In a groundbreaking real-world study, researchers have unveiled compelling evidence supporting the efficacy and safety of selinexor-based regimens as first-line treatments for elderly patients grappling with diffuse large B-cell lymphoma (DLBCL). This progressive hematologic malignancy, notorious for its aggressive nature and poor prognosis in older populations, has long posed significant therapeutic challenges. The study, conducted at the Sun Yat-sen University Cancer Center, delivers vital insights that could shift current treatment paradigms and improve survival outcomes for this vulnerable cohort.
Diffuse large B-cell lymphoma remains one of the most common and lethal types of non-Hodgkin lymphoma worldwide. Its incidence escalates with age, rendering elderly patients particularly susceptible to adverse outcomes and treatment-related toxicities. Historically, therapeutic regimens for older patients have been limited by frailty, comorbid conditions, and decreased tolerance to chemotherapy, underscoring the urgent necessity for innovative, less toxic yet efficacious treatment options.
Enter selinexor, a first-in-class selective inhibitor of nuclear export (SINE) compound targeting exportin 1 (XPO1). By impeding XPO1, selinexor prevents the nuclear export of tumor suppressor proteins and oncogenic mRNAs, thereby reactivating tumor-suppressive pathways and inducing apoptosis in malignant cells. This novel mechanism of action has sparked intense research interest due to its potential to offer an alternative line of attack against resistant or refractory cancers, especially in patients for whom standard chemotherapies prove intolerable.
The retrospective analysis encompassed 16 elderly patients with DLBCL, aged between 60 and 80, who received selinexor-based regimens as their initial systemic therapy between late 2021 and mid-2023. Of particular note, the cohort displayed a balanced gender distribution, with 43.8% male and 56.2% female patients. Despite the advanced age and associated treatment challenges, the outcomes revealed an extraordinarily high objective response rate (ORR) of 93.8%, with complete response (CR) observed in over 80% of cases.
Remarkably, all patients (n=5) administered chemotherapy-free selinexor combinations attained complete remission, shedding light on the potential for this drug to circumvent the toxicities commonly encountered with cytotoxic agents. The median follow-up period of 8.5 months, though modest, allowed for preliminary preliminary evaluation of durability, with a median progression-free survival (PFS) not reached and a promising 1-year PFS rate approaching 80%. These results underscore selinexor’s capacity to deliver sustained disease control in a population notoriously difficult to treat.
Digging deeper into the data, the subset of patients aged 75 and above demonstrated a remarkable 100% complete response rate, hinting at selinexor’s enhanced therapeutic role in the oldest and most fragile lymphoma patients. This finding is particularly compelling given the historical exclusion of elderly and frail patients from clinical trials, which often limits the generalizability of novel therapies. Selinexor thus emerges as a beacon of hope, potentially bridging this critical treatment gap.
Safety and tolerability, paramount in this delicate patient population, were meticulously monitored. Hematologic adverse events were the most frequently observed, with leukopenia affecting over 90% of patients and neutropenia observed in over 80%. Although such cytopenias evoke caution, the study reported that these side effects were manageable and reversible with standard supportive measures. Importantly, non-hematologic toxicities such as nausea, vomiting, fatigue, and decreased appetite were predominantly mild to moderate and effectively controlled.
The study’s real-world design lends practical significance, reflecting clinical scenarios outside the controlled environment of randomized trials. This approach captures the complexities and diverse comorbidities typical of elderly lymphoma patients, enhancing the external validity of the findings. Consequently, oncologists can interpret these data as more reflective of actual clinical practice, potentially expediting the adoption of selinexor-based therapies.
Understanding the pharmacodynamics of selinexor elucidates why it may be uniquely suited to DLBCL treatment in elderly populations. By selectively trapping key regulatory proteins in the nucleus, selinexor reinstates apoptotic signaling pathways that malignant B cells often evade. This targeted molecular approach contrasts with the broad cytotoxicity of conventional chemotherapy, offering a more refined means of combatting cancer while preserving patient quality of life.
The study does not come without limitations, primarily its relatively small sample size and short follow-up duration. Nevertheless, the high response rates and favorable safety profile lay the groundwork for larger, prospective clinical trials to confirm these promising outcomes and explore combinational regimens or sequencing strategies that may optimize patient benefit.
Elderly DLBCL patients frequently face a therapeutic conundrum — balancing efficacy against the risk of debilitating side effects that may compromise overall health and independence. Selinexor-based regimens, especially those administered without concurrent chemotherapy, represent a paradigm shift towards personalized, tolerable, yet potent cancer care, potentially redefining first-line therapy standards for this population.
Moreover, the mechanistic insights from this investigation embolden future research into exploiting nuclear export inhibition beyond DLBCL, broadening therapeutic horizons across various hematologic and solid malignancies. The reuse of selinexor in combination with other targeted agents or immunotherapies could unlock synergistic anti-tumor effects, a prospect warranting further scientific exploration.
Clinicians seeking to improve outcomes in elderly patients with aggressive lymphomas now have a promising new tool in selinexor. Its incorporation into treatment algorithms could alleviate the historic under-treatment of aged patients, address unmet medical needs, and ultimately enhance survival and quality of life — the dual pillars of modern oncology care.
In summary, this pioneering real-world study reports remarkably high rates of deep and durable responses coupled with manageable toxicity profiles in elderly DLBCL patients treated with selinexor-based regimens. These findings bolster confidence in nuclear export inhibition as an innovative therapeutic avenue and advocate for its expanded clinical evaluation and utilization.
As the oncology community continues to grapple with the complexities of treating aged, comorbid patients with aggressive cancers, selinexor’s emergence offers renewed hope. With further validation, it may soon become the cornerstone of geriatric lymphoma therapeutics, exemplifying the power of precision medicine to transform outcomes in even the most challenging clinical contexts.
The journey to establishing selinexor as a standard first-line treatment in elderly DLBCL patients is underway, and this study represents a vital milestone. Ongoing research promises to refine dosing strategies, identify biomarkers predictive of response, and optimize patient selection to maximize benefit and safety. The future of lymphoma care for the elderly is brighter than ever.
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Subject of Research: Efficacy and safety evaluation of selinexor-based regimens as first-line treatments in elderly patients with diffuse large B-cell lymphoma (DLBCL).
Article Title: Efficacy and safety of selinexor-based regimens as first-line treatments for elderly patients with diffuse large B-cell lymphoma: a real-world study.
Article References:
Li, J., Ge, J., Chen, T. et al. Efficacy and safety of selinexor-based regimens as first-line treatments for elderly patients with diffuse large B-cell lymphoma: a real-world study. _BMC Cancer_ 25, 878 (2025). https://doi.org/10.1186/s12885-025-14295-6
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-14295-6
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