm), an alternating R-CHOP/rituximab+dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) induction therapy with high-dose cytarabine-containing myeloablative radiochemotherapy and ASCT (R-DHAP arm) led to longer time to treatment failure (TTF) and overall survival (OS) in patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer TTF (hazard ratio [HR] 0.59; P = .038) and OS (Mantle Cell Lymphoma International Prognostic Index+Ki-67-adjusted HR 0.60; P = .0066).

Study details: This long-term analysis of the phase 3 MCL Younger trial included 497 patients aged ≥18 to <66 years with previously untreated MCL who were randomly assigned to the R-CHOP (n = 249) or R-DHAP (n = 248) arm.

Disclosures: This study was supported by European Commission, Lymphoma Research Foundation, and Roche. Some authors reported ties with various organizations, including Roche.

Source: Hermine O et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized mantle cell lymphoma younger trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2022;41(3):479-484 (Dec 5). Doi: 10.1200/JCO.22.01780

Key clinical point: Rituximab+cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) compared with standard myeloablative radiochemotherapy and autologous stem cell transplantation (ASCT; R-CHOP arm), an alternating R-CHOP/rituximab+dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) induction therapy with high-dose cytarabine-containing myeloablative radiochemotherapy and ASCT (R-DHAP arm) led to longer time to treatment failure (TTF) and overall survival (OS) in patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer TTF (hazard ratio [HR] 0.59; P = .038) and OS (Mantle Cell Lymphoma International Prognostic Index+Ki-67-adjusted HR 0.60; P = .0066).

Study details: This long-term analysis of the phase 3 MCL Younger trial included 497 patients aged ≥18 to <66 years with previously untreated MCL who were randomly assigned to the R-CHOP (n = 249) or R-DHAP (n = 248) arm.

Disclosures: This study was supported by European Commission, Lymphoma Research Foundation, and Roche. Some authors reported ties with various organizations, including Roche.

Source: Hermine O et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized mantle cell lymphoma younger trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2022;41(3):479-484 (Dec 5). Doi: 10.1200/JCO.22.01780

Key clinical point: Rituximab+cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) compared with standard myeloablative radiochemotherapy and autologous stem cell transplantation (ASCT; R-CHOP arm), an alternating R-CHOP/rituximab+dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) induction therapy with high-dose cytarabine-containing myeloablative radiochemotherapy and ASCT (R-DHAP arm) led to longer time to treatment failure (TTF) and overall survival (OS) in patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer TTF (hazard ratio [HR] 0.59; P = .038) and OS (Mantle Cell Lymphoma International Prognostic Index+Ki-67-adjusted HR 0.60; P = .0066).

Study details: This long-term analysis of the phase 3 MCL Younger trial included 497 patients aged ≥18 to <66 years with previously untreated MCL who were randomly assigned to the R-CHOP (n = 249) or R-DHAP (n = 248) arm.

Disclosures: This study was supported by European Commission, Lymphoma Research Foundation, and Roche. Some authors reported ties with various organizations, including Roche.

Source: Hermine O et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized mantle cell lymphoma younger trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2022;41(3):479-484 (Dec 5). Doi: 10.1200/JCO.22.01780

Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Long-acting antiretroviral therapy (ART) for HIV involving injections every 1 or 2 months not only shows noninferiority to a standard daily oral treatment regimen, it also suppresses HIV even in patients who do not already have virologic suppression, as is typically required before initiation, results from two new studies suggest.

Meanwhile, a third study shows early promise of a long-acting ART regimen that could require injections only twice yearly.

“Instead of having the burden of taking a pill every day, patients with HIV can now have these choices of being able to forget about their treatment for up to 2 months at a time,” Moti N. Ramgopal, MD, first author of one of the three studies, said in a press conference at the Conference on Retroviruses and Opportunistic Infections. “My patients tell me that it’s game-changing for them.”
 

First head-to-head comparison

The injectable intramuscular combination of cabotegravir and rilpivirine, administered once every 1 or 2 months, is the first and only long-acting ART to be approved by the Food and Drug Administration for people with HIV. At the meeting, Dr. Ramgopal, from the Midway Immunology and Research Center in Fort Pierce, Fla., reported the results from the first head-to-head study comparing the regimen with the standard daily oral regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).

For the phase 3b SOLAR trial, adults with HIV who were already virologically suppressed and treated with daily B/FTC/TAF were randomly assigned to remain on the oral regimen (n = 223) or switch to the long-acting injections every 2 months, either with an oral lead-in (n = 173) or without a lead-in (n = 274).

The results after 12 months showed noninferiority between the groups, with 90% of the long-acting ART group and 93% in the oral daily pill group maintaining viral suppression, defined as plasma HIV-1 RNA less than 50 copies/mL.

Two patients (0.4%) receiving the long-acting ART in a modified-intention to treat and 3 (0.6%) in the intention-to-treat populations had confirmed virologic failure, and rates of adverse events leading to withdrawal were 6% with the long-acting ART group versus 1% with the oral treatment group.

As many as 90% of subjects reported preferring the long-acting ART over their previous oral therapy at the end of the study, and those in the long-acting group also reported significantly greater improvements in quality of life on the HIV Treatment Satisfaction Questionnaire status version compared with the oral therapy group at the end of the study (P < .001).

Prior to the randomization, as many as 47% of patients on the oral regimen reported “always” or “often” having psychosocial challenges with the daily therapy, including worries of having their HIV status revealed and forgetting to take the medication.

“These data demonstrate that [the long-acting regimen] addresses important unmet needs for people with HIV who are virally suppressed on oral daily HIV therapy, while improving the quality of life,” said Dr. Ramgopal.
 

Suppression at onset not necessarily required

For all of its benefits, a key caveat of the cabotegravir and rilpivirine long-acting regimen is that it is approved only for patients who have already achieved viral suppression and are currently on oral ART, meaning some of the people most in need, including those with unstable housing, mental illness, or substance abuse disorders, may be excluded.

To evaluate the therapy’s efficacy among those patient types, Monica Gandhi, MD, MPH, professor of medicine and associate division chief at the University of California, San Francisco, enrolled 133 participants between June 2021 and November 2022 at the Ward 86 HIV Clinic, a safety-net clinic in San Francisco, to initiate long-acting ART. Participants included 57 patients (43%) with untreated or unsuppressed HIV, and 76 who were virally suppressed on oral ART.

Of the whole study group, 66% reported unstable housing, 8% reported experiencing homelessness, 38% reported having a mental illness, and 33% reported substance use.

Although all of the subjects (100%) who started with viral suppression remained suppressed over the study’s 26-week follow-up, the rate of viral suppression at the study’s end was nearly as high – 55 of 57 subjects (96.5%) – among those who started long-acting ART without having viral suppression.

Of note, the overall rate of study participants who did not achieve or maintain viral suppression (1.5%) was consistent with rates reported in clinical trials of long-acting ART in people with HIV who had previously achieved viral suppression on daily oral ART.

“Our patient population does not look like the patient population that got enrolled in the clinical trials to determine the approval criteria for long-acting ART,” Dr. Gandhi said in presenting the findings.

“If 10% of the population carries 90% of the HIV virus – which we see in modeling – then we need innovations for this population if we want to end the HIV epidemic,” she added.

“We tried long-acting ART in our diverse, urban, low-income population and we saw very high virologic suppression rates equal to those that were seen in the clinical trials,” Dr. Ghandi reported. “This shows that long-acting ART, used creatively and used boldly, could really make a dent in the [efforts] to end the HIV epidemic movement.”

Commenting on the study in a press statement, Nora Volkow, MD, director of the National Institute on Drug Abuse, said “Dr. Gandhi and her team have made state-of-the-art HIV treatment finally available to people with unique challenges, like those who use drugs, and have found success.”

“This is the sweet spot for addressing HIV – thinking outside the box to deliver care in a way that meets people’s needs, even when that means it happens outside the clinic walls, by phone, or on neighborhood streets,” she said. “This can be done, but it requires creativity and resolve.”
 

Twice-yearly dosing option?

Looking ahead, an even more intriguing scenario of a long-acting ART requiring injections only once every 6 months may be getting closer to fruition. Researchers at CROI 2023 reported early but promising safety and efficacy results of an innovative combination of the first-in-class HIV-1 capsid inhibitor lenacapavir with teropavimab and zinlirvimab, two broadly neutralizing antibodies (bNAbs).

To achieve the goal of the longer-acting therapy, Joseph J. Eron, MD, of the University of North Carolina at Chapel Hill, and colleagues modified both antibodies to extend their half-lives and allow less-frequent dosing.

For the phase 1b trial, 20 adult patients with virologically suppressed HIV for at least 18 months were randomly assigned to one of two doses of the ART, both groups receiving lenacapavir at 927 mg subcutaneous after oral loading, plus teropavimab (30 mg/kg IV) and zinlirvimab at either 10 mg/kg or 30 mg/kg.

Patients had to have a CD4 count greater than 500 and CD4 nadir greater than 350, and importantly, patients had to demonstrate sensitivity on DNA phenotyping to both bNAbs at baseline.

After 26 weeks, 18 of the 20 participants (90%) maintained a viral suppression of HIV-1 RNA less than 50 copies/mL.

Of the remaining two patients, one in the 10–mg/kg zinlirvimab group had a confirmed HIV RNA of 50 c/mL (155 copies/mL, confirmed 524 copies/mL) at week 16 and was able to be resuppressed with reinitiation of baseline ART, and one participant in the zinlirvimab 30 mg/kg group withdrew consent at week 12, with viral suppression, and chose to go back on oral therapy

The safety profile looked favorable, with no serious adverse events and two patients with grade 3 AEs, including one experiencing an injection site cellulitis and one with injection site erythema.

Dr. Eron noted that “bNAb sensitivity is an important issue and a limitation for broad use, [because] only about 50% of people with HIV in the U.S. would be sensitive to both antibodies.”

However, “we are doing a pilot of only 10 participants looking to see if it works with sensitivity to a single antibody, which would increase [applicability] to about 90% of people with HIV,” he said in an interview.

At a press conference, Dr. Eron commented on how far HIV treatment has come, from the early days of patients having to wake up every 4 hours to take their medication, then to having to take 15-20 pills a day, to the current option of long-acting ART every other month, and now the potential of just a twice-yearly treatment.

“This is a very preliminary proof-of-concept study and not a very large study, but I think it’s incredibly important,” he said.

The SOLAR study was funded by ViiV Healthcare. Dr. Ramgopal has received speaking and/or consulting fees from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Eron’s study was funded by Gilead Sciences.

A version of this article first appeared on Medscape.com.

Long-acting antiretroviral therapy (ART) for HIV involving injections every 1 or 2 months not only shows noninferiority to a standard daily oral treatment regimen, it also suppresses HIV even in patients who do not already have virologic suppression, as is typically required before initiation, results from two new studies suggest.

Meanwhile, a third study shows early promise of a long-acting ART regimen that could require injections only twice yearly.

“Instead of having the burden of taking a pill every day, patients with HIV can now have these choices of being able to forget about their treatment for up to 2 months at a time,” Moti N. Ramgopal, MD, first author of one of the three studies, said in a press conference at the Conference on Retroviruses and Opportunistic Infections. “My patients tell me that it’s game-changing for them.”
 

First head-to-head comparison

The injectable intramuscular combination of cabotegravir and rilpivirine, administered once every 1 or 2 months, is the first and only long-acting ART to be approved by the Food and Drug Administration for people with HIV. At the meeting, Dr. Ramgopal, from the Midway Immunology and Research Center in Fort Pierce, Fla., reported the results from the first head-to-head study comparing the regimen with the standard daily oral regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).

For the phase 3b SOLAR trial, adults with HIV who were already virologically suppressed and treated with daily B/FTC/TAF were randomly assigned to remain on the oral regimen (n = 223) or switch to the long-acting injections every 2 months, either with an oral lead-in (n = 173) or without a lead-in (n = 274).

The results after 12 months showed noninferiority between the groups, with 90% of the long-acting ART group and 93% in the oral daily pill group maintaining viral suppression, defined as plasma HIV-1 RNA less than 50 copies/mL.

Two patients (0.4%) receiving the long-acting ART in a modified-intention to treat and 3 (0.6%) in the intention-to-treat populations had confirmed virologic failure, and rates of adverse events leading to withdrawal were 6% with the long-acting ART group versus 1% with the oral treatment group.

As many as 90% of subjects reported preferring the long-acting ART over their previous oral therapy at the end of the study, and those in the long-acting group also reported significantly greater improvements in quality of life on the HIV Treatment Satisfaction Questionnaire status version compared with the oral therapy group at the end of the study (P < .001).

Prior to the randomization, as many as 47% of patients on the oral regimen reported “always” or “often” having psychosocial challenges with the daily therapy, including worries of having their HIV status revealed and forgetting to take the medication.

“These data demonstrate that [the long-acting regimen] addresses important unmet needs for people with HIV who are virally suppressed on oral daily HIV therapy, while improving the quality of life,” said Dr. Ramgopal.
 

Suppression at onset not necessarily required

For all of its benefits, a key caveat of the cabotegravir and rilpivirine long-acting regimen is that it is approved only for patients who have already achieved viral suppression and are currently on oral ART, meaning some of the people most in need, including those with unstable housing, mental illness, or substance abuse disorders, may be excluded.

To evaluate the therapy’s efficacy among those patient types, Monica Gandhi, MD, MPH, professor of medicine and associate division chief at the University of California, San Francisco, enrolled 133 participants between June 2021 and November 2022 at the Ward 86 HIV Clinic, a safety-net clinic in San Francisco, to initiate long-acting ART. Participants included 57 patients (43%) with untreated or unsuppressed HIV, and 76 who were virally suppressed on oral ART.

Of the whole study group, 66% reported unstable housing, 8% reported experiencing homelessness, 38% reported having a mental illness, and 33% reported substance use.

Although all of the subjects (100%) who started with viral suppression remained suppressed over the study’s 26-week follow-up, the rate of viral suppression at the study’s end was nearly as high – 55 of 57 subjects (96.5%) – among those who started long-acting ART without having viral suppression.

Of note, the overall rate of study participants who did not achieve or maintain viral suppression (1.5%) was consistent with rates reported in clinical trials of long-acting ART in people with HIV who had previously achieved viral suppression on daily oral ART.

“Our patient population does not look like the patient population that got enrolled in the clinical trials to determine the approval criteria for long-acting ART,” Dr. Gandhi said in presenting the findings.

“If 10% of the population carries 90% of the HIV virus – which we see in modeling – then we need innovations for this population if we want to end the HIV epidemic,” she added.

“We tried long-acting ART in our diverse, urban, low-income population and we saw very high virologic suppression rates equal to those that were seen in the clinical trials,” Dr. Ghandi reported. “This shows that long-acting ART, used creatively and used boldly, could really make a dent in the [efforts] to end the HIV epidemic movement.”

Commenting on the study in a press statement, Nora Volkow, MD, director of the National Institute on Drug Abuse, said “Dr. Gandhi and her team have made state-of-the-art HIV treatment finally available to people with unique challenges, like those who use drugs, and have found success.”

“This is the sweet spot for addressing HIV – thinking outside the box to deliver care in a way that meets people’s needs, even when that means it happens outside the clinic walls, by phone, or on neighborhood streets,” she said. “This can be done, but it requires creativity and resolve.”
 

Twice-yearly dosing option?

Looking ahead, an even more intriguing scenario of a long-acting ART requiring injections only once every 6 months may be getting closer to fruition. Researchers at CROI 2023 reported early but promising safety and efficacy results of an innovative combination of the first-in-class HIV-1 capsid inhibitor lenacapavir with teropavimab and zinlirvimab, two broadly neutralizing antibodies (bNAbs).

To achieve the goal of the longer-acting therapy, Joseph J. Eron, MD, of the University of North Carolina at Chapel Hill, and colleagues modified both antibodies to extend their half-lives and allow less-frequent dosing.

For the phase 1b trial, 20 adult patients with virologically suppressed HIV for at least 18 months were randomly assigned to one of two doses of the ART, both groups receiving lenacapavir at 927 mg subcutaneous after oral loading, plus teropavimab (30 mg/kg IV) and zinlirvimab at either 10 mg/kg or 30 mg/kg.

Patients had to have a CD4 count greater than 500 and CD4 nadir greater than 350, and importantly, patients had to demonstrate sensitivity on DNA phenotyping to both bNAbs at baseline.

After 26 weeks, 18 of the 20 participants (90%) maintained a viral suppression of HIV-1 RNA less than 50 copies/mL.

Of the remaining two patients, one in the 10–mg/kg zinlirvimab group had a confirmed HIV RNA of 50 c/mL (155 copies/mL, confirmed 524 copies/mL) at week 16 and was able to be resuppressed with reinitiation of baseline ART, and one participant in the zinlirvimab 30 mg/kg group withdrew consent at week 12, with viral suppression, and chose to go back on oral therapy

The safety profile looked favorable, with no serious adverse events and two patients with grade 3 AEs, including one experiencing an injection site cellulitis and one with injection site erythema.

Dr. Eron noted that “bNAb sensitivity is an important issue and a limitation for broad use, [because] only about 50% of people with HIV in the U.S. would be sensitive to both antibodies.”

However, “we are doing a pilot of only 10 participants looking to see if it works with sensitivity to a single antibody, which would increase [applicability] to about 90% of people with HIV,” he said in an interview.

At a press conference, Dr. Eron commented on how far HIV treatment has come, from the early days of patients having to wake up every 4 hours to take their medication, then to having to take 15-20 pills a day, to the current option of long-acting ART every other month, and now the potential of just a twice-yearly treatment.

“This is a very preliminary proof-of-concept study and not a very large study, but I think it’s incredibly important,” he said.

The SOLAR study was funded by ViiV Healthcare. Dr. Ramgopal has received speaking and/or consulting fees from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Eron’s study was funded by Gilead Sciences.

A version of this article first appeared on Medscape.com.

Long-acting antiretroviral therapy (ART) for HIV involving injections every 1 or 2 months not only shows noninferiority to a standard daily oral treatment regimen, it also suppresses HIV even in patients who do not already have virologic suppression, as is typically required before initiation, results from two new studies suggest.

Meanwhile, a third study shows early promise of a long-acting ART regimen that could require injections only twice yearly.

“Instead of having the burden of taking a pill every day, patients with HIV can now have these choices of being able to forget about their treatment for up to 2 months at a time,” Moti N. Ramgopal, MD, first author of one of the three studies, said in a press conference at the Conference on Retroviruses and Opportunistic Infections. “My patients tell me that it’s game-changing for them.”
 

First head-to-head comparison

The injectable intramuscular combination of cabotegravir and rilpivirine, administered once every 1 or 2 months, is the first and only long-acting ART to be approved by the Food and Drug Administration for people with HIV. At the meeting, Dr. Ramgopal, from the Midway Immunology and Research Center in Fort Pierce, Fla., reported the results from the first head-to-head study comparing the regimen with the standard daily oral regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).

For the phase 3b SOLAR trial, adults with HIV who were already virologically suppressed and treated with daily B/FTC/TAF were randomly assigned to remain on the oral regimen (n = 223) or switch to the long-acting injections every 2 months, either with an oral lead-in (n = 173) or without a lead-in (n = 274).

The results after 12 months showed noninferiority between the groups, with 90% of the long-acting ART group and 93% in the oral daily pill group maintaining viral suppression, defined as plasma HIV-1 RNA less than 50 copies/mL.

Two patients (0.4%) receiving the long-acting ART in a modified-intention to treat and 3 (0.6%) in the intention-to-treat populations had confirmed virologic failure, and rates of adverse events leading to withdrawal were 6% with the long-acting ART group versus 1% with the oral treatment group.

As many as 90% of subjects reported preferring the long-acting ART over their previous oral therapy at the end of the study, and those in the long-acting group also reported significantly greater improvements in quality of life on the HIV Treatment Satisfaction Questionnaire status version compared with the oral therapy group at the end of the study (P < .001).

Prior to the randomization, as many as 47% of patients on the oral regimen reported “always” or “often” having psychosocial challenges with the daily therapy, including worries of having their HIV status revealed and forgetting to take the medication.

“These data demonstrate that [the long-acting regimen] addresses important unmet needs for people with HIV who are virally suppressed on oral daily HIV therapy, while improving the quality of life,” said Dr. Ramgopal.
 

Suppression at onset not necessarily required

For all of its benefits, a key caveat of the cabotegravir and rilpivirine long-acting regimen is that it is approved only for patients who have already achieved viral suppression and are currently on oral ART, meaning some of the people most in need, including those with unstable housing, mental illness, or substance abuse disorders, may be excluded.

To evaluate the therapy’s efficacy among those patient types, Monica Gandhi, MD, MPH, professor of medicine and associate division chief at the University of California, San Francisco, enrolled 133 participants between June 2021 and November 2022 at the Ward 86 HIV Clinic, a safety-net clinic in San Francisco, to initiate long-acting ART. Participants included 57 patients (43%) with untreated or unsuppressed HIV, and 76 who were virally suppressed on oral ART.

Of the whole study group, 66% reported unstable housing, 8% reported experiencing homelessness, 38% reported having a mental illness, and 33% reported substance use.

Although all of the subjects (100%) who started with viral suppression remained suppressed over the study’s 26-week follow-up, the rate of viral suppression at the study’s end was nearly as high – 55 of 57 subjects (96.5%) – among those who started long-acting ART without having viral suppression.

Of note, the overall rate of study participants who did not achieve or maintain viral suppression (1.5%) was consistent with rates reported in clinical trials of long-acting ART in people with HIV who had previously achieved viral suppression on daily oral ART.

“Our patient population does not look like the patient population that got enrolled in the clinical trials to determine the approval criteria for long-acting ART,” Dr. Gandhi said in presenting the findings.

“If 10% of the population carries 90% of the HIV virus – which we see in modeling – then we need innovations for this population if we want to end the HIV epidemic,” she added.

“We tried long-acting ART in our diverse, urban, low-income population and we saw very high virologic suppression rates equal to those that were seen in the clinical trials,” Dr. Ghandi reported. “This shows that long-acting ART, used creatively and used boldly, could really make a dent in the [efforts] to end the HIV epidemic movement.”

Commenting on the study in a press statement, Nora Volkow, MD, director of the National Institute on Drug Abuse, said “Dr. Gandhi and her team have made state-of-the-art HIV treatment finally available to people with unique challenges, like those who use drugs, and have found success.”

“This is the sweet spot for addressing HIV – thinking outside the box to deliver care in a way that meets people’s needs, even when that means it happens outside the clinic walls, by phone, or on neighborhood streets,” she said. “This can be done, but it requires creativity and resolve.”
 

Twice-yearly dosing option?

Looking ahead, an even more intriguing scenario of a long-acting ART requiring injections only once every 6 months may be getting closer to fruition. Researchers at CROI 2023 reported early but promising safety and efficacy results of an innovative combination of the first-in-class HIV-1 capsid inhibitor lenacapavir with teropavimab and zinlirvimab, two broadly neutralizing antibodies (bNAbs).

To achieve the goal of the longer-acting therapy, Joseph J. Eron, MD, of the University of North Carolina at Chapel Hill, and colleagues modified both antibodies to extend their half-lives and allow less-frequent dosing.

For the phase 1b trial, 20 adult patients with virologically suppressed HIV for at least 18 months were randomly assigned to one of two doses of the ART, both groups receiving lenacapavir at 927 mg subcutaneous after oral loading, plus teropavimab (30 mg/kg IV) and zinlirvimab at either 10 mg/kg or 30 mg/kg.

Patients had to have a CD4 count greater than 500 and CD4 nadir greater than 350, and importantly, patients had to demonstrate sensitivity on DNA phenotyping to both bNAbs at baseline.

After 26 weeks, 18 of the 20 participants (90%) maintained a viral suppression of HIV-1 RNA less than 50 copies/mL.

Of the remaining two patients, one in the 10–mg/kg zinlirvimab group had a confirmed HIV RNA of 50 c/mL (155 copies/mL, confirmed 524 copies/mL) at week 16 and was able to be resuppressed with reinitiation of baseline ART, and one participant in the zinlirvimab 30 mg/kg group withdrew consent at week 12, with viral suppression, and chose to go back on oral therapy

The safety profile looked favorable, with no serious adverse events and two patients with grade 3 AEs, including one experiencing an injection site cellulitis and one with injection site erythema.

Dr. Eron noted that “bNAb sensitivity is an important issue and a limitation for broad use, [because] only about 50% of people with HIV in the U.S. would be sensitive to both antibodies.”

However, “we are doing a pilot of only 10 participants looking to see if it works with sensitivity to a single antibody, which would increase [applicability] to about 90% of people with HIV,” he said in an interview.

At a press conference, Dr. Eron commented on how far HIV treatment has come, from the early days of patients having to wake up every 4 hours to take their medication, then to having to take 15-20 pills a day, to the current option of long-acting ART every other month, and now the potential of just a twice-yearly treatment.

“This is a very preliminary proof-of-concept study and not a very large study, but I think it’s incredibly important,” he said.

The SOLAR study was funded by ViiV Healthcare. Dr. Ramgopal has received speaking and/or consulting fees from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Eron’s study was funded by Gilead Sciences.

A version of this article first appeared on Medscape.com.