CLL

CLL

11 records

• Level 2CLLpositive2018

  Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia (MURANO)

  Seymour JF, Kipps TJ, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, et al.. N Engl J Med. PMID 29562156. MRD as a key secondary/exploratory depth-of-response measure

  Phase 3 randomized venetoclax-rituximab vs bendamustine-rituximab in relapsed/refractory CLL, establishing fixed-duration Ven-R and high rates of undetectable MRD that were further analyzed in Kater et al., J Clin Oncol 2019 (PMID 30523712). Level 2.

• Level 2CLLpositive2019

  Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-up of the MURANO Phase III Study

  Kater AP, Seymour JF, Hillmen P, Eichhorst B, Langerak AW, Owen C, et al.. J Clin Oncol. PMID 30523712. Undetectable MRD after fixed-duration Ven-R

  Post-treatment MRD analysis of MURANO: fixed-duration venetoclax-rituximab produced high rates of undetectable MRD that were associated with longer survival. Level 2 (MRD analysis of an RCT).

• Level 2CLLpositive2019

  Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions (CLL14)

  Fischer K, Al-Sawaf O, Bahlo J, Fink AM, Tandon M, Dixon M, et al.. N Engl J Med. PMID 31166681. Undetectable MRD as a key depth-of-response endpoint (fixed-duration Ven-O vs Clb-O)

  Phase 3 first-line venetoclax-obinutuzumab vs chlorambucil-obinutuzumab in patients with CLL and coexisting conditions. Fixed-duration Ven-O produced high MRD-undetectable rates and a PFS benefit, with subsequent MRD-dynamics papers (Al-Sawaf JCO 2021; 6-year Blood 2024). Level 2.

• Level 2CLLpositive2021

  Minimal Residual Disease Dynamics after Venetoclax-Obinutuzumab Treatment: Extended Off-Treatment Follow-up From the Randomized CLL14 Study

  Al-Sawaf O, Zhang C, Lu T, Liao MZ, et al.. J Clin Oncol. PMID 34709929. Peripheral-blood MRD after end of fixed-duration Ven-O

  Extended off-treatment follow-up of CLL14 reporting MRD dynamics after venetoclax-obinutuzumab, including durability of undetectable MRD and its association with outcomes. Level 2.

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• Level 2CLLpositive2024

  Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study

  Al-Sawaf O, Robrecht S, Zhang C, Olivieri S, et al.. Blood. PMID 39082668. Long-term MRD and survival after fixed-duration Ven-O

  Six-year update of CLL14, including long-term PFS/OS and MRD outcomes after fixed-duration first-line venetoclax-obinutuzumab. Level 2.

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• Level 1CLLpositive2021

  Ibrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia: Primary Analysis Results From the Minimal Residual Disease Cohort of the Randomized Phase II CAPTIVATE Study

  Wierda WG, Allan JN, Siddiqi T, Kipps TJ, et al.. J Clin Oncol. PMID 34618601. Confirmed undetectable MRD used to randomize subsequent therapy (placebo vs ibrutinib) · n=Confirmed uMRD: 43 placebo, 43 ibrutinib

  Previously untreated CLL, age <70: 3 cycles ibrutinib then 12 cycles ibrutinib-venetoclax. Best uMRD 75% (PB) and 68% (BM). Patients with confirmed uMRD were randomized 1:1 to placebo or ibrutinib. 1-year DFS was 95% with placebo vs 100% with ibrutinib (difference 4.7%, 95% CI -1.6 to 10.9; P=0.15). Supports the potential for fixed-duration therapy after confirmed uMRD. Level 1 (MRD-guided randomized cohort).

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• Level 2CLLpositive2022

  Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort

  Tam CS, Allan JN, Siddiqi T, Kipps TJ, et al.. Blood. PMID 35196370. uMRD in PB and BM after fixed-duration I+V (not MRD-guided in this cohort)

  Fixed-duration (not MRD-guided) ibrutinib-venetoclax cohort. In the all-treated population, CR 55% (95% CI 48-63); best uMRD 77% (PB) and 60% (BM); 24-month PFS 95% and OS 98%. Level 2.

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• Level 1CLLpositive2024

  Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease (FLAIR)

  Munir T, Cairns DA, Bloor A, Allsup D, et al.. N Engl J Med. PMID 38078508. MRD-directed duration of ibrutinib-venetoclax (PB and BM MRD) · n=523

  Phase 3, previously untreated CLL: MRD-guided ibrutinib-venetoclax vs FCR (n=523). After 2 months of ibrutinib, venetoclax was added for up to 6 years, with duration guided by MRD. At median 43.7 months, progression or death occurred in 12 vs 75 patients (HR 0.13, 95% CI 0.07-0.24, P<0.001); death in 9 vs 25 (HR 0.31, 95% CI 0.15-0.67). At 3 years, 58.0% in the I+V group had stopped therapy because of undetectable MRD. After 5 years of I+V, 65.9% had undetectable MRD in BM and 92.7% in PB. Level 1 (randomized MRD-guided duration).

• Level 1CLLpositive2025

  Measurable Residual Disease-Guided Therapy for Chronic Lymphocytic Leukemia (FLAIR, extended follow-up)

  Munir T, Girvan S, Cairns DA, Bloor A, et al.. N Engl J Med. PMID 40521799. Undetectable BM MRD within 2 years; MRD-guided I+V vs ibrutinib vs FCR · n=260 I+V, 263 ibrutinib, 263 FCR

  Extended follow-up (median 62.2 months) and increased enrollment. Undetectable BM MRD within 2 years: 172/260 (66.2%) with I+V vs 0/263 with ibrutinib alone (P<0.001) vs 127/263 (48.3%) with FCR. Progression or death: 18 (6.9%) I+V vs 59 (22.4%) ibrutinib (HR 0.29, 95% CI 0.17-0.49, P<0.001) vs 112 (42.6%) FCR (HR 0.13, 95% CI 0.08-0.21, P<0.001). 5-year PFS 93.9% vs 79.0% vs 58.1%. OS also favored I+V (HR 0.41 vs ibrutinib; HR 0.26 vs FCR). Level 1.

• Level 2CLLpositive2023

  Impact of Minimal Residual Disease on Progression-Free Survival Outcomes After Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study

  Munir T, Moreno C, Owen C, Follows G, Benjamini O, Janssens A, et al.. J Clin Oncol. PMID 37279408. MRD after fixed-duration I+V (not MRD-guided)

  MRD analysis of the randomized GLOW trial of fixed-duration ibrutinib-venetoclax vs chlorambucil-obinutuzumab in older or comorbid first-line CLL, relating MRD status to PFS. Level 2 (MRD analysis of an RCT; therapy was fixed-duration, not MRD-guided).

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• Level 2CLLpositive2023

  First-Line Venetoclax Combinations in Chronic Lymphocytic Leukemia (GAIA/CLL13)

  Eichhorst B, Niemann CU, Kater AP, Fürstenau M, von Tresckow J, Zhang C, et al.. N Engl J Med. PMID 37163621. Undetectable MRD in PB by flow at month 15, sensitivity <10^-4 (co-primary with PFS) · n=926

  Phase 3, 926 fit CLL patients without TP53 aberrations, randomized 1:1:1:1 to CIT (FCR or BR), Ven-R, Ven-O, or Ven-O-ibrutinib (12 cycles of venetoclax combinations). At month 15, undetectable MRD was 86.5% with Ven-O and 92.2% with Ven-O-I vs 52.0% with CIT (P<0.001 for both), and 57.0% with Ven-R (P=0.32 vs CIT). 3-year PFS 90.5% Ven-O-I vs 75.5% CIT (HR 0.32, 97.5% CI 0.19-0.54, P<0.001); 87.7% Ven-O (HR 0.42, P<0.001); 80.8% Ven-R (HR 0.79, P=0.18). Level 2 (MRD was a co-primary endpoint of a randomized trial, but treatment was not MRD-guided).