Evidence map›Paper›PMID 39941798›Full record

ReviewCancers2025

Improving Treatment Options for Patients with Double Refractory CLL.

Ryan Jacobs, William Wierda

Abstract readReview
In one paragraph

Review in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Ryan JacobsAtrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC 28204, USA.ORCID 0000-0001-7814-7959
William WierdaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The proliferation and survival of chronic lymphocytic leukemia (CLL) cells are heavily dependent on B-cell receptor (BCR) signaling and resistance to apoptosis. Approvals of multiple covalent Bruton's tyrosine kinas inhibitors (cBTKis) as well as the B-cell lymphoma-2 inhibitor (BCL2i) venetoclax targeting these pathways have revolutionized the treatment of CLL and small lymphocytic lymphoma (SLL). The superiority of these treatments over chemoimmunotherapy has been proven in phase III studies in both treatment-naïve and relapsed refractory settings, leading to the majority of patients with CLL being treated sequentially with cBTKis and the BCL2i venetoclax as their first- and second-line therapies. While most patients with CLL respond for many years to these sequenced treatments, they are unfortunately not curative. There remains an unmet need for effective treatment options for patients who progressed after treatment with both cBTKis and BCL2i, also referred to as double refractory patients. Treatment options for double refractory CLL has improved recently with the approval of the non-covalent BTK inhibitor (ncBTKi) pirtobrutinib as well as the CD19 targeted chimeric antigen receptor T-cell (CAR T-cell) therapy lisocabtagene maraleucel (liso-cel). These recently approved treatment options for patients with CLL with at least two prior lines of therapy have fortunately demonstrated efficacy for double refractory CLL. Additionally, there are several novel treatment options in clinical development, including bi-specific antibodies, second-generation BCL2is, new ncBTKis, and BTK degraders. Understanding resistance mechanisms to existing cBTKis and venetoclax can potentially inform us of the best utilization of available treatment options for double refractory CLL and provide a personalized approach for these patients. In this review, a challenging example of a double refractory patient with CLL will serve as the basis for a review of available literature on the treatment of double refractory CLL/SLL.

Indexed as

B-cell lymphoma-2 inhibitorBruton’s tyrosine kinasechimeric antigen receptor T-cell therapychronic lymphocytic leukemiadouble refractorysmall lymphocytic lymphoma

Identifiers

PMID39941798
PMCPMC11816331

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.