Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Methods: Elderly or comorbid pts with untreated CLL/small lymphocytic leukemia were randomized 1:1 to Ibr+Ven (3 cycles Ibr lead-in then 12 cycles Ibr+Ven, n = 106) or 6 cycles Clb+O (n = 105). MRD in peripheral blood was measured by next-generation sequencing 3 months post-EOT (EOT+3), with undetectable MRD (uMRD) defined as < 10-4. TEAEs were collected until 30 days after EOT; therefore, AE collection was longer for Ibr+Ven vs Clb+O (median exposure: Ibr+Ven, 13.8 mo vs Clb+O, 5.1 mo). AEs after this were not considered tx emergent unless specifically considered tx related by investigator. Outcomes reported include investigator-assessed PFS, TTNT, and OS. Additionally, TEAE-free PFS was assessed (using restricted mean survival time, based on G3/4 TEAEs only), including quantification of time spent in different health states (time with G3/4 TEAEs and G3/4 TEAE-free PFS).
Results: At a median FU of 64 mo, Ibr+Ven prolonged PFS, reducing the risk of progression or death by 73% vs Clb+O (HR 0.27 [95% CI, 0.18-0.39]; p < 0.0001); 60-mo PFS rates were 59.9% and 17.8% for Ibr+Ven and Clb+O, respectively. Ibr+Ven prolonged PFS independent of IGHV status (unmutated IGHV [uIGHV], HR 0.26 [95% CI, 0.17-0.42]; p < 0.0001; mutated IGHV [mIGHV], HR 0.24 [95% CI, 0.10-0.62]; p = 0.0014). Estimated 60-mo PFS rates in the Ibr+Ven arm were 52.2% and 82.5% for pts with uIGHV (n = 67) and mIGHV (n = 32), respectively. In the Ibr+Ven arm, PFS rates at 48 mo post tx were 69% in pts who achieved uMRD at EOT+3 (n = 58) and 61% in pts with detectable MRD (dMRD; n = 31). Among Ibr+Ven-treated pts with uIGHV, PFS rates at 48 mo post tx were 67% for those achieving uMRD at EOT+3 (n = 40) and 40% for those with dMRD (n = 16). For Ibr+Ven-treated pts with mIGHV, PFS rates at 48 mo post-tx were ≥ 84% regardless of MRD status (uMRD, n = 13; dMRD, n = 14).
Ibr+Ven prolonged TTNT and reduced risk of need for second-line (2L) therapy vs Clb+O in pts with uIGHV (HR 0.18 [95% CI, 0.09-0.36]; p < 0.0001); there was no difference in TTNT in pts with mIGHV (HR 1.20 [95% CI, 0.31-4.60], p = 0.7878). Ibr+Ven prolonged OS vs Clb+O, reducing relative risk of death by 54% (HR 0.46 [95% CI, 0.27-0.79]; p = 0.004); 60-mo OS rates were 81.6% and 60.8% for Ibr+Ven and Clb+O, respectively. OS rates were prolonged in pts with mIGHV (HR 0.22 [95% CI, 0.06-0.77]; p = 0.010), while a trend was seen in pts with uIGHV (HR 0.51 [95% CI, 0.26-1.02]; p = 0.052).
At 64-mo FU, the time pts spent without significant toxicity or progression (TEAE-free PFS) was significantly longer for Ibr+Ven vs Clb+O (52 vs 31 mo, respectively). TEAE-free PFS analysis showed that while pts receiving 15 mo of Ibr+Ven spent slightly more time in the G3/4 toxicity state vs pts receiving 6 mo of Clb+O (2 vs 1 mo), pts in the Ibr+Ven arm spent substantially more time in TEAE-free PFS (50 vs 30 mo). These results show a 20-mo improvement in TEAE-free PFS with Ibr+Ven vs Clb+Ob, indicating longer disease control without significant toxicity.
Conclusion: With 64-mo FU, Ibr+Ven continues to show superior PFS, reduced risk of requiring 2L tx, and sustained OS advantage vs Clb+O. Moreover, analysis integrating clinical benefits and risks shows improved survival time free from G3/4 toxicity or relapse for Ibr+Ven. This long-term FU of time-limited Ibr+Ven provides valuable insights into the combination’s durable efficacy and tolerability profile, offering a robust foundation for informed clinical decision-making in pts with previously untreated CLL.
Disclosures: Niemann: AbbVie, Janssen, AstraZeneca, Novo Nordisk Foundation, Octapharma: Consultancy, Research Funding; Novo Nordisk: Research Funding; CSL Behring, Genmab, Takeda, Beigene, MSD, Lilly: Consultancy. Munir: Janssen, AbbVie, AstraZeneca, Alexion, Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees. Owen: AbbVie, AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Speaker; Janssen, Roche, Merck, Gilead, Servier, Seattle Genetics, Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Follows: Roche, AbbVie, Janssen, Takeda, Eli-Lilly, AstraZeneca: Consultancy, Other: Lecturing. Hernandez Rivas: BMS-Celgene: Research Funding; Janssen, Roche, Abbvie, AstraZeneca, Beigene, Lilly, Gilead, BMS-Celgene, Amgen, Takeda, Jazz Pharmaceuticals, Rovi, Incyte, MSD: Membership on an entity's Board of Directors or advisory committees; Janssen, Roche, Abbvie, AstraZeneca, Gilead, BMS-Celgene, Amgen, Takeda, Astra Zeneca, Lilly, Beigene: Other: Scientific Talks. Janssens: AbbVie, AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Speaker; AbbVie, AstraZeneca: Other: Travel; MSD: Consultancy; Amgen, Beigene, Janssen, Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Speaker; Eli lilly, Sobi: Other: Speaker; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Speaker; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees. Levin: Janssen, AbbVie: Other: Travel. Robak: Lilly: Research Funding; Cilag: Consultancy, Research Funding; GSK: Honoraria; Regeneron: Honoraria; OctoPharma: Honoraria; AstraZeneca: Consultancy, Honoraria, Other: Travel funding, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Takeda: Research Funding; Johnson & Johnson: Consultancy, Other: Travel funding. Simkovic: Janssen-Cilag, AstraZeneca, AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel. Voloshin: Abbvie: Honoraria, Other: non-financial clinical trial support; Janssen: Honoraria, Other: non-financial clinical trial support; Novartis: Honoraria, Other: non-financial clinical trial support; Astra Zeneca: Honoraria; Sanofi: Honoraria; BieGene: Other: non-financial clinical trial support; BIOCAD: Other: non-financial clinical trial support. Ysebaert: AbbVie, AstraZeneca, Janssen, Roche, Beigene, BMS/Celgene, Gilead/Kite: Membership on an entity's Board of Directors or advisory committees, Research Funding. Schuier: Janssen: Current Employment. Baeten: Janssen: Current Employment. Xu: Janssen: Current Employment. Tran: Janssen, Amgen: Current equity holder in publicly-traded company; Janssen: Current Employment. Levitan: Janssen: Current Employment, Current equity holder in publicly-traded company. Kavanagh: Janssen: Current Employment. Kater: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Patents planned, issued or pending; Steering Committee, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee, Research Funding; LAVA: Membership on an entity's Board of Directors or advisory committees, Other: Patents planned, issued or pending; Steering Committee; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding.
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