https://orcid.org/0000-0003-1744-4145
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ABSTRACT
Introduction
Chronic lymphocytic leukemia (CLL) is a genetically complex disease that affects a heterogeneous patient population. Therapeutic armamentarium of CLL has changed recently following the introduction of novel active agents.
Areas covered
This review presents the current state of knowledge about biologic drugs used in the treatment of patients with CLL. It also discusses the biologics under evaluation in clinical trials and their potential future perspectives. A literature review of the MEDLINE database for articles was conducted via PubMed. Publications from 2000 through October 2019 were scrutinized using the search terms monoclonal antibodies, alloHSCT, vaccines and CAR-T in conjunction with CLL. Conference proceedings from the previous five years of the ASH and EHA Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles.
Expert opinion
When used in combination with chemotherapy and, more recently, with the Bcl-2 inhibitor venetoclax, anti-CD20 monoclonal antibodies (mAbs) are among the standard methods used for CLL treatment. Among the new mAbs, anti-ROR1 directed cirmtuzumab seems to have the most promising results. Adoptive immunotherapy with CAR-T is an area of intensive research, giving hope for achieving remission in patients with CLL refractory to all other methods of treatment.
Article highlights
Biologics are nowadays standard methods of CLL treatment, alongside chemotherapy, BCL-2 and BCR inhibitors.
Combination regimens comprising anti-CD20 monoclonal antibodies and chemotherapy are recommended as first line therapy in patients without 17p deletion/TP53 mutation, with mutated IGVH or with prolonged response after immunochemotherapy.
Although the role of immunochemotherapy is currently fading, anti-CD20 monoclonal antibodies can still play a strong role in CLL treatment by increasing the efficacy of venetoclax, a BCL-2 antagonist, allowing for time-limited treatment.
Among the new monoclonal antibodies, the anti-CD20 directed umbralisib and anti-ROR1 directed cirmtuzumab seem to have the most promising results.
Development of effective DC vaccines in CLL remains a challenge despite their proven ability to induce leukemia-specific T-cell responses. Improvement of clinical efficacy of this personalized treatment would require identification of more efficient combination strategies.
AlloHSCT remains the only therapeutic method with curative potential in CLL and should be considered in young and fit high-risk R/R CLL patients, refractory or relapsing after treatment with BCR inhibitors or BCL-2 antagonist.
CAR-T cell immunotherapy is the subject of intensive study in patients with CLL and will probably play an increasingly important role, especially in the light of encouraging preliminary results regarding combined CAR-T and ibrutinib therapy.
This box summarizes key points contained in the article.
Acknowledgments
We thank Edward Lowczowski from the Medical University of Lodz for editorial assistance.
Declaration of Interest
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was not utilized in the production of this manuscript.
Reviewer Disclosures
Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.