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. 2020 Apr;27(2):e231-e245.
doi: 10.3747/co.27.6291. Epub 2020 May 1.

Updates from the American Society of Hematology 2019 annual meeting: practice-changing studies in treatment-naïve chronic lymphocytic leukemia

V Banerji  1 , P Anglin  2 , A Christofides  3 , S Doucette  3 , P Laneuville  4
Affiliations

Updates from the American Society of Hematology 2019 annual meeting: practice-changing studies in treatment-naïve chronic lymphocytic leukemia

V Banerji et al. Curr Oncol. 2020 Apr.

Abstract

The 2019 annual meeting of the American Society of Hematology took place 7-10 December in Orlando, Florida. At the meeting, results from key studies in treatment-naïve chronic lymphocytic leukemia (cll) were presented. Of those studies, phase iii oral presentations focused on the efficacy and safety of therapy with inhibitors of Bruton tyrosine kinase (btk) and Bcl-2. One presentation reported updated results of the Eastern Cooperative Oncology Group 1912 trial comparing the efficacy and safety of ibrutinib-rituximab with that of fludarabine-cyclophosphamide-rituximab in patients less than 70 years of age with cll. A second presentation reported interim results of the elevate tn trial, which is investigating the efficacy and safety of acalabrutinib-obinutuzumab or acalabrutinib monotherapy compared with chlorambucil-obinutuzumab. A third presentation reported on the single-agent zanubrutinib arm of the sequoia trial in patients with del(17p). The final presentation constituted a data update from the cll14 trial, which is evaluating fixed-duration venetoclax-obinutuzumab compared with chlorambucil-obinutuzumab, including the association of minimal residual disease status with progression-free survival. Our meeting report describes the foregoing studies and presents interviews with investigators and commentaries by Canadian hematologists about potential effects on Canadian practice.

Keywords: Chronic lymphocytic leukemia; treatment-naïve disease; untreated disease.

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Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare the following interests: VB has participated on advisory boards or has received research funding from AstraZeneca, AbbVie, Janssen, Roche, Gilead, and Teva Pharmaceuticals. She has received research funding from the Canadian Institutes of Health Research, the Leukemia and Lymphoma Society of Canada, the CancerCare Manitoba Foundation, and Research Manitoba. AC and SD received funding from AstraZeneca for the development of this document. PA has participated in advisory boards or has received honoraria from Janssen, AbbVie, Teva Pharmaceuticals, AstraZeneca, Apotex, and Celgene. PL has participated in advisory boards or has received honoraria from AbbVie, Amgen, ariad Pharmaceuticals, Ascentage Pharma, Bristol–Myers Squibb, Celgene, Gilead, Janssen, Lundbeck, Novartis, Paladin, Pfizer, and Roche.

Figures

FIGURE 1
FIGURE 1
E1912 study design. CLL = chronic lymphocytic leukemia; IWCLL = International Workshop on Chronic Lymphocytic Leukemia; ECOG = Eastern Cooperative Oncology Group; CrCl = creatinine clearance; FCR = fludarabine–cyclophosphamide–rituximab; FISH = fluorescence in situ hybridization; PO = orally; IV = intravenously.
FIGURE 2
FIGURE 2
Progression-free survival by IGHV mutation status. IGHV = immunoglobulin heavy chain variable region; HR = hazard ratio; CI = confidence interval; FCR = fludarabine–cyclophosphamide–rituximab; IR = ibrutinib–rituximab.
FIGURE 3
FIGURE 3
Overall survival in the the E1912 trial. HR = hazard ratio; CI = confidence interval; FCR = fludarabine–cyclophosphamide–rituximab; IR = ibrutinib–rituximab.
FIGURE 4
FIGURE 4
Design of the ELEVATE TN study. CLL = chronic lymphocytic leukemia; CIRS = Cumulative Illness Rating Scale; ECOG PS = Eastern Cooperative Oncology Group performance status; PO = orally; BID = twice daily; IV = intravenously; G-Clb = obinutuzumab–chlorambucil; IRC = independent review committee; PFS = progression-free survival; Acala-G = acalabrutinib–obinutuzumab; ORR = objective response rate; OS = overall survival.
FIGURE 5
FIGURE 5
Independent review committee–assessed progression-free survival (PFS) in the ELEVATE TN study. Acala-G = acalabrutinib–obinutuzumab; G-Clb = obinutuzumab–chlorambucil; CI = confidence interval.
FIGURE 6
FIGURE 6
Independent review committee–assessed progression-free survival by subgroup in the ELEVATE TN study. Acala-G = acalabrutinib–obinutuzumab; G-Clb = obinutuzumab–chlorambucil; CI = confidence interval; NE = not evaluable.
FIGURE 7
FIGURE 7
Design of the SEQUOIA trial. CLL = chronic lymphocytic leukemia; SLL = small lymphocytic lymphoma; iwCLL = International Workshop on Chronic Lymphocytic Leukemia; FCR = fludarabine–cyclophosphamide–rituximab; bid = twice daily; PD = progressive disease; FISH = fluorescence in situ hybridization.
FIGURE 8
FIGURE 8
Investigator-assessed progression-free survival in the SEQUOIA trial.
FIGURE 9
FIGURE 9
Adverse events of interest in the SEQUOIA trial.
FIGURE 10
FIGURE 10
Design of the CLL14 study. CLL = chronic lymphocytic leukemia; CIRS = Cumulative Illness Rating Scale.
FIGURE 11
FIGURE 11
Progression-free survival in the CLL14 study by IGHV mutation status.
FIGURE 12
FIGURE 12
Minimal residual disease (MRD) rates over time in the CLL14 study. μMRD = undetectable minimal residual disease; PD = progressive disease.
FIGURE 13
FIGURE 13
Progression-free survival (PFS) in the CLL14 study by minimal residual disease (MRD) status. EOT = end of treatment; μMRD = undetectable minimal residual disease.
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