Lymphoplasmacytic Lymphoma

Aberrant B cell receptor signaling occurs in several B cell neoplasms including follicular lymphoma (treated with zanubrutinib, a BTK inhibitor), mantle cell lymphoma (acalabrutinib, pirtobrutinib, zanubrutinib), marginal zone lymphoma (zanubrutinib), chronic lymphocytic leukemia and small lymphocytic lymphoma (ibrutinib, acalabrutinib, zanubrutinib, pirtobrutinib), and Waldenström macroglobulinemia (ibrutinib, zanubrutinib)...Pirtobrutinib fails to form a covalent bond and is a reversible BTK inhibitor. The FDA-approvals of rilzabrutinib and remibrutinib (2025) represent the first nononcologic authorizations for BTK antagonists.

Furthermore, this review positions mavorixafor within the broader CXCR4-targeted therapeutic landscape, identifying current research gaps and suggesting directions for future studies. In conclusion, by integrating mechanistic insights with preclinical and clinical findings, this article highlights mavorixafor's promise as a targeted therapy with the potential to transform treatment paradigms for CXCR4-driven diseases.

Detection methodologies include allele-specific PCR for targeted L265P detection and next-generation sequencing for comprehensive mutational profiling. This review summarises the molecular biology, disease associations, clinical utility and therapeutic implications of MYD88 mutations in lymphoid malignancies.

At the molecular level, MYD88 mutation was significantly associated with favorable outcomes exclusively in patients treated with first-line BTKi-based therapy, while CXCR4 and TP53 mutations predicted significantly inferior prognosis in both BTKi-based and non-BTKi cohorts. Our findings indicate that although clinical risk models remain relevant for patients receiving non-BTKi therapy, molecular features, especially MYD88, CXCR4, and TP53 mutations, provide superior prognostic insights for patients with BTKi-based regimens.

Ibrutinib plus rituximab therapy was administered, resulting in a partial response sustained to date. Bone involvement and amyloidosis are rare but critical extranodal manifestations of LPL, necessitating careful screening and follow-up even in asymptomatic patients. When these manifestations are suspected, prompt pathological and genetic evaluation is warranted, especially in non-IgM LPL cases.

P=N/A, N=656, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jan 2026 --> Jan 2028 | Trial primary completion date: Jan 2026 --> Jan 2027

P1/2, N=50, Recruiting, Azienda Ospedaliera di Padova | Not yet recruiting --> Recruiting

P1, N=248, Recruiting, Nurix Therapeutics, Inc. | Trial completion date: Dec 2026 --> May 2027 | Trial primary completion date: Dec 2025 --> May 2026

Additionally, age > 65 years, bone marrow (BM) biopsy infiltration, haemoglobin 0.162 (either by ddPCR or quantitative PCR) together with multiparameter flow cytometry (MFC) infiltration >4.39% had a significant impact on OS and TTFT; the combination of MYD88 and MFC levels allowed to stratify patients into high-, intermediate-, and low-risk groups, with high-risk IgM gammopathy patients showing increased disease-related death in competing risk analysis.

P2, N=120, Active, not recruiting, Cellectar Biosciences, Inc. | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Jun 2026

Given the deep and durable responses seen in this study, concurrent BTK and BCL-2 inhibition warrants further development in WM. TP53 mutations emerged as an adverse factor in WM in this combination study.

P2, N=20, Recruiting, Gottfried von Keudell, MD PhD | Trial primary completion date: Oct 2025 --> Apr 2027