TP53 mutation + Chr del(17p)

Considering that TP53 alterations accumulate during MM progression and are associated with drug resistance even in the context of novel therapies, our study further emphasizes the need for routine evaluation of both del(17p) and TP53 mutations. Patients with multi-hit TP53 should be prioritized for inclusion in trials of novel therapeutic strategies.

This new strategy, along with the improved tolerability of these agents, offers particular benefit to older and frail patients, with dosing tailored to comorbidities and concomitant therapies.Given the heterogeneity in older patients' health status, geriatric assessments (e.g., CIRS, FRAIL score) are additional key for individualized therapy decisions and adverse events influence therapy choice (e.g. cardiovascular risk with BTK inhibitors. Beyond clinical factors, patient preferences-such as opting for continuous (e.g., BTK inhibitor monotherapy) versus time-limited therapy (e.g., venetoclax plus obinutuzumab or ibrutinib plus venetoclax)-and treatment tolerability are decisive.

P1/2, N=144, Recruiting, AVM Biotechnology Inc | Trial completion date: Jun 2025 --> Dec 2026 | Trial primary completion date: Apr 2025 --> Apr 2026

Recent advancements in Bruton's tyrosine kinase (BTK) inhibitors like acalabrutinib and zanubrutinib offer improved efficacy and safety profiles, impacting treatment choice for all patients namely elderly patients with comorbidities. Targeted therapy is preferred for most patients, with geriatric assessment pivotal for treatment decisions. Second-generation drugs aim to improve outcomes both in efficacy and safety, advocating for a patient-centered approach in clinical studies.

Among SR patients according to the genomic definition with normal creatinine, median PFS of those with high beta2-microglobulin was not significantly different from patients with normal beta2-microglobulin level. This study validates the IMS/IMWG genomic definition of high-risk myeloma in a large cohort of patients diagnosed from 2019.

Moreover, treatment paradigms are shifting toward earlier integration of immunotherapy, and therapeutic strategies are individualized based on refined molecular risk profiles and clone dynamics. Therefore, a correct definition of HRMM could help in significantly improving both clinical and therapeutic management of a subgroup of patients with an extremely aggressive disease.

Zanubrutinib + venetoclax demonstrated impressive efficacy and a favorable safety profile in patients with TN CLL/SLL, regardless of the presence of TP53-aberrant disease.

P1/2, N=7, Completed, Iovance Biotherapeutics, Inc. | N=70 --> 7 | Trial completion date: Sep 2025 --> Dec 2024 | Trial primary completion date: Sep 2025 --> Nov 2024 | Active, not recruiting --> Completed

These consensus statements provide practical recommendations for the current manage-ment of TN CLL patients in Singapore and similar healthcare systems based on up-to-date evidence. Regular updates to treatment guidelines are important to ensure responsiveness to emerging evidence and evolving clinical practices and to improve patient outcomes and quality of life.

In very frail patients, supportive treatment should be considered. In relapse/refractory patients, prior treatment, the biological risk of CLL, the duration of response (if prior finite treatment), or the reason for stopping BTKi (if prior continuous treatment) should be considered.

Introduction : The combination of venetoclax, the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL) (Wierda et al. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall response rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing at approximately 230 study sites in 20 countries, including 50 sites in the US, 6 in Brazil, and 15 in Canada.

Introduction : Combined treatment with covalent BTK-inhibitor (cBTKi), such as ibrutinib, acalabrutinib, or zanubrutinib with BCL2-inhibitor, venetoclax, +/- CD20 monoclonal antibody obinutuzumab showed high rates of undetectable MRD (U-MRD4, 10-4 sensitivity) remission in patients (pts) with CLL (Jain, NEJM 2019; Munir NEJM 2023; Wierda, JCO 2021; Kater, NEJM Evidence 2022). Adverse event profile was similar to what was noted in previous studies with these agents. Updated data will be presented.