Recenti progressi in medicina最新文献

In transplant-ineligible patients with multiple myeloma (MM), disease relapse represents a critical step in the therapeutic pathway. The increasingly early use of frontline regimens containing anti-CD38 monoclonal antibodies has led to significant improvements in clinical outcomes, while simultaneously increasing the complexity of treatment selection in subsequent lines, particularly in elderly and frail patients. Current guidelines recommend the use of combination regimens based on triplets in the second-line setting, preferably incorporating mechanisms of action different from those previously employed. In this context, selinexor, an oral selective inhibitor of exportin-1 (XPO1), represents an innovative therapeutic option due to its ability to restore tumor suppressor protein activity and enhance the efficacy of other antimyeloma agents, including proteasome inhibitors. Data from the phase III BOSTON trial demonstrated that the selinexor-bortezomib-dexamethasone (SVd) combination is associated with a clinically meaningful benefit in terms of progression-free survival and overall survival in patients with relapsed MM, with a particularly relevant advantage in patients treated in the second-line setting who were not previously exposed to bortezomib. Overall, the SVd regimen may represent an effective and sustainable second-line therapeutic strategy, capable of combining antitumor activity with manageable tolerability, and addressing the clinical needs of a patient population increasingly representative of contemporary hematologic practice.

CAR-T therapies represent a major advance in the management of large B-cell lymphomas. Axi-cel, the only product approved in Italy as a second-line treatment, demonstrated superiority over standard therapy in the randomized phase 3 ZUMA-7 trial. We report the case of a 66-year-old woman with large B-cell lymphoma, diagnosed at stage IV with a high disease burden. After achieving complete remission with first-line R-CHOP, she experienced an early relapse at 6 months. She was therefore selected for axi-cel CAR-T therapy, preceded by leukapheresis and one cycle of R-DHAP, resulting in a partial response. The patient developed only grade 1 CRS and grade 1 early ICANS, both easily managed. PET scans at 1, 3, and 6 months showed a complete metabolic response, which is ongoing with no long-term toxicities. This case underscores the importance of close follow-up and timely CAR-T eligibility in high-risk patients.Key words. Axi-cel, CAR-T, LBCL, second line.

HER2-positive breast cancer accounts for approximately 15-20% of all breast tumors and is characterized by a more aggressive biology compared with other subtypes. However, the introduction of anti-HER2 agents has made this disease increasingly manageable, even in advanced stages. Among the most recent therapeutic advances, trastuzumab deruxtecan (T-DXd) has emerged as a new standard of care, thanks to its remarkable efficacy, ability to induce deep and durable responses, and significant activity in challenging sites such as the central nervous system and bone. Clinicians play a crucial role in ensuring optimal patient management during T-DXd therapy, including the monitoring and prevention of major toxicities (such as interstitial lung disease, nausea and vomiting, and cardiotoxicity), as well as in evaluating potential combinations with locoregional treatments - within an increasingly integrated multidisciplinary team. Maintaining a good quality of life remains essential, particularly for patients achieving long-lasting responses. Finally, results from recent clinical trials suggest a potential role for T-DXd in earlier disease stages, underscoring the growing need for clinical expertise in managing this innovative therapy.