Clinical Lymphoma, Myeloma & Leukemia最新文献

The global incidence of multiple myeloma (MM) continues to rise. While survival rates for newly diagnosed patients have improved substantially with the introduction of novel therapies, outcomes remain poor for those with triple-class-exposed (TCE) relapsed/refractory MM (RRMM). Recent therapeutic innovations, including chimeric antigen receptor T-cell therapy, antibody-drug conjugates, and bispecific antibodies, offer new effective options for this challenging population. Teclistamab, the first approved B-cell maturation antigen-targeted bispecific antibody, has demonstrated deep and durable responses and an acceptable safety profile in TCE RRMM. Teclistamab is now a recommended treatment from second relapse onwards in patients with TCE RRMM in the 2025 European Hematology Association-European Myeloma Network guidelines. Nevertheless, considering the novelty of this agent and its overall safety profile, there is a need for clear guidance on patient management in routine clinical practice. Here, we aim to provide a comprehensive overview of the clinical profile of teclistamab and expert recommendations on its optimal use in TCE RRMM. We focus on key aspects and considerations needed for patient selection (including special populations such as the elderly, frail individuals, those with extramedullary disease or renal impairment), as well as therapy initiation, and strategies for adverse event prevention, monitoring, and management. Ultimately, this review aims to support physicians in maximizing the therapeutic potential of teclistamab, improving outcomes for patients through tailored, evidence-based management.

Background: Targeted therapies have replaced chemoimmunotherapy for chronic lymphocytic leukemia (CLL), but high-risk CLL patients with TP53 aberrations continue to represent a significant unmet medical need. We profiled treatment patterns, outcomes, and adverse effects in a large, unselected cohort of high-risk CLL patients.

Patients and methods: This study retrospectively analyzed clinical data from 1,720 CLL patients diagnosed between 2012 and 2023 within the Helsinki University Hospital district in Southern Finland. We focused on 543 patients who received first-line (1 L) systemic treatment.

Results: Of the 543 treated patients, 78 (14.4%) had a TP53 aberrations. A clear shift in treatment patterns occurred after 2018, with targeted therapies comprising over one-third of 1 L regimens. For high-risk patients, ibrutinib use at the 1 L stage rose dramatically after 2018, replacing chemoimmunotherapy as the most common treatment. This change coincided with a marked increase in the median time-to-next-treatment (TTNT) for high-risk patients, from 21.2 months (2012-2017) to 26.0 months (2018-2023). Increased TP53 and IGHV mutation testing rates facilitated more personalized treatment approaches over time. Adverse events were less frequent in patients receiving targeted therapies (62.1%) compared to those on non-targeted regimens (73.5%). Despite these improvements, the median overall survival (OS) for high-risk patients remained challenging at 47.1 months after 1 L treatment.

Conclusion: The transition to targeted therapies has improved outcomes for high-risk CLL patients. Nevertheless, outcomes for high-risk CLL patients remain inferior to those reported in clinical trials, underscoring the need for real-world evidence and improved therapies.

COVID-19 is a threat to patients with hematological malignancies (HM) even in the Omicron era, because mortality rates are still high in HM patients, and a significant number of patients develop a protracted disease course called "persistent COVID-19 (pCOVID-19)" which can continue for weeks to months. pCOVID-19 can be life-threatening by itself, but also drastically affects the disease course of the underlying HM by delaying or terminating chemotherapy. Also, patients with pCOVID-19 can be potentially contagious, and timing of ending isolation is a dilemma the hematology ward faces. Furthermore, pCOVID-19 has been reported to lead to acquisition of SARS-CoV-2 multidrug-resistant mutations, which is an alarming issue for both the patient and public health. The optimal management method of pCOVID-19 is currently unknown, and because HM patients are excluded from randomized clinical trials, evidence is limited to case reports and small case series. We carried out a comprehensive literature review of Omicron pCOVID-19 occurring in HM patients, compiled the scattered evidence, and provide practical recommendations which can be of guide to clinicians. Main topics discussed within this review include efficacy of vaccinations in HM patients, risk factors for developing pCOVID-19 (B-cell depleting agents, bendamustine + rituximab therapy, bispecific T-cell engagers, etc.), treatment of pCOVID-19 including extended/sequential/combination therapy incorporating antivirals (nirmatrelvir/ritonavir, remdesivir, molnupiravir, and ensitrelvir) and convalescent plasma/intravenous immunoglobulin therapy, monitoring pCOVID-19 with reverse transcription (RT)-PCR, and optimal target cycle threshold values as goals of therapy.

Background: Epstein-Barr virus (EBV)-positive nodal T- and natural killer (NK)-cell lymphoma (EB-nTNKL) is a newly defined, rare, and aggressive EBV-driven lymphoid malignancy that typically affects older individuals, predominantly male, of East Asian descent. It is characterized by a cytotoxic T-cell phenotype, with only a limited number of cases documented to date.

Methods: We performed a multicenter retrospective analysis of 11 patients diagnosed with EB-nTNKL via lymph node biopsy in Japan in order to better characterize its clinicopathological features and outcomes.

Results: The median age at diagnosis was 65 years (range 24-81), and most patients presented with advanced-stage (III/IV) disease, B symptoms, and high-risk International Prognostic Index scores. Elevated serum lactate dehydrogenase (median 614 U/L) and soluble interleukin-2 receptor (median 5247 U/mL) levels were observed in all cases. All cases expressed cytotoxic molecules (granzyme B and/or TIA-1), indicating a cytotoxic T/NK-cell phenotype, and 8 cases were CD8-positive. Responses to conventional chemotherapy were poor. The median overall survival was only 2.9 months, with 6 of 11 patients dying within 3 months of diagnosis.

Conclusions: EB-nTNKL represents a distinct clinicopathological entity with a fulminant clinical course and profound chemoresistance, resulting in an extremely poor prognosis. However, differentiation from other EBV-associated T/NK-cell neoplasms, particularly those arising in younger patients, remains a diagnostic challenge and warrants further clinicopathological investigation. These dismal outcomes underscore an urgent need to develop more effective therapeutic strategies.

Introduction: Financial difficulty among patients with multiple myeloma (MM) is linked to reduced treatment adherence and worse outcomes. However, it is usually measured through patient questionnaires, which may be inconsistently offered or poorly completed. We hypothesized that credit data could detect financial difficulty and assessed its relationship with treatment outcomes.

Methods: We conducted retrospective analyses using an integrated database with cancer registry data, insurance claims, and credit data for Western Washington State patients with MM diagnosed between 2012 to 2020. Financial difficulty was categorized into 4 tiers using credit attributes at diagnosis ("financial fragility") and during 2-year follow-up ("financial hardship"). We examined associations between financial fragility and suboptimal treatment, and identified predictors of financial hardship.

Results: Among 396 MM patients, 35%, 38%, 5%, and 20% had no, mild, moderate, and severe financial fragility at diagnosis. Those with moderate/severe fragility were more likely to have delayed treatment initiation or interruptions (OR 1.67, 95% CI, 0.99-2.81, P = .06). Among 290 patients with 2-year follow-up, 69% showed no change in financial hardship from baseline. Financial fragility at diagnosis strongly predicted higher levels of future hardship (OR: 25.0, 95% CI, 11.17-56.13, P < .001). Patients receiving autologous transplant within the first year had lower odds of future hardship (OR 0.33, 95% CI, 0.12-0.90, P = .03).

Discussion: Financial fragility at diagnosis is associated with suboptimal MM treatment and predict future hardship. Credit data could offer an alternative method to identify patients at risk.

Glyphosate-based formulations (GBFs), such as Roundup, are the most heavily used herbicides in the world. In 2015, the International Agency for Research on Cancer (IARC) concluded that glyphosate and GBFs are probably carcinogenic to humans (group 2A), mainly for non-Hodgkin lymphoma (NHL). However, this finding has been controversial and most pesticide regulatory agencies have not followed their lead. The purpose of this review is to update the scientific literature linking exposure to glyphosate and GBFs to the development of NHL, with emphasis on new findings over the last 5 years. The recent epidemiologic studies provide new evidence for an association between exposure to GBFs and an increased risk of NHL. A new animal study has also shown that glyphosate and GBFs are carcinogenic in rats and also cause acute leukemia. Mechanistic studies have continued to demonstrate that glyphosate and GBFs are genotoxic to human lymphocytes and other cells. Genotoxic and other biological effects have also been shown in human studies and in various animal and cell models with these agents even at low doses. A novel mechanism of chelation and sequestration of glyphosate in bone with slow release over days to weeks resulting in prolonged bone marrow and blood exposure may lead to the development of acute leukemia and other hematologic malignancies. These new findings continue to provide consistent, coherent and compelling evidence that glyphosate and GBFs are a cause of NHL in humans exposed to these agents, and should prompt new reviews by pesticide regulatory agencies around the world.

The transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma, termed Richter transformation (RT), continues to be the unmet need for patients with chronic lymphocytic leukemia (CLL). There remains no standard of care treatment for RT, where survival after the diagnosis is short. However, there have been recent developments in the study of RT, where incidence may be decreasing, prognostic factors of survival are being redefined, and novel treatments have been developed. These studies may have moved the needle on outcomes for patients with RT, providing hope to physicians and patients alike. In this review article, we discuss these recent findings related to RT in the modern era of therapy, highlighting our approach to treatment and interesting RT designated trials that are ongoing.

Background: In multiple myeloma, t(11;14) confers a unique biology including a lymphoplasmacytic phenotype and an association with plasma cell leukemia. Some studies report a favourable while others a worse prognosis, compared to non-t(11;14) cases. Dependence of t(11;14) cells on the BCL2 pathway offers a potential therapeutic target.

Methods: We performed a matched comparison of real-world outcomes in patients with and without t(11;14) as a benchmark for future therapy targeting BCL2. A retrospective observational study was conducted using the Canadian Myeloma Research Group database between 2004-2022. FISH and karyotype studies were used to identify which patients carried the t(11;14) versus those who did not. Those found to harbour the t(11;14) were matched one-to-one with a non-t(11;14) cohort based on age at line 1 of therapy, gender, year of diagnosis and history of autologous stem cell transplant.

Results: Compared with non-t(11;14), those with t(11;14) had similar PFS during line 1 (44 (95%CI: 32-51) months vs. 44 (95%CI: 36-65) months), but shorter PFS in line 2 (18 (95% CI: 11-22) months vs. 32 (95%CI: 23-49) months) resulting in a shorter PFS2 (55 (95%CI: 45-87 months vs. 83 (95%CI: 74-115) months).

Conclusions: Although not yet translating into a worse OS, this merits longer follow up. This suggests the need for optimal treatment choice and sequencing at relapse within this unique cytogenetic group. Our large, matched comparison in real-world t(11;14) myeloma serves as an important benchmark for studies looking at targeted BCL2 inhibitors in these patients.

Background: Frontline therapy fails to cure ∼ 25% of patients with large B-cell lymphoma (LBCL), underscoring the need for clinical trials to improve outcomes. However, enrollment remains limited by logistical and structural barriers. Investigator-initiated trials (IITs) at our center enroll patients 5 to 10 times faster than industry-sponsored trials, yet the influence of geography and socioeconomic status on participation remains poorly understood.

Methods: We retrospectively reviewed adults with newly diagnosed large B-cell lymphoma (LBCL) referred to Fred Hutchinson Cancer Center (FHCC) between October 2022 and June 2024. Patients were prescreened by a clinical research nurse and investigators for frontline IIT eligibility. Demographic, geographic, and socioeconomic data were collected, including sex, race, ethnicity, distance from FHCC, area deprivation index, insurance, and interpreter need. Logistic and elastic net regression were used to evaluate predictors of trial enrollment. Trial-ineligible patients were analyzed descriptively.

Results: Of 153 patients, 68 (44%) were trial-eligible; 24 (35%) enrolled. Enrolled patients lived closer to FHCC (median 15 vs. 50 miles; P = .00015) and had lower ADI scores (median 8 vs. 21; P = .006) than non-enrolled eligible patients. In univariate analysis, both distance and ADI were associated with enrollment; in multivariable stepwise regression, only distance remained significant. Elastic net regression identified both distance and ADI as frequently selected predictors. Among 85 trial-ineligible patients, 61% had already initiated treatment; these patients also lived farther away and in more deprived areas.

Conclusion: Geographic distance and neighborhood deprivation significantly influenced trial enrollment, even in investigator-initiated trials (IITs). Decentralized trial models, telemedicine triage, and system-level interventions are needed to reduce these inequities.

Background: Philadelphia-negative B-cell acute lymphoblastic leukemia (Ph- B-ALL) remains a therapeutic challenge in adults. Cytogenetic abnormalities and measurable residual disease (MRD) are key prognostic markers, but their integration with allogeneic hematopoietic stem cell transplantation (HSCT) is not well defined.

Materials and methods: This single-center retrospective study analyzed 368 adult Ph- B-ALL patients, classifying them into 9 cytogenetic subgroups. We evaluated the prognostic effect of high-risk cytogenetics (KMT2A-rearranged, 14q32/IGH, t(1;19)) and MRD status on outcomes, with particular focus on HSCT's modifying role.

Results: Without HSCT, patients with high-risk cytogenetics had significantly inferior 3-year survival compared with cytogenetically normal patients (overall survival (OS): 24.3% vs. 56.5%, P < .001; disease-free survival (DFS): 8.3% vs. 41.4%, P < .001). HSCT eliminated these disparities, yielding comparable outcomes between high-risk and normal subgroups (post-HSCT OS 76.9% vs. 70.8%, P = .603). MRD positivity after consolidation independently predicted relapse in nontransplant patients (HR 3.29, 95% CI, 1.31-8.27, P = .012) but not after HSCT. Reduced-intensity conditioning was associated with worse DFS compared with myeloablative regimens (HR 2.51, 95% CI, 1.24-5.10, P = .011).

Conclusion: Our results support a dual approach: HSCT for patients with high-risk cytogenetics or MRD positivity, and MRD-guided therapy for those not eligible for transplant. These findings reinforce risk-adapted strategies and lay the groundwork for future trials combining genetic and MRD-guided management in Ph- B-ALL.