Chronic Lymphocytic Leukemia

P2, N=60, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

P1/2, N=20, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

Here, we provide an integrated, disease-spanning synthesis of these data, emphasizing clonal hematopoiesis and myeloid neoplasms as emerging examples of microbiota-marrow crosstalk and outlining practical priorities for embedding microbiome science into future hematologic trials. Routine microbiome profiling or empiric microbiota-directed therapies cannot yet be recommended in everyday hematology practice, but integrating microbiome science into prospective therapeutic and transplant trials offers a realistic path to improved disease modeling, biomarker development, and rational adjunctive strategies to enhance outcomes for patients with hematologic malignancies.

Knowledge of these alterations, both in the molecular pathways that modulate T cell activity in CLL (the T lymphocyte cytotoxic antigen-4 (CTLA-4) axis and programmed cell death 1 (PD-1)) and at the T cell immunoreceptor level, could be of interest as therapeutic targets in CLL. In this review, we will analyze the main consequences of this dysfunction and its management strategies.

To date, neither randomized nor retrospective trials have directly compared these approaches in RR CLL, and only limited data are available comparing venetoclax plus obinutuzumab (VenObi) to BTKi in the first-line setting. We retrospectively analysed 352 patients receiving second-line therapy: 93 VenR and 259 BTKi (ibrutinib: n = 222; acalabrutinib: n = 37)...Treatment discontinuation due to adverse events before month 24 was more frequent with BTKi (22.5% with VenR vs. 34.3% with BTKi), primarily due to infections (10.6% vs. 28.6%) and disease progression (14.3% vs. 22.5%). These preliminary data suggest comparable outcomes and manageable toxicity profiles for both regimens.

P2, N=20, Completed, University of Washington | Active, not recruiting --> Completed | Trial completion date: Aug 2029 --> Jan 2026

P3, N=49, Recruiting, Grifols Biologicals, LLC

P2, N=35, Not yet recruiting, City of Hope Medical Center

Despite the absence of peripheral lymphocytosis or established treatment indications for chronic lymphocytic leukemia (CLL), B-cell-directed therapy, including ibrutinib and venetoclax plus rituximab, was administered over the course of approximately one year based on the initial diagnostic impression, but failed to control hemolysis. Subsequent treatment with the C1s inhibitor sutimlimab resulted in sustained resolution of hemolysis. This case highlights diagnostic pitfalls in CAD and underscores the value of molecular profiling in guiding appropriate therapy.

P2, N=36, Recruiting, City of Hope Medical Center | Trial completion date: Apr 2026 --> Mar 2027 | Trial primary completion date: Apr 2026 --> Mar 2027

The findings support continued, tailored vaccination strategies for elderly and immunocompromised individuals. Integrating immune monitoring with infection history and adjunctive therapies may help refine booster policies, optimise protection, and strengthen future vaccination programmes for high-risk populations.

P2, N=26, Active, not recruiting, City of Hope Medical Center | Trial completion date: Apr 2026 --> Sep 2026 | Trial primary completion date: Apr 2026 --> Sep 2026