Pinto, Antonio, Carmelo Carlo-Stella, Monia Marchetti, et al. 2025. “Defining and Addressing the Current Unmet Medical Needs for the Frontline Treatment of Advanced Stage Aggressive Large B-Cell Lymphoma: A Perspective From an Ad Hoc Panel of Italian Experts,” Hematological Oncology 43: e70152. https://doi.org/10.1002/hon.70152.
In the article, there were errors in the author byline and Figure 3.
In the author byline, the author name “Marco Laddetto” was incorrect and should be “Marco Ladetto”.
Figure 3 was not the final version and should have been updated with the new figure as shown below.
We apologize for these errors.
Chimeric antigen receptor T (CAR-T) cell therapies have revolutionized the treatment of hematological malignancies, achieving high response rates in patients with relapsed or refractory disease. Despite these benefits, CAR-T cell therapies are associated with unique toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune cell-associated hematotoxicity (ICAHT), and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), which is characterized by a rare and life-threatening hyperinflammatory response. This paper presents a case of a 56-year-old woman with relapsed mantle cell lymphoma (MCL) treated with the CAR-T cell therapy, brexucabtagene autoleucel, who had subsequently developed CRS and later IEC-HS. Initial management included tocilizumab, corticosteroids, and anakinra, followed by the compassionate use of emapalumab, an interferon-γ blocker. To provide broader context, we conducted a literature review of CAR-T cell-related toxicities, focusing on IEC-HS and its management with emapalumab. Clinical and laboratory manifestations, such as elevated ferritin levels, cytopenias, and organ dysfunction, underpin the diagnostic criteria for IEC-HS. Vigilant monitoring and tailored therapeutic approaches are required to effectively manage toxicities associated with CAR-T cell therapy, to maximize its benefits and minimize adverse effects. In more severe IEC-HS cases, emapalumab may be used as an effective targeted therapy.
The introduction of pediatric-inspired chemotherapy protocols for acute lymphoblastic leukemia (ALL) in the setting of adult patients affected by lymphoblastic lymphoma (LL) has improved the results in terms of outcomes. Within the Campus ALL network, we retrospectively collected data on 50 LL-patients from 23 hematology centers in Italy treated according to the GIMEMA LAL1913 protocol, with the aim of confirming the ALL results and of testing the effectiveness of an approach based on higher cumulative doses of the non-myelosuppressive components such as steroids and pegylated asparaginase, in addition to earlier and more intensive central nervous system prophylaxis. After cycle 3 (high dose methotrexate and cytarabine, C3), the cumulative incidence (CI) of PET-based complete response (CR) was of 83% (median time to response from protocol start: 3.7 months; CI95%: 3.1–4.2). With a median follow-up of 27.5 months, the 2-year overall survival (OS), disease free survival (DFS) ed event free survival rates were of 77%, 76% and 69%, respectively. The 2-year CI of relapse was of 26%. Multivariable analysis identified ECOG ≥ 2 as an independent prognostic factor for OS (HR = 3.279; CI95% 1.035–10.389, p = 0.044) and DFS (HR = 13.00, ICI95%: 3.383–57.909, p < 0.001), respectively. No significant impact was observed for pegylated asparaginase dose (reduced and/or omitted versus (vs.) full doses), age (≥ 55 vs. < 55), stage (0–I vs. II–IV), CD1a (negativity vs. other than CD1a negativity), bone marrow involvement (absent vs. ≤ 20%), or allotransplantation. The results of this study show the appropriateness of the LAL1913 protocol for the management of LL patients. Survival outcomes reflect those expected, although this drug combination was never tested before in a real-life setting. Taken together, these results suggest that LAL1913 might be considered as a reference protocol for the frontline treatment of adult LL patients.
Testing to discontinue imatinib already started some years after the advent of this new CML therapy. Since that time, despite many trials and studies in this field, there are still significant gaps, and many fundamental questions remain unanswered. Probably the most intriguing is the persistence of minimal residual disease, which does not lead to disease recurrence in all patients. Nevertheless, today's understanding enables TKI to be safely discontinued in eligible patients outside clinical trials. Notwithstanding, TKI cessation still has to be considered and indicated with caution, taking into account several important viewpoints, like: (i) why stop the therapy in a particular patient, and are all the eligible patients willing to cease the treatment? (ii) Will all the TKI-related side effects relieve upon stopping? (iii) are there any side effects after discontinuing treatment? This review covers extensively all aspects of treatment cessation, like history, theoretical background, eligible patients, monitoring after treatment discontinuation, trigger for retreatment, therapy restart, predictive factors for successful therapy cessation, immunological aspects, potential complications of TKI withdrawal, late molecular relapses, blast crisis development, kinetics of preexisting TKI-related side effects and laboratory values, and quality of life upon treatment cessation. The art of treatment cessation is to select the best candidate based on many diverse facts and information, and follow the patient in the most rational way with smartly anticipating the potential risks and side effects.
We investigated the course of fatigue, neuropathy, psychological distress and their impact on HRQoL among diffuse large B-Cell Lymphoma (DLBCL) survivors up to 13 years after diagnosis, and compared it to an age- and sex-matched population. DLBCL survivors diagnosed between 2004 and 2011, who survived ≥ 1 year were selected from the Netherlands Cancer Registry. Survivors completed annual questionnaires 2009–2019, including EORTC QLQ-C30, EORTC CLL-17 and the Hospital Anxiety and Depression Scale. Linear mixed models were used to assess symptom trends and HRQoL associations over time. 302 survivors (response rate 84%) completed a median of three questionnaires. Fatigue improved slightly over time but neuropathy and psychological distress remained unchanged; persistent symptoms were reported by 25%, 28%, and 23% of survivors, respectively. Having two or more comorbidities was associated with higher symptom levels (βfatigue = 7.8, p-value < 0.001; βneuropathy = 6.7, p-value = 0.003; βpsychological distress = 2.2, p-value < 0.001). Having received seven to eight cycles of (R-)CHOP14 was associated with higher neuropathy levels (β = 14.5, p < 0.001) and non-(R-)CHOP treatments were associated to high fatigue levels (β = 14.0, p-value = 0.02) and psychological distress (β = 4.3, p-value = 0.01). Higher symptom levels were associated with poorer HRQoL. One in four DLBCL survivors reported persistent fatigue, neuropathy or psychological distress, negatively impacting their HRQoL. Routine symptom monitoring is essential to identify needs and guide supportive care referrals.
Despite the survival benefit observed in recent decades, early mortality (EM) remains critical in newly diagnosed multiple myeloma (NDMM) patients, with heterogeneous definitions and risk factors across studies. Besides, prognostic models for predicting EM are limited, especially in real-world scenarios. This single-center retrospective study performed comprehensive analyses as well as risk prediction models of 1093 NDMM patients diagnosed between 2007 and 2021 in China, finding the EM rate was 5.9% at 2 months, 8.8% at 6 months and 13.3% at 12 months. Infection and cardiac events were documented as the top two most common causes of early death. Risk factors that were independent predictors of both EM and OS mainly included cardiac amyloidosis, stroke, del (17p) and poor performance status. ISS stage, platelet count, treatment regimen and concomitant cardiac disease influenced OS rather than EM. Multivariate model-based nomograms were constructed to estimate 2-month, 6-month, 12-month mortality, plus OS, enabling individualized outcome prediction, validated via receiver operating characteristic (ROC) and calibration curves. EM is associated with multiple factors in MM patients, and early identification of patients with higher risk of EM may translate into tailored management in clinical practice.
Lymphomas are common cancers affecting the lymphatic system. Chemotherapy is a standard treatment, yet its impact on patient's physical capacity remains understudied. This study aimed to evaluate changes in body composition, muscle strength, and physical performance in patients diagnosed with lymphoma undergoing chemotherapy and to explore the potential association between muscle function and treatment tolerability. This single-center prospective cohort study included participants aged ≥ 18 years scheduled for first-line anthracycline-based chemotherapy for aggressive lymphoma. Patients were recruited and tested before treatment and after 6 months. Body composition (DXA), hand-grip strength, 30 s Sit-To-Stand test, 10-m gait speed and Quality of Life (EORTC-QLQ-C30) were assessed. Low muscle strength, lean mass and gait speed were defined according to the European Working Group on Sarcopenia in Older People (EWGSOP2). Fifty-eight patients (42 males) with a median age of 62 years (range 18–87) completed both test points and were included in the analysis. From baseline to follow-up, total lean mass decreased by 1.70 kg (95% CI −2.55 to −0.85, p = 0.0002), body fat percentage increased by 2.3% (95% CI 1.19 to 3.41, p = 0.0001), handgrip strength decreased by 1.93 kg (95% CI −3.15 to −0.71, p = 0.002), whereas Sit-To-Stand performance increased by 1.4 repetitions (95% CI 0.15 to 2.69, p = 0.03). No changes were observed in appendicular lean mass, body weight, or gait speed. Further, there was no association between changes in muscle function and treatment tolerability. Significant declines in total lean body mass and muscle strength were observed from the start of chemotherapy to 6 months post treatment. These findings underscore the importance of routine muscle function screening and rehabilitation during and after chemotherapy for patients with lymphoma.
Aggressive large B-cell lymphomas (LBCL) include a range of disease types characterized by heterogenous histopathologic, molecular, and genetic features. In this review, we summarize the main standardized disease assessments, treatments and patient journey and we discuss some of the questions that we will face in interpreting and applying their results in clinical practice in the next few years. Specific methodologies borrowed from FDA clinical trials indications to settle the more important goals (both for fit and unfit patients) - key aspects to be considered in clinical management—were used. The Expert Panel was conceived to reach a consensus on defining unsettled and controversial issues while envisioning possible solutions for current challenges in treating newly diagnosed patients with advanced-stage LBCL not only in the Italian context but also for other Countries sharing similar health care system. The fast-evolving treatment scenario for LBCL holds promise of improving outcomes in these high-risk setting, and we eagerly await new treatment regimens to further optimize patient outcomes.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：