S148: Venetoclax-Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia: 5-Year Results of the Randomized Cll14 Study

Al-Sawaf, O.; Zhang, C.; Robrecht, Sandra; Kotak, Alex; Chang, N.; Fink, Anna‐Maria; Tausch, Eugen; Schneider, Carolin; Ritgen, Matthias; Kreuzer, Karl; Chyla, Brenda; Eichhorst, Barbara; Jiang, Y.; Stilgenbauer, S.; Hallek, Michael; Fischer, Kirsten

doi:10.1097/01.hs9.0000843484.72409.00

Cited by 11 publications

(21 citation statements)

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“…The venetoclax-obinutuzumab arm showed longer PFS at 24 months (88.2 vs. 64.1%) and complete remission rate (49.5 vs. 23.1%) [112 ▪ ]. After 4 years of follow-up, there have been no differences in OS [113]. The main reported toxicities associated with venetoclax are not only grade 3–4 neutropenia, which is the most common adverse event, but also grade 3–4 thrombocytopenia and anaemia can occur.…”

Section: Pathway Inhibitorsmentioning

confidence: 90%

“…Importantly, updates of the CLL14 trial and the Murano trial have reported that the presence of TP53 aberrations remain a poor response predictive factor for these regimens. In addition, in the front-line setting, patients with uIGHV had shorter duration of the response, the median PFS being 57.3 months vs. not reached in patients with mutated IGHV under venetoclax-obinutuzumab [113].…”

Section: Pathway Inhibitorsmentioning

confidence: 96%

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The road to chemotherapy-free treatment in chronic lymphocytic leukaemia

Albiol

Arguello-Tomas

Moreno

2021

Current Opinion in Oncology

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Purpose of reviewThe treatment landscape of chronic lymphocytic leukaemia (CLL) has tremendously evolved in the last decades, from chemo to chemoimmunotherapy (CIT) and, eventually, to pathway inhibitors that target critical pathways for leukaemic cells survival. Also, treatment goals are moving towards achieving undetectable minimal residual disease with little toxicity. Recent findingsWe performed a thorough review of the history of treatment approvals by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This review especially focuses on therapies that are currently approved by both agencies. The indications and particular characteristics of each drug are examined. SummaryCurrently available treatment approaches for CLL offer the opportunity to individualize therapy for every single patient with CLL. Inhibitors of B-cell receptor (BCR) signalling pathways and antiapoptotic proteins are nowadays the treatment of choice for most CLL patients, but CIT can be an option for younger and fit patients with low-risk disease [mutated IGHV, no del(11q) or del(17p)/TP53 mutations].

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Section: Pathway Inhibitorsmentioning

confidence: 90%

Section: Pathway Inhibitorsmentioning

confidence: 96%

The road to chemotherapy-free treatment in chronic lymphocytic leukaemia

Albiol

Arguello-Tomas

Moreno

2021

Current Opinion in Oncology

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“…Updated follow-up data were presented at the European Congress; and, at a median follow-up of 65.4 months, PFS was superior for venetoclaxobinutuzumab (not reached vs. 36.4 months; HR, 0.35). 19,20 The estimated 5-year PFS was 62.6% with this combination versus 27% in the chlorambucil arm. Notably, the PFS was substantially lower in patients with TP53 aberrations, who demonstrated a PFS of 52% at 4 years and 40.6% at 5 years.…”

Section: Frontline Venetoclax Therapymentioning

confidence: 99%

“…The estimated 5‐year PFS was 62.6% with this combination versus 27% in the chlorambucil arm. Notably, the PFS was substantially lower in patients with TP53 aberrations, who demonstrated a PFS of 52% at 4 years and 40.6% at 5 years 20,21 . As discussed below, this prompted cross‐trial comparisons with BTK inhibition, suggesting that—all other things being equal—fixed‐duration venetoclax‐obinutuzumab therapy may not be the ideal initial treatment regimen of choice in patients with this high‐risk aberration.…”

Section: Frontline Venetoclax Therapymentioning

confidence: 99%

Novel combination approaches with targeted agents in frontline chronic lymphocytic leukemia

Lipsky

Lamanna

2022

Cancer

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Targeted therapies have revolutionized the frontline treatment landscape for patients with chronic lymphocytic leukemia (CLL) and have largely displaced a reliance on chemoimmunotherapy when treating this disease. Multiple randomized trials have documented the efficacy of oral therapy with the Bruton tyrosine kinase inhibitors ibrutinib and acalabrutinib (and zanubrutinib, pending a supplemental new drug application in CLL), as well as BCL2 inhibition using venetoclax. In this review, the authors highlight novel therapeutic strategies for using these agents in combination, either as doublet therapy or as triplet therapy, with anti-CD20 antibodies.First, the current treatment landscape is outlined, and the data are reviewed for continuous and time-limited therapeutic approaches, which constitute the current standard of care. Then, more recent reports are described from phase 2 and 3 studies exploring different combination strategies of Bruton tyrosine kinase and BCL2 inhibition for treatment-naive patients. In addition, relevant differences are emphasized between patient characteristics (e.g., patient fitness and the presence of high-risk disease features) and study methodology (e.g., dosing schedule, randomization, and assessment of measurable residual disease) across trials. Finally, the authors revisit the currently available data for these approaches in the context of ongoing studies and future planned trials, evaluating their potential impact on the frontline treatment landscape for CLL in the years to come.

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“…2 At 5-year follow-up, VenO treated patients had improved PFS over ChlO; 62.6% vs. 27.0%. 7 In fit patients in GAIA/CLL13, VenO demonstrated superior PB uMRD rates (86.5% vs. 52.0%; p<0.0001) and PFS (HR 0.42 [97.5% CI 0.26-0.68); p<0.0001) compared with CIT (age-stratified fludarabine-cyclophosphamide-rituximab…”

mentioning

confidence: 98%