Updates in the Management of CLL/SLL: Management of Relapsed/Refractory Disease and the Role of Minimal Residual Disease

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Jennifer R. Brown
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In relapsed chronic lymphocytic leukemia (CLL), the choice of therapy depends on the risk profile, prior therapy, and patient comorbidities. The first novel agent for patients who had previously received chemoimmunotherapy is typically a BTK inhibitor or combination venetoclax + rituximab. For patients with problematic comorbidities, however, a PI3K inhibitor can be used, but generally this is reserved for later lines of therapy. For those who stop ibrutinib due to adverse events, there are broad options but data are still limited. For those whose disease progresses on a BTK inhibitor, the only prospective data are for use of venetoclax. For patients who have been treated with venetoclax + rituximab and experience relapse, retreatment is a possibility if they have had a durable remission. Finally, undetectable minimal residual disease is strongly predictive of durability of response for time-limited regimens but not for continuous BTK inhibition, and is generally not indicated for monitoring patients.

Disclosures: Dr. Brown has disclosed receiving consulting fees from AbbVie, Inc., Acerta Pharmaceuticals LP, AstraZeneca Pharmaceuticals LP, BeiGene, Catapult Therapeutics, Eli Lilly and Company, Genentech, Inc., Juno Therapeutics, Inc./Celgene Corporation, MEI Pharma Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., and Rigel Pharmaceuticals, Inc.; receiving grant/research support from Loxo Oncology, Inc., TG Therapeutics, and Verastem, Inc.; and receiving other financial benefit from MorphoSys AG.

Correspondence: Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02115. Email: jbrown2@partners.org
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  • 1.

    O’Brien S , Furman RR , Coutre S , et al.. Single-agent ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience. Blood 2018;131:19101919.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Munir T , Brown JR , O'Brien S , et al.. Final analysis from RESONATE: up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Am J Hematol 2019;94:13531363.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Ghia P , Pluta A , Wach M , et al.. ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol 2020;38:28492861.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Calquence met primary efficacy endpoint in head-to-head trial against ibrutinib in chronic lymphocytic leukaemia [press release]. Wilmington, DE: Business Wire; January 25, 2021.

    • PubMed
    • Export Citation
  • 5.

    Tam CS , Trotman J , Opat S , et al.. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood 2019;134:851859.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Kater AP , Wu JQ , Kipps T , et al.. Venetoclax plus rituximab in relapsed chronic lymphocytic leukemia: 4-year results and evaluation of impact of genomic complexity and gene mutations from the MURANO phase III study. J Clin Oncol 2020;38:40424054.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Hillmen P , Rawstron AC , Brock K , et al.. Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: the CLARITY study [published correction appears in J Clin Oncol 2020;38:1644]. J Clin Oncol 2019;37:27222729.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Brown JR , Byrd JC , Coutre SE , et al.. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia. Blood 2014;123:33903397.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Mato AR , Nabhan C , Thompson MC , et al.. Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis. Haematologica 2018;103:874879.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Mato AR , Hill BT , Lamanna N , et al.. Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic lymphocytic leukemia: results from a multicenter study of 683 patients. Ann Oncol 2017;28:10501056.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Jones JA , Mato AR , Wierda WG , et al.. Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol 2018;19:6575.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Harrup RA , Owen C , D’Rozario J , et al.. Efficacy of subsequent novel targeted therapies, including repeated venetoclax-rituximab (VenR) in patients (Pts) with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) previously treated with fixed-duration VenR in the Murano study. Blood 2020;136(Suppl 1):4445.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Mato AR , Pagel JM , Coombs CC , et al.. LOXO-305, a next generation, highly selective, non-covalent BTK inhibitor in previously treated CLL/SLL: results from the phase 1/2 BRUIN study [abstract]. Presented at the 62nd ASH Annual Meeting and Exposition; December 5–8, 2020. Abstract 542.

    • PubMed
    • Export Citation

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