Treatment Of Lymphoma Research Articles

Risk of cardiovascular disease in Hodgkin lymphoma patients

Abstract Background Cardiovascular diseases are recognized as some of the most common and problematic late complications to the treatment of Hodgkin lymphoma (HL). However, the anticipated risk is predominantly based on studies of patients treated several decades ago with treatment regimens considered outdated by todays standard. Purpose To describe the risk of cardiovascular disease in HL patients undergoing contemporary treatment regimens and comparing this risk to matched comparators. Methods A register-based cohort study including all Danish HL patients ≥18 years at diagnosis, treated with anthracycline-containing chemotherapy between 2000 and 2022. Index date was defined as date of HL diagnosis. Matching with comparators from the background population was performed in a 1:5 ratio on age, sex, and comorbidities. Patients and comparators with malignancy and/or heart disease prior to the index date were excluded. The primary outcome was a composite endpoint of cardiovascular diseases: heart failure, ischemic heart disease, diseases of the aortic-, mitral-, and tricuspid valve, constrictive pericarditis, cardiomyopathies, atrial and ventricular arrythmias, or any invasive procedures related to these diagnoses. Follow-up began at index date and ended upon event, relapse, death, emigration, or end of follow-up (December 31, 2022), whichever occurred first. The cause-specific cumulative incidence of the primary outcome was computed with all-cause death and lymphoma relapse as competing events using the Aalen-Johansen estimator. Exploratory multivariable Cox regression analyses were performed to identify risk factors for cardiovascular disease among patients with HL. Risk factors were adjusted for sex, age, and comorbidities. Results A total of 1,917 HL patients and 9,585 matched comparators were included. Median age at diagnosis was 39 years (interquartile range [IQR]: 27-56), 57% were male, and median follow-up time was 10.2 years (IQR: 5.3-15.5). The majority of patients were treated with ABVD (83%) and the estimated median cumulative anthracycline dose was 250 mg/m2 (IQR: 200-300). During the study period, 50% of patients received radiotherapy. The cause-specific cumulative incidence of the primary outcome was higher among HL patients compared with comparators across follow-up: 3.7% (95% confidence interval: 2.8-4.6) vs. 2.0% (95% CI: 1.7-2.3) at 5 years, 7.2% (95% CI: 5.7-8.7) vs. 4.6% (95% CI: 4.1-5.1) at 10 years, and 14.2% (95% CI 11.6-16.9) vs 6.7% (95% CI: 6.0-7.5) at 15 years (Figure 1). Risk factors associated with development of heart disease in HL patients were history of hypertension (HR=1.81, 95% CI 1.15-2.84) and male sex (HR=2.01, 95% CI 1.39-2.91) (Figure 2). Conclusions The long-term risk of cardiovascular disease is still high in patients with HL after contemporary treatment suggesting that the use of modern radiotherapy has not eliminated the excess risk of cardiovascular disease.

Comparison of tucidinostat with CHOP-like versus CHOP-like in first-line treatment of peripheral T-cell lymphoma: a single-center real-world study.

Tucidinostat has been approved by the Chinese FDA for relapsed/refractory Peripheral T cell lymphoma (PTCL), but its efficacy in newly diagnosed PTCL has not been confirmed. In this study, we aimed to compare the efficacy of tucidinostat combined with CHOP-like (C + CHT) versus CHOP-like alone (CHT) in newly diagnosed PTCL patients. Of the PTCL patients, 109 were newly diagnosed. Patients in the C + CHT group who achieved objective response received tucidinostat maintenance therapy. A total of 36 pairs (n = 72) were matched at a ratio of 1:1 using propensity scoring. The matching criteria included: whether the Prognostic index for the peripheral T-cell lymphoma-not otherwise specified subtype (PIT) was ≥ 2, the pathological subtype, age > 60 years, and gender (matching tolerance = 0.024). A significantly higher objective response rate (ORR) (P = 0.016), 2-year progression-free survival (PFS) (P = 0.026), and 2-year survival rate (P = 0.017) was observed for the C + CHT group as compared to the CHT group. After propensity score matching (PSM), the C + CHT group as compared to the CHT group displayed significantly longer PFS (P = 0.035) and overall survival (OS) (P = 0.029). For the C + CHT group in the per-protocol set, the effect values showed a significant benefit in terms of both PFS (P = 0.027) and OS (P = 0.019). Common grade 3-4 haematological adverse events (AEs), had comparable incidence in each group; while common non-haematological AEs, including elevated AST and ALT were higher in the C + CHT group than in the CHT group. Our study suggests that the tucidinostat with CHOP-like regimen and sequential tucidinostat maintenance after objective remission provides a promising therapeutic approach for treating newly diagnosed PTCL patients.

BTKi combined with chemical immunotherapy in the initial treatment of aggressive mantle cell lymphoma: A retrospective study.

To explore the safety and efficacy of Bruton's tyrosine kinase inhibitor (BTKi) combined with immunological therapy in untreated patients with aggressive mantle cell lymphoma. A retrospective study was conducted on 9 previously untreated patients who received BTKi combined with immunological therapy, which means using immunological therapy and BTKi at the same time. The median age of the patients was 61 years, 7 were males, and the median follow-up time was 14 months. Among the 7 evaluable patients, the median follow-up was 14 months, and the objective remission rate was 100% (complete remission rate 86%, partial remission rate 14%), while the median progression-free survival and overall survival were not achieved. No patients were dead. The progression-free survival rate of 6 patients in the low-risk group was 100%. The combination of BTKi and chemoimmunotherapy has shown excellent therapeutic results in untreated patients of aggressive mantle cell lymphoma. At the same time, it also can prolong the survival time of high-risk patients. The combined therapy has acceptable safety in previously untreated patients. Hematological toxicity is the most common side effect and infection is the second one. A rash reaction was seen occasionally. There are no heart-related adverse events in the study. There are no new adverse effects caused by the combined treatment.

Risk factors for a decrease in bone mineral density in patients with Hodgkin's lymphoma.

BACKGROUND: Osteoporosis is characterized by a discharge of bone mass, which contributes to the development of pathological fractures. Hodgkin's lymphoma can cause a violation of bone microarchitectonics. The development of Hodgkin's lymphoma is characteristic of young people, on average from 16 to 35 years old. Early diagnosis of osteoporosis in young patients with Hodgkin's lymphoma is an urgent issue due to a prolonged asymptomatic decrease in bone mineral density, with the development of pathological fractures. AIMS: to study the risk factors for a decrease in bone mineral density in patients with Hodgkin's lymphoma who received pathogenetic therapy. MATERIALS AND METHODS: the study included 63 patients with Hodgkin's lymphoma and 30 volunteers from the control group. All patients answered the questionnaire questions in order to identify risk factors for osteoporosis. Common risk factors included: gender, age, body mass index; fractures in the history of the patient and his immediate family; taking hormone replacement therapy, proton pump inhibitors, glucocorticosteroids; the presence of concomitant diseases; the presence of amenorrhea in women; physical activity level and calcium intake. Specific factors include the use of chemotherapy drugs for the treatment of Hodgkin's lymphoma. The data obtained were subjected to statistical analysis in order to identify the most significant risk factors. RESULTS: osteopenia and osteoporosis are a serious complication of antitumor therapy of Hodgkin's lymphoma in young people. Unfortunately, today a small number of researchers are engaged in the problem of identifying predictors of osteoporosis in young patients with Hodgkin's lymphoma. Because of this study, the most significant risk factors for the development of osteoporosis were identified, namely low physical activity, taking proton pump inhibitors and glucocorticosteroids, as well as the development of secondary postcytostatic amenorrhea in women. CONCLUSIONS: timely diagnosis and prevention of osteoporosis in young patients will prevent a decrease in bone mineral density and reduce the risks of early disability in this category of patients.

The evolving role of checkpoint inhibitors in the treatment of Hodgkin lymphoma

Since their initial approval as single agent therapy for multiply relapsed/refractory Hodgkin lymphoma (HL), the PD-1 inhibitors nivolumab and pembrolizumab have been incorporated into second-line salvage regimens, and they are being investigated in upfront therapy of newly diagnosed patients. As second-line therapy in combination with brentuximab vedotin or multi-agent chemotherapy, nivolumab and pembrolizumab provide high complete remission rates and durable progression-free survival after consolidative autologous stem cell transplant. Incorporation of these agents into frontline chemotherapy regimens is feasible, and early results from a Phase III trial of nivolumab-AVD compare favorably with the existing standard for advanced stage HL, brentuximab vedotin plus AVD. As nivolumab and pembrolizumab move into earlier lines of HL therapy, open research questions include the efficacy of checkpoint inhibitor regimens in patients who relapse after frontline exposure to nivolumab or pembrolizumab; the selection of patients with relapsed HL who can achieve durable remissions without autologous stem cell transplant; and the efficacy of the PD-1 inhibitors in the frontline therapy of patients with early stage Hodgkin lymphoma.

Comparison of CHOP-19 and CHOP-25 for treatment of peripheral nodal B-cell lymphoma in dogs: A European multicenter retrospective cohort study.

Peripheral nodal B-cell lymphomas (PNBCL) represent the most common presentation of lymphomas in dogs. Multiagent CHOP (C = cyclophosphamide, H = hydroxydaunorubicin [Doxorubicin], O = Oncovin, P = prednisolone)-based chemotherapy protocols have been widely accepted as gold standard 1st-line treatment. CHOP-25 and CHOP-19 are most commonly prescribed but have never been directly compared. Our primary aim was to compare outcomes of dogs diagnosed with PNBCL, treated using a 1st-line CHOP-19 or CHOP-25 protocol. A secondary objective was to determine the impact of protocol-related variables on outcomes. Five hundred two dogs from 16 European oncology referral centers. One hundred fifty-five dogs were treated with CHOP-19 and 347 dogs with CHOP-25. Retrospective, multicentric cohort study of dogs diagnosed with PNBCL between 2014 and 2021. The 6-month, 1-year, and median progression-free survival (PFS) were 56.5% (95% confidence interval [CI], 49.2-65.0), 14.1% (95% CI, 9.4-21.0), and 196 days (95% CI, 176-233) with CHOP-19; and 56.4% (95% CI, 51.4-61.9), 17% (95% CI, 13.4-21.6), and 209 days (95% CI, 187-224) with CHOP-25. The 1-year, 2-year and median overall survival (OS) were 36.9% (95% CI, 29.7-46.0), 13.5% (95% CI, 8.6-21.1), and 302 days (95% CI, 249-338) with CHOP-19; and 42.8% (95% CI, 37.7-48.7), 15.4% (95% CI, 11.7-20.4), and 321 days (95% CI, 293-357) with CHOP-25. No significant difference in PFS and OS was found between the 2 protocols. Our study confirmed similar outcomes for dogs with PNBCL treated with 1st-line CHOP-19 or CHOP-25. Both protocols therefore could be used as a standard of care in future trials.

Enhancing Lymphoma Diagnosis, Treatment, and Follow-Up Using 18F-FDG PET/CT Imaging: Contribution of Artificial Intelligence and Radiomics Analysis.

Lymphoma, encompassing a wide spectrum of immune system malignancies, presents significant complexities in its early detection, management, and prognosis assessment since it can mimic post-infectious/inflammatory diseases. The heterogeneous nature of lymphoma makes it challenging to definitively pinpoint valuable biomarkers for predicting tumor biology and selecting the most effective treatment strategies. Although molecular imaging modalities, such as positron emission tomography/computed tomography (PET/CT), specifically 18F-FDG PET/CT, hold significant importance in the diagnosis of lymphoma, prognostication, and assessment of treatment response, they still face significant challenges. Over the past few years, radiomics and artificial intelligence (AI) have surfaced as valuable tools for detecting subtle features within medical images that may not be easily discerned by visual assessment. The rapid expansion of AI and its application in medicine/radiomics is opening up new opportunities in the nuclear medicine field. Radiomics and AI capabilities seem to hold promise across various clinical scenarios related to lymphoma. Nevertheless, the need for more extensive prospective trials is evident to substantiate their reliability and standardize their applications. This review aims to provide a comprehensive perspective on the current literature regarding the application of AI and radiomics applied/extracted on/from 18F-FDG PET/CT in the management of lymphoma patients.

Lymphoma in Sub-Saharan Africa: a scoping review of the epidemiology, treatment challenges, and patient pathways.

Improving cancer outcomes in Sub-Saharan Africa (SSA) requires effective implementation of evidence-based strategies. This scoping review maps the evidence on lymphoma epidemiology, treatment challenges, and patient pathways in SSA from 2011 to 2022. A comprehensive three-step search was conducted without language restrictions. Eighty-four publications were included, 83% published after 2017. Southern and Eastern Africa led in output. Most studies were chart reviews (47.6%) and cohort studies (25%). NHL accounted for over 80% of cases, with an age-standardized rate (ASR) reaching 10.9/100,000, while HL had an ASR of 0.4-2.3/100,000. Compared to studies in Europe and US, SSA studies reported lower incidence rates, higher HIV comorbidity, and younger median ages. Diagnosis is often delayed, incomplete and lacks sub-classification with HIV and tuberculosis further complicating care. One-year survival rates are around 50% for NHL and over 75% for HL. Treatment is well-tolerated with an acceptable treatment-related mortality rate. However, outcomes are affected by diagnostic delays, late presentations, and treatment abandonment. Non-clinical aspects of care such as financial constraints negatively impact patient pathways. Addressing diagnostic delays, misdiagnosis, and treatment abandonment is crucial. Strengthening care access, diagnostics, and integrating innovative strategies including a multidisciplinary approach and re-designing efficient clinical diagnostic pathways are vital.

Antibody-Based Therapies for Peripheral T-Cell Lymphoma.

While antibody-based immunotherapeutic strategies have revolutionized the treatment of B-cell lymphomas, progress in T-cell lymphomas has suffered from suboptimal targets, disease heterogeneity, and limited effective treatment options. Nonetheless, recent advances in our understanding of T-cell biology, the identification of novel targets, and the emergence of new therapies provide hope for the future. In this review, we explore four areas of current and evolving antibody-based strategies for the treatment of peripheral T-cell lymphoma (PTCL): monoclonal antibodies (mAbs), bispecific antibodies (BsAs), chimeric antigen receptor T-cell therapy (CAR-T), and antibody-drug conjugates (ADCs). As part of this discussion, we will also include limitations, lessons learned, and potential future directions.

FDA Approval Summary: Polatuzumab Vedotin in the First-Line Treatment of Select Large B-cell Lymphomas.

In April 2023, the U.S. Food and Drug Administration granted regular approval to polatuzumab vedotin-piiq in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (pola+R-CHP) for adult patients who have previously untreated diffuse large B-cell lymphoma, not otherwise specified or high-grade B-cell lymphoma and who have an International Prognostic Index score of 2 or greater. Approval was based on POLARIX, a randomized, double-blinded, placebo-controlled trial evaluating the superiority of substituting vincristine with polatuzumab vedotin in the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen as first-line therapy for patients with large B-cell lymphoma (LBCL). Efficacy was based on investigator-assessed progression-free survival (PFS) in 879 patients who were randomized to receive pola+R-CHP or R-CHOP, followed by two cycles of rituximab alone. PFS was statistically significantly longer with pola+R-CHP with a HR of 0.73 [95% CI: 0.57, 0.95] and log-rank p-value of 0.0177 (two-sided α=0.05). There was no improvement demonstrated in the key secondary endpoints of CR rate at the end of therapy or overall survival (OS). Several issues raised uncertainty about the benefit-risk of polatuzumab vedotin in this curative-intent setting including the modest PFS benefit of pola+R-CHP and lack of OS benefit. The application was therefore presented at an Oncology Drug Advisory Committee. This article summarizes key aspects of the regulatory review, including perspectives on PFS and OS results and other endpoints.

Breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma is a subtype of non-Hodgkin's lymphoma that can occur around the surface of textured breast implants or in patients who have previously had textured breast implants. The condition should be suspected in cases of late-onset breast asymmetry and seroma formation around a breast implant. If the implant and surrounding connective tissue capsule is removed, the prognosis is usually very good. The purpose of this clinical review article is to provide a brief overview of the diagnosis and treatment of breast implant-associated anaplastic large cell lymphoma.

Automatic detection and segmentation of lesions in 18 F-FDG PET/CT imaging of patients with Hodgkin lymphoma using 3D dense U-Net.

The accuracy of automatic tumor segmentation in PET/computed tomography (PET/CT) images is crucial for the effective treatment and monitoring of Hodgkin lymphoma. This study aims to address the challenges faced by certain segmentation algorithms in accurately differentiating lymphoma from normal organ uptakes due to PET image resolution and tumor heterogeneity. Variants of the encoder-decoder architectures are state-of-the-art models for image segmentation. Among these kinds of architectures, U-Net is one of the most famous and predominant for medical image segmentation. In this study, we propose a fully automatic approach for Hodgkin lymphoma segmentation that combines U-Net and DenseNet architectures to reduce network loss for very small lesions, which is trained using the Tversky loss function. The hypothesis is that the fusion of these two deep learning models can improve the accuracy and robustness of Hodgkin lymphoma segmentation. A dataset with 141 samples was used to train our proposed network. Also, to test and evaluate the proposed network, we allocated two separate datasets of 20 samples. We achieved 0.759 as the mean Dice similarity coefficient with a median value of 0.767, and interquartile range (0.647-0.837). A good agreement was observed between the ground truth of test images against the predicted volume with precision and recall scores of 0.798 and 0.763, respectively. This study demonstrates that the integration of U-Net and DenseNet architectures, along with the Tversky loss function, can significantly enhance the accuracy of Hodgkin lymphoma segmentation in PET/CT images compared to similar studies.

Characterization of Clinical Course, Diagnosis, Treatment, and Outcomes of Intravascular Lymphoma with Neurologic Involvement

Characterization of Clinical Course, Diagnosis, Treatment, and Outcomes of Intravascular Lymphoma with Neurologic Involvement

Non-cryopreserved autologous peripheral blood stem cell transplantation for multiple myeloma and lymphoma in countries with limited resources: practice considerations from the Worldwide Network for Blood and Marrow Transplantation.

Autologous peripheral blood stem cell (PBSC) transplantation is a standard treatment of multiple myeloma (MM), Hodgkin lymphoma and various subtypes of non-Hodgkin lymphoma. Cryopreservation of hematopoietic stem cells is standard practice that allows time for delivery of conditioning regimen prior to cell infusion. The aim of this Worldwide Network for Blood & Marrow Transplantation (WBMT) work was to assess existing evidence on non-cryopreserved autologous transplants through a systematic review/meta-analysis, to study feasibility and safety of this approach. We searched PubMed, Web of Science and SCOPUS for studies that utilized non-cryopreserved autologous PBSC transplantation. Identified literature was reviewed for information on mobilization, apheresis, preservation and viability, conditioning regimen, engraftment, response, and survival. Results highlight collective experience from 19 transplant centers (1686 patients), that performed autologous transplants using non-cryopreserved PBSCs. The mean of infused CD34+ was 5.6 × 106/kg. Stem cell viability at transplantation was >90% in MM and >75% in lymphomas, after a storage time of 24-144 h at +4 °C. Mean time-to-neutrophil engraftment was 12 days and 15.3 days for platelets. Pooled proportion estimates of day 100 transplant-related mortality and graft failure were 1% and 0%, respectively. Non-cryopreservation of apheresed autologous PBSCs appears feasible and safe.

7008 Challenges in the Management of Thyroid Lymphoma - Case Report

Abstract Disclosure: F. Toloza Bonilla: None. P. Veeraraghavan: None. R. Lakhotia: None. M. Roschewski: None. N. Nilubol: None. S. Gubbi: None. J. Klubo-Gwiezdzinska: None. Introduction: Primary thyroid lymphoma is an extremely rare thyroid malignancy accounting for less than 5% thyroid malignancies. The management depends on the histological subtype and tumor staging, typically involving chemotherapy alone or combined with radiotherapy. Although, surgical intervention is generally not recommended, given the potential surgical risks and the absence of additional benefits compared to chemoradiation therapy, it is reserved to obtain tissue diagnosis and to treat compressive symptoms. Clinical Case: A 66-year-old Caucasian female presented with dysphagia to solid food and acute neck swelling for a few weeks. History was negative for fever, weight loss or nocturnal diaphoresis. The patient had a history of primary hypertension, pre-diabetes, and Hashimoto’s hypothyroidism. A neck computed tomography (CT) scan showed a thyromegaly (8.3 x 5.8 cm) and bilateral cervical lymphadenopathy. Thyroid ultrasound showed sub centimeter nodules in the right mid-gland and a heterogeneous and irregular left thyroid lobe. TSH was normal (0.87 mcIU/mL [0.27-4.2]). She was treated for suspected subacute thyroiditis with prednisone for two weeks, showing initial clinical improvement, but symptoms recurred after steroids were stopped. Subsequently, a CT neck and fludeoxyglucose F18 (FDG) positron emission tomography (PET) scan demonstrated FDG avid thyroid enlargement with local adenopathy and rightward tracheal deviation. Lymph node, FNA, core biopsies and molecular testing were consistent with stage IIE MYC/BCL6 rearranged diffuse large B-cell lymphoma as she had no bone marrow or central nervous system (CNS) involvement. The patient’s treatments included four cycles of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab with ibrutinib added after the first cycle and intrathecal methotrexate with cycles 3-6, to reduce the risk of CNS involvement. A 6-month post-therapy follow-up showed complete response (CR) on imaging with symptoms resolution. Four months later, she experienced worsening symptoms, including dysphagia with solids and liquids, and hoarseness despite CR to therapy and stable CT imaging. Laryngoscopic evaluation noted left vocal cord paralysis and extrinsic compression of the tracheoesophageal groove. Patient opted for a left hemithyroidectomy, experiencing excellent symptom relief. Surgical pathology showed findings consistent with a necrotic tumor and residual areas of lymphocytic thyroiditis. No active DLBCL was appreciated. The patient remains in remission and continues to be symptoms-free 24 months post-thyroid lymphoma treatment. Conclusion: While thyroidectomy is not typically recommended as the initial treatment for primary thyroid lymphoma, it emerges as a potentially effective option to manage recurrent or persistent compression symptoms following the completion of medical therapy. Presentation: 6/3/2024

Technical comment on: Trottmann M, et al. Real-world expenditures and survival time after CAR-T treatment for large B-cell lymphoma in Switzerland: a retrospective study using insurance claims data.

Technical comment on: Trottmann M, et al. Real-world expenditures and survival time after CAR-T treatment for large B-cell lymphoma in Switzerland: a retrospective study using insurance claims data.

In situ engineering of mRNA-CAR T cells using spleen-targeted ionizable lipid nanoparticles to eliminate cancer cells

Chimeric antigen receptor (CAR) T cell therapy has implemented impressive advances in the treatment of B-cell lymphoma. However, the complex production process of CAR T cells and hindrance of solid tumor penetration remain substantial challenges. Intriguingly, cell-targeting delivery of messenger RNA (mRNA) with ionizable lipid nanoparticles (mRNA-LNPs) is able to efficiently and precisely engineer T cells and other immune cells in vivo to perform their functions. Herein, we harnessed the ionizable LNPs to encapsulate mRNA encoding anti-tyrosinase related protein 1 (TRP1) CAR (CAR-LNPs) for in vivo generation of mRNA-CAR T cells to eliminate melanoma cells. Specifically, the anti-CD3 antibody (aCD3) armed mRNA-LNPs (CD3-mRNA-LNPs) selectively targeted T cells, resulting in the production of functional and therapeutic levels of CAR T cells both ex vivo and in vivo. These CD3-CAR-LNPs engineered CAR T cells were capable of infiltrating into the solid tumor and effectively eliminating melanoma cells with high TRP1 expression, significantly hindering tumor progression. Critically, CD3–7CAR-LNPs containing mRNA encoding both CAR and interleukin-7 (IL-7) generated 7CAR T cells that secreted IL-7, thereby enhancing the activity and proliferation of both CAR T cells and other intratumoral cytotoxic T cells. Alternatively, the employment of anti-programmed cell death protein 1 antibody (aPD-1) protected mRNA-CAR T cells from exhaustion, especially in combination with CD3–7CAR-LNPs, could significantly enhance the antitumor capability of CAR T cells without causing acute cytokine release syndrome (CRS).

B-280 Nmr-based biomaker measurement determines high-dose methotrexate elimination rates in lymphoma and leukemia treatment

Abstract Background The cytotoxic methotrexate (MTX) is used in high doses in lymphoma and acute lymphocytic leukemia (ALL) treatment. A therapeutic plasma dose range is crucial to minimize MTX accumulation and prolonged exposure, which can lead to myelosuppression and other adverse effects. Determining MTX elimination prior to drug administration is difficult, given its non-linear clearance. Here we present a model to predict MTX elimination rates based on metabolite measurement in patients receiving high-dose methotrexate, using nuclear-magnetic resonance (NMR) spectroscopy. Methods A series of 26 residual sera from patients receiving MTX infusions as per treatment protocols for CNS lymphoma (MATRIX protocol, 3.5 g/m2 over four hours) and ALL (GMALL protocol, 1.5 g/m2 over 24 hours) were collected from patients at the University Hospital Regensburg at four timepoints (t0, t24, t42, and t48). Serum was NMR-measured in five replicates. NMR spectra for each sample were characterized and relevant parameters extracted. First order elimination constants were modeled for two MTX dosage regimes (<4 g, ≥4 g) using characterized NMR features from samples measured at t0. Results Metabolomic and lipidomic biomarkers measured at baseline (t0) were able to accurately predict MTX elimination rate constant k, determined by fitting MTX levels at a t24, t42, and t48, using first order c(t)∼c0*e(-kt) kinetic function (>4 g: R2 = 0.475, p-value < 0.05; ≤4 g: R2 = 0.918, p-value < 0.01) (Fig. A). Results were cross-validated with five-time repeated three-fold cross-validation. Performance values are given as means of the folds. Conclusions NMR-measured biomarkers can predict dose-dependent MTX elimination rates in patients receiving high-dose MTX, presenting a novel method to predict MTX clearance, allowing for personalized dose-monitoring and minimization of adverse events. Validation with a larger cohort is required.

Pegylated interferon-α2a in cutaneous T-cell lymphoma - a multicenter retrospective data analysis with 70 patients.

Interferon-alpha is an important therapeutic option for the treatment of the cutaneous T-cell lymphomas (CTCL). Since the approved recombinant interferon-α-2a(IFN-α2a) has no longer been produced sinceJanuary 2020, pegylated interferon-α2a (pegIFN-α2a) can be used as an alternative treatment, even though it is not approved for the treatment of CTCL. The aim of this multicentre study was to generate comprehensive data on the efficacy and tolerability of pegIFN-α2a in the treatment of CTCL. A multicenter retrospective study was conducted with 70 patients with CTCL from twelve German skin centers. In total, 70 patients were included in the study, with 57.2% male and a mean age of 58.8 ±14.9 years. Mycosis fungoides was present in 71.4% of cases and Sézary Syndrome in 28.6%. An overall response rate of 55.2% was observed with pegIFNα-2a therapy. In 50% of cases, therapy was discontinued after 63.6 ±33.5 weeks. The most common reason for discontinuation was adverse events, which occurred in 68.6% of cases and which were classified as severe in 29.2%. Blood count changes, fatigue and liver toxicity occurred most frequently. Our analysis provides comprehensive data on the efficacy and tolerability of pegIFNα-2a therapy in patients with CTCL. In terms of response rates and side effect profile, pegIFNα-2a appears to be comparable to IFN-α2a therapy.

Longitudinal Health-Related Quality of Life Among Patients With High-Risk Pediatric Hodgkin Lymphoma Treated on the Children's Oncology Group AHOD 1331 Study.

PURPOSEThere have been no previous longitudinal assessments of health-related quality of life (HRQoL) during treatment for pediatric Hodgkin lymphoma (HL). The addition of brentuximab vedotin (BV) to a multidrug chemotherapy backbone demonstrated superior efficacy to standard chemotherapy for patients with pediatric high-risk HL in the AHOD 1331 trial. However, the impact on HRQoL is unknown.PATIENTS AND METHODSAfter treatment random assignment, 268 participants older than 11 years were enrolled in a prespecified, longitudinal, patient-reported outcomes substudy. HRQoL was assessed using the seven-item Child Health Ratings Inventories (CHRIs)-Global scale before treatment (T1) and at cycle 2 (T2), cycle 5 (T3), and end of treatment (T4). A clinically meaningful increase in HRQoL was considered 7 points on the CHRIs-Global. Multivariable linear regression estimated associations between demographic/clinical variables and HRQoL at T1. Linear mixed models estimated changes in HRQoL across the treatment arm.RESULTSParticipant characteristics were balanced by treatment arm. Ninety-three percent of participants completed the CHRIs at T1, 92% at T2, 89% at T3, and 77% at T4. At T1, female sex and fever (P < .05) were each associated with worse HRQoL. By T2, participants in the BV arm experienced a statistically and clinically significant improvement in HRQoL (β = 7.3 [95% CI, 3.2 to 11.4]; P ≤ .001), which was greater than the change in the standard arm (difference in change β = 5.1 [95% CI, -0.2 to 10.3]; P = .057). The standard arm did not experience a statistically or clinically significant increase in HRQoL until T4 (β = 9.3 [95% CI, 4.7 to 11.5]; P < .001).CONCLUSIONThese data demonstrate successful collection of serial HRQoL from youth with high-risk pediatric HL and improvement in HRQoL over the course of initial therapy, sooner and to a greater extent in the group receiving the novel agent BV.