Small Lymphocytic Lymphoma

P1, N=19, Recruiting, University Health Network, Toronto | Trial completion date: May 2026 --> Jun 2028 | Trial primary completion date: Mar 2026 --> Jun 2028

P3, N=737, Recruiting, Loxo Oncology, Inc. | Trial primary completion date: Jun 2025 --> Oct 2027

This case highlights the diagnostic complexity of composite indolent B-cell lymphomas and underscores the importance of integrated clinical, morphologic, immunophenotypic, and molecular assessment to inform management and surveillance.

Phase 1 studies of docirbrutinib and rocbrutinib demonstrated target engagement across wild-type and resistance-associated BTK mutations with encouraging safety profiles and preliminary efficacy signals in heavily pretreated populations...BTK degraders, including bexobrutideg and BGB-16673, demonstrated rapid and deep responses, activity in high-risk molecular subgroups, and manageable toxicity profiles, with recommended phase 2 doses established. Collectively, these latest updates support continued clinical development of novel agents to address resistance and disease progression in R/R CLL/SLL.

P3, N=700, Recruiting, Janssen Research & Development, LLC | Trial completion date: Aug 2027 --> Dec 2029

Richter transformation of CLL represents an area of unmet need as most contemporary series report survival of less than 24 months. These guidelines summarize the Mayo Clinic approach to the diagnosis, risk stratification, and management of patients with CLL, including those with Richter transformation of CLL.

Classic Hodgkin lymphoma-type Richter transformation arises from convergent Hodgkin-like immune evasion on a genetically primed CLL/SLL background. Through integrated genomic and tumor microenvironment analyses in a large multicenter cohort, we establish this as a biologically coherent entity and provide rationale for PD-L1/PD-L2-directed therapeutic strategies.

P1/2, N=217, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2027 --> May 2028

Bruton tyrosine kinase inhibidors (BTKI), such as ibrutinib and zanubrutinib, represent a cornerstone of CLL/SLL treatment by inhibiting B-cell receptor signaling. The patient improved after BTKI reintroduction, and a P-RT was diagnosed. Nine similar patients were found through PubMed search, and we describe their clinicopathological characteristics.

P3, N=420, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting | Trial completion date: Aug 2033 --> Apr 2032 | Trial primary completion date: Nov 2032 --> Aug 2031

Case 1 was a 65-year-old woman diagnosed in 2017 with SMZL and treated with rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), and prednisone (or prednisolone) (R-CHOP), achieving complete remission, who presented nine years later with recurrent hyperlymphocytosis at 10.8 × 109/L with villous appearance, massive splenomegaly, and systemic symptoms...The patient was treated with rituximab-bendamustine and achieved complete remission...Rituximab monotherapy was followed by rapid improvement, with normalization of the lymphocyte count to 2.13 × 109/L and regression of splenomegaly from the first cycle. These observations highlight the importance of combining lymphocyte immunophenotyping and bone marrow aspiration in isolated splenomegaly with villous lymphocytes on blood smear to avoid underdiagnosis of this new histopathological entity and therefore guide therapeutic management in the absence of guidelines.

P2, N=20, Recruiting, National Cancer Institute (NCI) | Initiation date: Sep 2026 --> May 2026