MYD88 mutation + CXCR4 mutation

Partial positivity for CD23 is a common feature of LPL in the BM. Together with other clinical and histological parameters, CD23 expression supports the differential diagnosis between LPL and MZL.

Testing for MYD88 mutations using AS-PCR or ddPCR in unsorted samples is viable for routine clinical practice. Under BTKi treatment, MYD88 and CXCR4 mutations hold greater prognostic importance than IPSSWM staging in WM.

Indolent T-cell lymphomas/lymphoproliferations of the GI tract are rare but must be differentiated from aggressive T-cell lymphomas. The WHO-HAEM5 also includes reactive/non-neoplastic lymph node lesions classified according to B or T cell predominance.

P1, N=13, Terminated, Dana-Farber Cancer Institute | Phase classification: P1/2 --> P1 | Active, not recruiting --> Terminated; Sponsor decision to end follow-up early

Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-naïve and relapsed/refractory patients (94% for all patients, 95% for treatment-naïve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% )...It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors' and patients' understanding of WM is one of the most urgent issues that must be addressed right now.

The cBTK-i zanubrutinib shows greater response activity and/or improved PFS in wild-type MYD88, mutated CXCR4, or altered TP53 patients...For patients with acquired resistance to c-BTKi, newer options include the non-covalent BTK-inhibitor pirtobrutinib or the BCL2 antagonist venetoclax. Combinations of BTK-inhibitors with chemoimmunotherapy, CXCR4 and BCL2 antagonists have advanced and are discussed. Algorithms for positioning BTK-inhibitors in treatment-naïve and previously treated WM patients based on genomics, disease characteristics, and co-morbidities are presented.

NGS was the most sensitive method for detecting CXCR4 mutation. MYD88 mutation had prognostic significance in BTKi-based therapy, while CXCR4 mutation indicated higher tumor burden and inferior survival in BTKi-based therapy.

MYD88 mutation and underlying haemopathies are not predictive of a more severe disease. However, in cases of resistant and progressive neuropathy, they provide an opportunity to prescribe newly available drugs such as Bruton tyrosine kinase inhibitors.

In addition to tumor genotype and patient comorbidities, choice of therapy in WM should take into account these parameters. Results of ongoing and future clinical trials evaluating fixed-duration combinations with BTK inhibitors and novel agents are awaited.

This is the first independent validation of our previously reported multi-omic driven WM subtype classification. The studies underscore that epigenetic differences underlie the biology of WM subclassification and support a strong role for epigenetic changes driving WM evolution.

Novel transcripts identified by PacBio IsoSeq analysis drive expression of key genes including the important MAPK/ERK regulator DUSP22, and FC receptor FCRLB that promotes survival of B-lymphocytes. Other genes of interest included modulators of chromatic accessibility. Our findings demonstrate important new insights into isoform usage associated with WM subtype in WM and provide novel insights into the underlying biology of the disease.

Patients received the 28-day cycle of Rituximab (375 mg/m2 IV on day 1), Bortezomib (1.3 mg/m2 SC on day 1, 8, 15), Lenalidomide (15 mg per oral day 1-21) and dexamethasone (20 mg iv or oral day 1-4). R-VRD regiment could be helpful for MYD88 mutation negative or CXCR4 mutation positive patients. BTK inhibitors show superior response and survival outcomes for patients with MYD88 mutation positive and CXCR4 mutation negative. So, we are supposed that R-VRD could be optional treatment for patients who are not suitable for BTK inhibitors.