Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial

Tam, Constantine S.; Brown, Jennifer R.; Kahl, Brad S.; Ghia, Paolo; Giannopoulos, Krzysztof; Jurczak, Wojciech; Šimkovič, Martin; Shadman, Mazyar; Österborg, Anders; Laurenti, Luca; Walker, Patricia; Opat, Stephen; Chan, Henry; Ciepłuch, Hanna; Greil, Richard; Tani, Monica; Trněný, Marek; Brander, Danielle M.; Flinn, Ian W.; Grosicki, Sebastian; Verner, Emma; Tedeschi, Alessandra; Li, Jianyong; Tian, Tian; Zhou, Lei; Marimpietri, Carol; Paik, Jason C.; Cohen, Aileen; Huang, Jane; Robak, Tadeusz; Hillmen, Peter

doi:10.1016/s1470-2045(22)00293-5

Cited by 101 publications

(100 citation statements)

References 29 publications

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“…After a median follow-up of 47 months, the estimated PFS at 4 years was 87% with acalabrutinib-obinutuzumab vs. 78% with acalabrutinib monotherapy vs. 25% with chlorambucil-obinutuzumab ( P < 0.0001 for comparison of acalabrutinib containing regimens to chlorambucil-obinutuzumab) [ 36 ]. The SEQUOIA study compared zanubrutinib to BR in 590 previously untreated CLL patients (median age = 70 years, del17p patients excluded); after a median follow-up of 26 months, the estimated 24-month PFS was 85% with zanubrutinib compared to 69% with BR ( P < 0·0001) [ 37 ]. Zanubrutinib does not yet have approval for CLL in the United States but is listed as a “category 1” recommendation on the NCCN Guidelines (Version 1.2023).…”

Section: Management Of the Patient With Previously Untreated Cllmentioning

confidence: 99%

Chronic lymphocytic leukemia treatment algorithm 2022

Hampel

2022

Blood Cancer J.

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The treatment landscape for patients with chronic lymphocytic leukemia (CLL) has changed considerably with the introduction of very effective oral targeted therapies (such as Bruton tyrosine kinase inhibitors and venetoclax) and next-generation anti-CD20 monoclonal antibodies (such as obinutuzumab). These agents lead to improved outcomes in patients with CLL, even among those with high-risk features, such as del17p13 or TP53 mutation and unmutated immunoglobulin heavy chain (IGHV) genes. Selecting the right treatment for the right patient requires consideration of disease characteristics and prior treatment sequence, as well as patient preferences and comorbidities. The CLL-International Prognostic Index (CLL-IPI) remains the best-validated tool in predicting the time to first therapy among previously untreated patients, which guides selection for early intervention efforts. This review summarizes our current approach to the management of CLL, right from the time of diagnosis through relapsed disease.

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Section: Management Of the Patient With Previously Untreated Cllmentioning

confidence: 99%

Chronic lymphocytic leukemia treatment algorithm 2022

Hampel

2022

Blood Cancer J.

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“…The indications for zanubrutinib include MCL, WM, and MZL 434,435 . Though not approved for CLL/SLL, the recent results of the phase III SEQUOIA trial proved that zanubrutinib significantly improved PFS versus bendamustine–rituximab and is a potential new treatment option for untreated CLL/SLL 436 . Similar to the relationship between acalabrutinib and ibrutinib, zanubrutinib treatment was associated with a better response rate and less toxicity when compared with ibrutinib in treating patients with WM 437 …”

Section: Selective Small Molecule Kinase Inhibitorsmentioning

confidence: 98%

Small molecule inhibitors targeting the cancers

Liu

Chen

Zhang

et al. 2022

MedComm

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Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary targeted therapies for cancer. Due to their advantages in a wide range of targets, convenient medication, and the ability to penetrate into the central nervous system, many efforts have been devoted to developing more small molecule inhibitors. To date, 88 small molecule inhibitors have been approved by the United States Food and Drug Administration to treat cancers. Despite remarkable progress, small molecule inhibitors in cancer treatment still face many obstacles, such as low response rate, short duration of response, toxicity, biomarkers, and resistance. To better promote the development of small molecule inhibitors targeting cancers, we comprehensively reviewed small molecule inhibitors involved in all the approved agents and pivotal drug candidates in clinical trials arranged by the signaling pathways and the classification of small molecule inhibitors. We discussed lessons learned from the development of these agents, the proper strategies to overcome resistance arising from different mechanisms, and combination therapies concerned with small molecule inhibitors. Through our review, we hoped to provide insights and perspectives for the research and development of small molecule inhibitors in cancer treatment.

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“…Continuous treatment with ibrutinib has demonstrated its high efficacy regardless of high-risk biologic features and its superiority over chemoimmunotherapy in relapsed/refractory (R/R) CLL and previously untreated patients [4][5][6][7][8][9][10][11][12] . Recent studies have shown similar efficacy with a better toxicity profile of the covalent BTK inhibitors acalabrutinib [13][14][15] and zanubrutinib [16][17][18] . The effectiveness of the non-covalent BTK inhibitor, pirtobrutinib, in patients with resistance to ibrutinib due to BTK mutation has also been described 19 .…”

Section: Introductionmentioning

confidence: 99%

High rate of durable responses with undetectable minimal residual disease with front-line venetoclax and rituximab in young, fit patients with chronic lymphocytic leukemia and an adverse biological profile: results of the GIMEMA phase II LLC1518 – VERITAS study

et al. 2023

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The GIMEMA phase II LLC1518 VERITAS trial investigated the efficacy and safety of frontline, fixed-duration venetoclax and rituximab (VenR) combination in young (≤65 years) and fit patients with chronic lymphocytic leukemia (CLL) and unmutated IGHV and/or TP53 disruption. Treatment consisted of the Ven ramp-up, six-monthly courses of the VenR combination, followed by six monthly courses of Ven single agent. A centralized assessment of measurable minimal residual disease (MRD) was performed on the peripheral blood (PB) and bone marrow (BM) by ASO-PCR at the end of treatment (EOT) and during the follow-up. The primary endpoint was the complete remission (CR) rate at the EOT. Seventy-five patients were enrolled; the median age was 54 years (range 38-65), 96% had unmutated IGHV, 9 (12%) had TP53 disruption, and 4% were IGHV mutated with TP53 disruption. The overall response rate (ORR) at the EOT was 94.7%, with a CR rate of 76%. An undetectable (u) MRD was recorded in 69.3% of patients in the PB and 58.7% in the BM. The 12-month MRD-free survival in the 52 patients with uMRD in the PB at the EOT was 73.1%. After a median follow-up of 20.8 months, no disease progressions were observed. Three patients have died, two due to Covid-19 and 1 to tumor lysis syndrome. The first report of the VERITAS study shows that frontline VenR was associated with a high rate of CRs and durable responses with uMRD in young patients with CLL and unfavorable genetic characteristics.

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Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial

Cited by 101 publications

References 29 publications

Chronic lymphocytic leukemia treatment algorithm 2022

Chronic lymphocytic leukemia treatment algorithm 2022

Small molecule inhibitors targeting the cancers

High rate of durable responses with undetectable minimal residual disease with front-line venetoclax and rituximab in young, fit patients with chronic lymphocytic leukemia and an adverse biological profile: results of the GIMEMA phase II LLC1518 – VERITAS study

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