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The treatment paradigm for classic Hodgkin lymphoma (CHL) continues to evolve, particularly in light of the incorporation of programmed cell death protein 1 (PD-1) inhibitors into a variety of therapeutic settings. PD-1 inhibitors have demonstrated high efficacy and a favorable toxicity profile when added to a doxorubicin, vinblastine, dacarbazine chemotherapy backbone in patients with untreated CHL. PD-1 inhibitors are also effective treatment options in the relapsed/refractory setting. For patients who are pursuing autologous stem cell transplant (ASCT), pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin has shown marked efficacy and is an effective treatment regimen to administer prior to transplant. For patients who either are not eligible for ASCT or have relapsed after ASCT, pembrolizumab or nivolumab monotherapy have been well studied and demonstrate high efficacy even when patients have been exposed to numerous lines of prior therapy. As data from previous trials continue to mature and new clinical trials are conducted, PD-1 inhibitors will continue to become an integral component for successful management of CHL., (Copyright © 2024 by The American Society of Hematology.)

The CD30-directed antibody-drug conjugate brentuximab vedotin (BV) was FDA approved in 2011 for the treatment of relapsed classic Hodgkin lymphoma (cHL), in 2015 for maintenance after autologous transplantation in high-risk patients, and in 2018 for frontline therapy with doxorubicin, vinblastine, and dacarbazine for advanced stage cHL. Although the role of BV in cHL had been reasonably well-established, it is currently being challenged by the changing landscape of other highly effective novel agents, such as checkpoint inhibitor immunotherapies. In this review, we discuss the evolving role of BV in the management of cHL and ongoing studies attempting to define the optimal usage of this effective agent., (Copyright © 2024 by The American Society of Hematology.)

Background: Early-stage Hodgkin's lymphoma in adults is commonly treated with combined modality treatment of chemotherapy followed by radiotherapy. The role of radiotherapy has been questioned due to potential long-term adverse effects., Objectives: To assess the effects of chemotherapy compared to chemotherapy plus radiotherapy in adults with early-stage Hodgkin's lymphoma., Search Methods: We updated all previous searches for randomised controlled trials (RCTs) on the databases Cochrane Central Register of Controlled Trial, MEDLINE and Embase, in trial registries and in relevant conference proceedings until November 2023., Selection Criteria: We included RCTs comparing chemotherapy alone with chemotherapy plus radiotherapy in adults with early-stage Hodgkin's lymphoma and excluded trials with more than 20% of participants with advanced Hodgkin's lymphoma. We considered immunotherapy in addition to chemotherapy eligible if both were applied similarly in the comparator groups, but did not identify such trials. For our comparisons, we separated RCTs with the same number of chemotherapy cycles in both arms and RCTs with a different number of cycles, when the chemotherapy regimens were the same. We separated RCTs which compared participants with a favourable, mixed or unfavourable risk profile., Data Collection and Analysis: Two review authors independently screened search results, extracted data and assessed the quality of included trials. A third review author resolved discrepancies. We analysed time-to-event outcomes (overall survival, progression-free survival) as hazard ratios (HR) and binary outcomes (adverse events) as risk ratios (RR). We assessed the certainty of evidence using the GRADE approach., Main Results: We included nine comparisons of eight RCTs involving 3840 participants in this updated review. Same number of chemotherapy cycles in both trial arms Favourable disease For overall survival in individuals with favourable Hodgkin's lymphoma, the evidence is uncertain and inconclusive (HR 0.92, 95% confidence interval (CI) 0.11 to 7.92; 2 RCTs, 1245 participants; very low-certainty evidence due to study limitations, inconsistency and imprecision). Additional radiotherapy to chemotherapy is likely to improve progression-free survival (HR 0.36, 95% CI 0.20 to 0.68; 2 RCTs, 1245 participants; moderate-certainty evidence due to study limitations). The evidence was uncertain and inconclusive for second-cancer-related mortality (RR 0.93, 95% CI 0.01 to 74.24; 2 RCTs, 1245 participants; very low-certainty evidence due to study limitations, inconsistency and substantial imprecision) and suggests little to no difference in cardiac disease-related mortality (RR 0.89, 95% CI 0.06 to 14.16; 1 RCT, 667 participants; low-certainty evidence due to substantial imprecision). There were no data on infection-related mortality or infertility. Mixed population For a population of mixed risk profile, the evidence on overall survival is uncertain and inconclusive (HR 0.79, 95% CI 0.13 to 4.80; 2 RCTs, 572 participants; very low-certainty evidence due to study limitations, inconsistency and imprecision). It indicates that additional radiotherapy may lead to an improvement in progression-free survival (HR 0.71, 95% CI 0.43 to 1.17; 2 RCTs, 572 participants; low-certainty evidence due to study limitations and imprecision). The evidence is uncertain and inconclusive for infection-related mortality (RR 1.35, 95% CI 0.17 to 10.87; 2 RCTs, 572 participants) and second-cancer-related mortality (RR 0.52, 95% CI 0.09 to 2.98; 2 RCTs, 572 participants) (both very low-certainty evidence due to study limitations and substantial imprecision), but suggests that additional radiotherapy may increase cardiac disease-related mortality (RR 3.03, 95% CI 0.12 to 73.92; 1 RCT, 420 participants; low-certainty evidence due to substantial imprecision). There were no data on infertility. Unfavourable disease For individuals with unfavourable disease, the evidence on overall survival is uncertain and inconclusive (HR 0.69, 95% CI 0.20 to 2.44; 2 RCTs, 688 participants; very low-certainty evidence due to study limitations and substantial imprecision), but additional radiotherapy probably improves progression-free survival (HR 0.55, 95% CI 0.19 to 1.60; 1 RCT, 651 participants; moderate-certainty evidence due to imprecision). The evidence was uncertain and inconclusive for cardiac disease-related mortality (RR 2.85, 95% CI 0.12 to 65.74; 1 RCT, 37 participants; very low-certainty evidence due to study limitations and substantial imprecision). There were no data on infection-related mortality, second-cancer related mortality or infertility. Different number of chemotherapy cycles in both trial arms Favourable disease The evidence for overall survival in individuals with favourable disease treated with different numbers of chemotherapy cycles in both arms is uncertain and inclusive (HR 0.36, 95% CI 0.04 to 3.38; 1 RCT, 357 participants; very low-certainty evidence due to study limitations and substantial imprecision), yet it suggests a likely improvement in progression-free survival with additional radiotherapy (HR 0.08, 95% CI 0.02 to 0.32; 1 RCT, 357 participants; moderate-certainty evidence due to study limitations). For second-cancer-related mortality, the evidence is uncertain and inconclusive (RR 0.21, 95% CI 0.01 to 4.34; 1 RCT, 465 participants; very low-certainty evidence due to study limitations and substantial imprecision). There were no data on infection-related mortality and infertility and data for cardiac disease-related mortality were not estimable (no events in either group). Unfavourable disease For individuals with an unfavourable risk profile, additional radiotherapy may decrease overall survival slightly (HR 1.66, 95% CI 0.95 to 2.90; 2 RCTs, 698 participants; low-certainty evidence due to study limitations and imprecision), but may slightly improve progression-free survival (HR 0.84, 95% CI 0.53 to 1.33; 2 RCTs, 698 participants; low-certainty evidence due to study limitations and imprecision). The evidence is uncertain and inconclusive for infection-related mortality (RR 6.90, 95% CI 0.36 to 132.34; 1 RCT, 276 participants), second-cancer-related mortality (RR 2.19, 95% CI 0.77 to 6.19; 2 RCTs, 870 participants) and cardiac disease-related mortality (RR 1.60, 95% CI 0.31 to 8.22; 2 RCTs, 870 participants) (all very low-certainty evidence due to study limitations and substantial imprecision). There were no data on infertility., Authors' Conclusions: The chemotherapy regimens in the trials differed and data for regimens commonly used today were limited. Additional radiotherapy may slightly improve progression-free survival. The available data for overall survival and adverse events were of low and very low certainty, and we were unable to draw conclusions about the effects of additional radiotherapy on these outcomes. No studies evaluated infertility. High-quality, longer-term follow-up data are required and data on fertility are needed., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: B-HOLISTIC was a real-world retrospective study of treatment patterns and clinical outcomes in Hodgkin lymphoma (HL) in regions outside Europe and North America. This subgroup analysis reports findings from Saudi Arabia, Türkiye, and South Africa., Materials and Methods: Patients aged ≥18 years and diagnosed with stage IIB-IV classical HL receiving frontline chemotherapy (frontline cHL) and/or with relapsed/refractory HL (RRHL) from January 2010 to December 2013 were assessed. The primary endpoint was progression-free survival (PFS) in patients with RRHL., Results: Overall, 694 patients (RRHL: n=178; frontline cHL: n=653) were enrolled. Among patients with RRHL, >80% received first salvage chemotherapy. The most common first salvage regimens were etoposide, methylprednisolone, cytarabine, and cisplatin in Saudi Arabia (78.3%) and dexamethasone, cytarabine, and cisplatin in Türkiye (36.1%) and South Africa (40%). Median PFS (95% confidence interval [CI]) in the RRHL group was 5.1 (3.0-15.9), 19.7 (7.5-not reached), and 5.2 (1.1-10.1) months in Saudi Arabia, Türkiye, and South Africa, respectively. The 5-year PFS and overall survival (95% CI) rates in patients with RRHL were 33.2% (21.6-45.2) and 78.2% (65.9-86.5) in Saudi Arabia, 42.5% (29.5-54.9) and 79.4% (67.2-87.5) in Türkiye, and 13.1% (4.2-27.0) and 53% (35.5-67.8) in South Africa, respectively., Conclusion: This study showed that the clinical outcomes in Türkiye and Saudi Arabia were generally comparable with those of Western countries during the study period, although Saudi Arabia had lower PFS rates. Conversely, the clinical outcomes in South Africa were suboptimal, emphasizing the need for novel therapies and improved progression to stem cell transplantation. These data may serve as a control group for future studies in these countries and inform clinical decision-making., Competing Interests: Conflict of Interest: David Brittain received honoraria from Takeda Pharmaceuticals, Roche, AbbVie, Merck Sharp and Dohme, Amgen, Hetero, AstraZeneca, and Janssen and serves as a member of advisory committees for Takeda Pharmaceuticals, Hetero, and Janssen. Jaimendra Prithipal Singh received consulting fees from Roche, Janssen, and Novartis and serves as a member of the advisory boards of Janssen, Novartis, and Roche. Lydia Dreosti received honoraria from Janssen, Eli Lilly, Novartis, Roche, and Merck Sharp and Dohme as speaker fees and serves as a member of advisory committees for Roche and Eli Lilly. Mubarak Al-Mansour received honoraria from Roche, Janssen, Bristol Myers Squibb, and AstraZeneca and serves as a member of a board of directors or advisory committee for Takeda Pharmaceuticals. Mohsen Alzahrani received honoraria from Takeda Pharmaceuticals, Kite Pharma, Novartis, and Merck Sharp and Dohme and serves as a member of an advisory committee for Takeda Pharmaceuticals. Sevgi Kalayoğlu Beşışık serves as a member of advisory committees for Novartis, Takeda Pharmaceuticals, Amgen, and Janssen. Güray Saydam received honoraria from Novartis, Alexion, Janssen, Bristol Myers Squibb, and Amgen and serves as a member of an advisory committee for Novartis. Zhongwen Huang is an employee of Takeda Pharmaceuticals and holds shares in the company. Yacob Pinchevsky was an employee of Takeda Pharmaceuticals at the time of the study. Burhan Ferhanoğlu serves as a member of the board of directors or advisory committee for Takeda Pharmaceuticals, Janssen, and Pfizer. Saad Akhtar, Sylvia Rodrigues, Moosa Patel, Dhaya Moodley, Zainab Mohamed, M. Shahzad Rauf, Irfan Maghfoor, and Can Boğa have nothing to disclose., (©Copyright 2024 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House.)

Adolescents and young adults (AYAs) with a history of cancer are at an increased risk for late effects from their cancer treatment and have higher rates of long-term morbidity and mortality compared to their age-matched peers. As a result, this vulnerable population needs attentive follow-up care, end-organ surveillance, and secondary cancer screening; however, a history of cancer can often become buried on a problem list or not addressed at all. This case report illustrates an AYA survivor of classic Hodgkin lymphoma who relocates to a new city and establishes care with a new primary care provider (PCP). The PCP's awareness of a prior cancer diagnosis and the previous treatment regimen is a critical component in providing comprehensive care. In this case, the PCP's first step is to reach out and collaborate with oncology providers to gather an accurate treatment summary and then consult evidence-based guidelines to develop a plan of care. Based on the patient's previous treatment with chemotherapy adriamycin, bleomycin, vinblastine, and dacarbazine, the PCP orders recommended testing, reviews results, and provides subsequent counseling on health promotion and psychosocial wellness. This case illustrates strategies healthcare providers can use to provide coordinated, evidence-based care for AYA cancer survivors., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The ECHELON-1 trial demonstrated the effectiveness of brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine as a frontline treatment regimen in classical Hodgkin lymphoma. However, peripheral neuropathy (PN) is common with this regimen, occurring in up to two-thirds of patients. While standard prescribing information recommends BV dose modification at the onset of grade 2 PN, management strategies for PN are not well-defined. Most commonly, clinicians dose reduce or discontinue BV, vinblastine, or both. We review evidence-based and practical approaches for managing peripheral neuropathy, emphasizing early detection and dose modification., Competing Interests: Declaration of Competing Interest Jeremy Abramson declares support for the present manuscript (no payments made)– Seagen; grants or contracts from any entity – Seagen, Merck, Mustang Bio, Cellectis, Bristol Myers Squibb, Genentech/Roche; consulting fees – Bristol Myers Squibb, AstraZeneca, AbbVie, Genentech/Roche, Kite Pharma/Gilead, Seagen, Interius, BeiGene, Cellectar, Lilly, Incyte, Caribou Biosciences, Takeda, Janssen, Epizyme, Century Therapeutics, MorphoSys, Mustang Bio, Ono Pharma, Kymera; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events – Genmab, Bristol Myers Squibb, AstraZeneca, Regeneron, AbbVie. Robert Stuver declares no conflicts related to this manuscript. Alex Herrera declares grants or contracts from any entity – Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, Karyopharm, Kite Pharma, Gilead Sciences, AstraZeneca, ADC Therapeutics; consulting fees – Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, Karyopharm, ADC Therapeutics, Takeda, Tubulis, Regeneron, Genmab, Pfizer, Caribou Biosciences, Adicet Bio, AbbVie, Allogene. Emily Patterson declares no conflicts related to this manuscript. Yi-Ping Wen declares no conflicts related to this manuscript. Alison Moskowitz declares grants or contracts from any entity – Leukemia Lymphoma Society – Career Development Program, Incyte, Merck, Secura Bio, Bristol Myers Squibb, Syndax, Seagen, Genentech, Kite Pharma, Gilead Sciences, AstraZeneca, ADC Therapeutics; consulting fees – Bristol Myers Squibb, Genentech, Merck, Seagen, AstraZeneca, ADC Therapeutics, Takeda, Genmab, Pfizer, Caribou Biosciences, Adicet Bio, AbbVie, Allogene Therapeutics; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events – Affimed, Bio Ascend, Canadian Heme Conference, Janpix, Physician Education Resource, Academic Medical Education, BP, Great Debates & Updates, Harborside Press, Imbrium Therapeutics, International Symposium on Hodgkin Lymphoma, Kyowa Hakko Pharma, Medscape, Merck Sharp & Bohue, Ahompr, Seagen, Takeda, Tessa, Triangle Insights Group, UpToDate, WebMD; participation on a data safety monitoring board or advisory board – Affimed, Janpix, Seagen, Kyowa Hakko Pharma., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Classical Hodgkin Lymphoma (CHL) is a rare malignant neoplasm of the lymphatic system. While CHL typically responds well to conventional treatments, some cases may experience relapse to other subtypes, with the development of secondary peripheral T-cell lymphoma (PTCL) being relatively uncommon. Herein, we report a rare case of nodal T follicular helper cell lymphomas,nos (nTFHL-NOS) secondary to CHL, accompanied by aberrant CD20 expression and clonal rearrangements of T-cell receptor (TCR) and immunoglobulin (IG). A 74-year-old male, was diagnosed with CHL, leaning toward the mixed cell type, 6 years ago. He received six cycles of the Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) regimen, achieving complete clinical remission. The patient was admitted to our hospital due to the appearance of multiple skin nodules 66 months later. Histopathological analysis revealed nTFHL-NOS, with aberrant CD20 expression and clonal rearrangements of TCR and IG. The patient underwent two cycles of chemotherapy with brentuximab vedotin and the Gemcitabine-Oxaliplatin (G-mox) regimen, resulting in a reduction of the skin lesions to 2 cm × 1 cm. We discuss this rare case and review related literature., (© 2024. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

Purpose: Combined modality treatment with chemotherapy followed by consolidation radiation therapy (RT) provides excellent outcomes for patients with early-stage Hodgkin lymphoma. The international standard of care for consolidation RT, involved-site/involved-node radiation therapy (ISRT/INRT), has never been evaluated in a randomized phase 3 trial against the former standard involved-field radiation therapy (IFRT)., Methods and Materials: In the multicenter phase 3 GHSG (German Hodgkin Study Group) HD17 trial, patients with early-stage unfavorable Hodgkin lymphoma were randomized between the standard Combined modality treatment group and a positron-emission tomography (PET)-guided group. In the standard group, patients received 2 cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) and 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy IFRT. In the experimental group, patients received no further therapy if postchemotherapy PET was negative and 30 Gy GHSG INRT, comparable to and therefore termed here ISRT, if PET was positive. Here, we analyze the interim PET-positive patients in a post hoc analysis, and therefore the randomized comparison of IFRT versus INRT/ISRT., Results: A total of 1100 patients were randomized, of which 311 had a positive PET after chemotherapy. Kaplan-Meier estimates of 4-year progression-free survival were 96.8% (95% CI, 91.6%-98.8%) in the IFRT group and 95.4% (95% CI, 89.9%-97.9%; HR, 1.40; 95% CI, 0.44-4.42) in the ISRT group. The pattern of recurrence analyses indicated that none of the cases of disease progression or recurrence in the ISRT group would have been prevented by the use of IFRT. Acute grade 3/4 toxicities occurred in 8.5% of IFRT patients and 2.6% of ISRT patients (P = .03)., Conclusions: For the first time, consolidation INRT/ISRT was randomly compared with IFRT in a phase 3 trial. Regarding progression-free survival, no advantage of IFRT could be demonstrated. In summary, our data confirm the status of INRT/ISRT as the current standard of care., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Karyomegalic interstitial nephritis (KIN) is a rare renal diagnosis associated with both genetic and medication etiologies. The primary gene associated with KIN is the FAN1 gene which encodes a protein responsible for DNA interstrand repair. Common medication triggers of KIN are chemotherapeutic agents, especially those which disrupt DNA structure such as carboplatin. Despite overlap between these mechanisms, it has not clearly been established if medication usage requires an underlying genetic predisposition for triggering KIN or if medications alone are sufficient. This ambiguous pathogenesis can make it difficult to appropriately assess risk of KIN development when starting patients on one of the known KIN-inducing therapies. Additionally, brentuximab vedotin, an antibody-drug conjugate directed against CD30, has not been previously implicated in KIN development., Case Presentation: We present a 49-year-old woman previously diagnosed with metastatic Hodgkin's lymphoma who was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine, then 3 cycles of ifosfamide, carboplatin, etoposide, all of which were discontinued due to side effects. Following an episode of acute kidney injury, the serum creatinine was 1.09 mg/dL. She then received 2 doses of brentuximab, the serum creatinine rose, and the drug was discontinued. Kidney biopsy done 2 months after brentuximab and 5 months following ifosfamide therapies showed karyomegalic interstitial nephritis. Genetic evaluation showed no FAN1 gene mutations. The patient was started on pembrolizumab; no steroids were given due to concerns about interference with lymphoma immunotherapy. She remains with stable disease and stable chronic kidney disease., Conclusions: This case presents a patient who developed KIN with a progressively rising serum creatinine after ifosfamide, carboplatin and brentuximab treatment. Although ifosfamide and carboplatin have known associations with the development of KIN, this case raises the possibility that brentuximab, which has a different mechanism of action, also may be associated with KIN. Additionally, the genetic findings demonstrate that drug-induced KIN can develop in the absence of FAN1 mutations, a finding not previously reported., Competing Interests: Declarations Ethics approval and consent to participate This case report was reviewed and deemed not to need Institutional Review Board Approval at Cedars Sinai Medical Center. The patient has provided consent for genetic studies. Consent for publication Patient has given written informed consent for all information presented in this manuscript, including personal and clinical details, to be included and to be submitted as written. Competing interests None, (© 2024. The Author(s).)

Background: Routine childhood immunization against varicella-zoster virus has led to a dramatic reduction in the incidence of primary varicella. However, there are rare, yet significant cases reported of reactivated Oka-strain varicella, primarily in immunocompromised hosts., Case Presentation: A 16-year-old female with Hodgkin's lymphoma developed a vesicular rash shortly after completing all chemotherapy treatment. Swabs obtained from the vesicles were positive for varicella-zoster virus. By the time of hospitalization, the patient developed a disseminated rash involving multiple dermatomes. Subsequent polymerase chain reaction confirmed Oka vaccine-strain varicella-zoster virus. The patient had previously received a primary series of immunizations against varicella in 2008 and 2012, with her 2nd dose given 11 years prior to her development of vaccine-strain herpes zoster and 10 years prior to her diagnosis of Hodgkin's lymphoma, respectively. The patient was treated with parenteral acyclovir upon hospitalization and monitored clinically for cutaneous disease progression as well as sequelae. After 8 days of inpatient treatment, her rash had stopped spreading with no new lesions. All earlier lesions had crusted over. No serious sequelae of disease such as pneumonitis, hepatitis, encephalitis, or meningitis occurred, and she made a complete recovery., Conclusions: There are individual and community-wide benefits to childhood immunization against varicella. This case highlights an unusual presentation of disseminated vaccine-strain herpes zoster in an adolescent with secondary immunodeficiency 11 years after completing primary immunization. In addition, this case informs pediatricians of complications that can arise in immunized subjects if they become immunosuppressed years later. The only way to distinguish between wild-type and vaccine-strain herpes zoster was by viral genotyping. Providers should be cognizant of potential vaccine virus reactivation in their differential. Considerations for work-up and management should include infection control and viral resistance in refractory cases., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Written informed consent was obtained from the patient’s legal guardian. Consent for publication Written informed consent was obtained from the patient’s legal guardian for the publication of this case report, including images. The patient also assented to publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

A man in his 30s with a history of refractory classical Hodgkin's lymphoma presented with subacute onset asymmetric sensory disturbance, and severe weakness affecting his right more than left hand. Symptom onset was 18 weeks after commencing brentuximab vedotin (BV) treatment, an anti-CD30 antibody drug-conjugate for relapsed/refractory classical Hodgkin's lymphoma. Symptoms progressed to his lower limbs with distal sensory loss, gait imbalance, bilateral foot drop and mild proximal leg weakness. He was globally areflexic. Neurophysiology revealed a mildly asymmetric, non-length dependent, motor >sensory polyradiculoneuropathy, with mixed axonal and demyelinating features. Extensive laboratory work-up, lumbar puncture and MRI of the brachial plexus, brain, spine and chest were unremarkable. Treatment with plasma exchange, followed by intravenous immunoglobulin, resulted in objective clinical improvement 4 weeks after. BV is a potent antimicrotubule agent, thus well known to cause a length-dependent sensory axonal polyneuropathy. Demyelinating polyneuropathy, with more prominent motor involvement, in association with BV is much rarer., Competing Interests: Competing interests: CO has received a speaker fee on plasma exchange from Terumo BCT. NM, HJH and RA have no conflicts of interest to declare., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the efficacy and safety of brentuximab vedotin (BV) combined with rituximab and attenuated chemotherapy in the treatment of children with classic Hodgkin lymphoma (cHL). Methods: A prospective, non-randomized, risk-assigned study. Clinical data (including age, gender, B symptoms, bulky disease, CD30 and Epstein-Barr virus-encoded RNA(EBER) expression, clinical stage, risk stratification, etc.) of 28 intermediate to high-risk cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2022 to May 2024 were collected. Immuno-targeted combined with attenuated chemotherapy was administered based on risk stratification and early treatment response. The patients were followed up until May 1st, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 28 patients, there were 22 males and 6 females, the age was 12 (5,16) years, 16 cases (57%) presented with bulky disease and 10 cases (36%) with B symptoms. The most common pathological type was nodular sclerosis (14 cases, 50%). There were 7 cases of stage Ⅱ, 14 cases of stage Ⅲ and 7 cases of stage Ⅳ according to the Ann Arbor staging system. There were 5 cases in the intermediate-risk group and 23 cases in the high-risk group. EBER was positive in 20 cases (71%) and negative in 6 cases (21%), and CD30 antigen was expressed in tumor cells of all enrolled children. Treatment duration: 5 cases (18%) received 4 courses of treatment, 21 cases (75%) received 6 courses of treatment, and 2 cases (7%) received 8 courses of treatment, 25 cases (89%) achieved complete metabolism response (CMR) through early assessment after 2 courses of chemotherapy. The CMR rates were 100% in intermediate-risk group and 87% (20/23) in high-risk group, respectively. Four patients (14%) finally received residual field radiotherapy. Toxicities included grade Ⅰ-Ⅱ myelosuppression, early infusion reaction and mild peripheral neuropathy, only one case of grade 3 adverse events was recorded and did not affect sequential treatment. At the end of treatment and 3 months of follow-up, the levels of IgA, IgG and IgM were all decreased compared with the baseline before chemotherapy, and the total B cell count began to be lower than the level before chemotherapy at the early stage of treatment (after 2 courses). The total B cell count monitored during treatment was 50 (0, 101)×10 6 /L and was 12 (0, 25)×10 6 /L at the end of treatment. The follow-up time was 6 (3, 13) months, all 28 children had event-free survival and all achieved complete remission. At 6 and 9 months of follow-up, IgA, IgG, IgM and total B cell counts returned to pre-chemotherapy baseline levels, respectively. Conclusion: BV combined with rituximab attenuated chemotherapy has demonstrated efficacy and a tolerable safety profile in the treatment of cHL in children, and significantly reduce radiation rate.

Background: Prolonged fever of more than a year duration can be a symptom of underlying malignancy. This article appreciates the need for diligent history taking and carefully performed clinical examination, which is fundamental to reaching an initial diagnosis., Case: We report the case of a middle-aged male who presented to us with a fever of more than a year duration. The patient's residence was located in a remote area where the nearby tertiary care center was almost 250 km away. He was empirically treated with antibiotics without any success by local physicians. After more than a year, he reported to us and was diagnosed with Hodgkin lymphoma with a characteristic Pel-Ebstein pattern of fever missed earlier by the local physicians. His fever resolved within 5 days of chemotherapy, and he achieved complete remission., Conclusion: Meticulous history-taking and clinical examination are essential for reaching a clinical diagnosis. Malignant causes should be considered in the differentials of prolonged fever., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

In elderly patients with high-risk classic Hodgkin lymphoma (c-HL), we evaluated the impact of a new modality treatment without bleomycin, that is, liposomal doxorubicin (NPLD)-based regimen plus consolidation radiotherapy of residual nodal masses (RNMs), on overall survival (OS) and progression free survival (PFS). In this retrospective study (2013-2023) conducted in tertiary hospitals in the bay of Naples (Italy), 50 older adults (median age, 69 years; range, 60-89) with advanced stage c-HL received frontline treatment with MVD ± irradiation. MVD consisted of 25 mg/m 2 of NPLD along with standard Vinblastine and Dacarbazine for a total of 6 cycles (twelve iv administrations, every 2 weeks) followed by radiation of RNMs with size ≥ 2.5 cm at computed tomography. Patients underwent MVD with a median dose intensity of 92%. At 2-deoxy-2[F-18] fluoro-D-glucose positron emission tomography (FDG-PET), 90% of patients (45/50 patients; one failed to perform final FDG-PET due to early death) reached complete responses. Altogether, 17 patients (34%) received consolidation radiotherapy of RNMs with Deauville score ≥ 3. At 5-year median follow-up, the OS and PFS of the entire population were 87.5% (95% confidence interval [CI], 78.7-97.4) and 81.6% (95% CI, 71.4-93.2), respectively. Eleven patients (22%) experienced grade ≥ 3 adverse events, and 4 of them required hospitalization. Our data suggest that in older adults with high-risk c-HL NPLD-driven strategy (without bleomycin) plus consolidation radiotherapy (if needed) may be a promising up-front option, to test in phase II clinical trials for improving survival incidence., (© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

Study Question: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters?, Summary Answer: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility., What Is Known Already: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. The present study aims to assess the (gonadotoxic) impact of this treatment protocol on semen parameters and reproductive hormones in boys aged ≤18 years., Study Design, Size, Duration: This international, prospective, multi-centre cohort study was an add-on study to the randomized phase-3 EuroNet-PHL-C2 trial, where the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) was compared to intensified OEPA-DECOPDAC-21 chemotherapy (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide). Patients were recruited between January 2017 and September 2021., Participants/materials, Setting, Methods: Eligibility criteria included male patients, diagnosed with classical HL before or at the age of 18 years, and treated according to the EuroNet-PHL-C2 protocol in any of the 18 participating sites in the Netherlands, Germany, Belgium, Czech Republic, and Austria. Sperm parameters (sperm concentration, progressive motility, sperm volume, and calculated total motile sperm count) were assessed at diagnosis and 2 years after diagnosis in (post)pubertal boys. Laboratory measurements (serum follicle-stimulating hormone (FSH) and inhibin B) were performed in samples drawn at diagnosis, during treatment (2-3 times), and at 2 years post-diagnosis, and (age-adjusted) analyses were conducted separately for pre-pubertal and (post)pubertal boys. Outcomes were compared between the treatment levels (TL1, TL2, and TL3) and consolidation treatment schemes (COPDAC-28 and DECOPDAC-21)., Main Results and the Role of Chance: In total, 101 boys were included in the present analysis: 73 were (post)pubertal (median age 15.4 years, (IQR 14.4; 16.6), 10 TL1, 29 TL2, 34 TL3, 62% of TL2/3 patients received COPDAC-28) and 28 boys were pre-pubertal (median age 9.6 years (IQR 6.6; 11.4), 4 TL1, 7 TL2, 17 TL3, 38% of TL2/3 patients received COPDAC-28). The study included six boys who had received pelvic radiotherapy; none were irradiated in the inguinal or testicular area. At diagnosis, 48 (post)pubertal boys delivered semen for cryopreservation; 19 (40%) semen samples were oligospermic and 4 (8%) were azoospermic. Low sperm concentration (<15 mil/ml) appeared to be related to the HL disease itself, with a higher prevalence in boys who presented with B symptoms (76% vs 26%, aOR 2.3 (95% CI 1.0; 3.8), P = 0.001) compared to those without such symptoms. At 2 -years post-diagnosis, 31 boys provided semen samples for analysis, of whom 12 (39%) boys had oligozoospermia and 4 (13%) had azoospermia, while 22 boys (71%) had low total motile sperm counts (TMSC) (<20 mil). Specifically, the eight boys in the TL3 group treated with DECOPDAC-21 consolidation had low sperm counts and low progressive motility after 2 years (i.e. median sperm count 1.4 mil/ml (IQR <0.1; 5.3), n = 7 (88%), low sperm concentration, low median progressive motility 16.5% (IQR 0.0; 51.2), respectively). Age-adjusted serum FSH levels were significantly raised and inhibin B levels (and inhibin B:FSH ratios) were decreased during chemotherapy in (post)pubertal boys, with subsequent normalization in 80% (for FSH) and 60% (for inhibin B) of boys after 2 years. Only 4 out of the 14 (post)pubertal boys (29%) with low sperm concentrations after 2 years had elevated FSH (>7.6 IU/l), while 7 (50%) had low inhibin B levels (<100 ng/l). In pre-pubertal boys, reproductive hormones were low overall and remained relatively stable during chemotherapy., Limitations, Reasons for Caution: The present analyses included sperm and laboratory measurements up to 2 years post-diagnosis. Long-term reproductive outcomes and potential recovery of spermatogenesis remain unknown, while recovery was reported up to 5- or even 10-year post-chemotherapy in previous studies.Boys who were pre-pubertal at diagnosis were still too young and/or physically not able to deliver semen after 2 years and we could not assess a potential difference in gonadotoxicity according to pubertal state at the time of treatment. Overall, the statistical power of the analyses on sperm concentration and quality after 2 years was limited., Wider Implications of the Findings: Results of the semen analyses conducted among the 31 boys who had provided a semen sample at 2 years post-treatment were generally poor. However, additional long-term and adequately powered data are crucial to assess the potential recovery and clinical impact on fertility. The participating boys will be invited to deliver a semen sample after 5 years. Until these data become available, benefits of intensified chemotherapy in cHL treatment to reduce radiotherapy and lower risk for development of secondary tumours should be carefully weighed against potentially increased risk of other late effects, such as diminished fertility due to the increased chemotherapy burden. Boys with newly diagnosed cHL should be encouraged to deliver sperm for cryopreservation whenever possible. However, patients and clinicians should also realize that the overall state of disease and inflammatory milieu of cHL can negatively affect sperm quality and thereby reduce chance of successful fertility preservation. Furthermore, the measurement of FSH and inhibin B appears to be of low value in predicting low sperm quality at two years from cHL treatment., Study Funding/competing Interest(s): This study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M.-K., D.K., W.H.W., D.H., MC, A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors declare no potential conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Hodgkin lymphoma (HL) occuring during pregnancy is a rare condition, and management relies on sparse literature. The specificity of pregnancy requires the clinician to take into account the clinical emergency, the stage of the lymphoma, the trimester of pregnancy, and the patient's choices. The main objective is twofold: to limit the risk of toxicity and adverse events for both mother and fetus, without reducing the chances of a successful outcome. Current literature data suggest that the use of ABVD-type polychemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine) is associated with obstetrical events and long-term fetal toxicity. We report here the results of a homogeneous management considering wait-and-see, vinblastine monotherapy and ABVD polychemotherapy options. The outcomes in terms of obstetrical complications, response rate, and overall survival (100 %) reinforce the idea that strategies that do not involve the use of multidrug therapy are possible and are associated with very good results., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Classic Hodgkin lymphoma (HL) is rare disease, with an incidence of approximately 85,000 patients globally per year and a predilection for adolescents and young adults (ages 15-39). Since the introduction of combination chemotherapy in the 1960's and radiation dating back to the early 1900's, therapeutic options and by extension, clinical outcomes have improved dramatically with 5-year overall survival (OS) approaching 90% today. [1](#ref-0001) Advances in understanding HL biology have additionally facilitated development of targeted agents and immunotherapy which have further improved short and long-term outcomes. Despite continued improvements in up-front and salvage therapy, long-term survivors of HL experience several treatment-associated late toxicities, thus, along with efforts to improve therapeutic efficacy, efforts to reduce late effects remain a high-priority in the field., (© 2023 John Wiley & Sons Ltd.)

Abstract: DNA methyltransferase inhibitor decitabine plus anti-programmed cell death 1 (DP) therapy was effective in relapsed/refractory classic Hodgkin lymphoma (cHL). However, a subset of patients experienced primary resistance or relapse/progression after DP therapy. In this study, we evaluated the efficacy and safety of a triplet regimen consisting of the histone deacetylase inhibitor chidamide, decitabine, and anti-PD-1 camrelizumab (CDP) in 52 patients who previously received DP therapy. CDP treatment was well tolerated and resulted in an objective response rate of 94% (95% confidence interval [CI], 84-99), with 50% (95% CI, 36-64) of patients achieving complete response (CR). Notably, all patients who were recalcitrant to previous DP treatment exhibited therapeutic responses after CDP therapy, although their CR rate was lower than patients responsive to prior DP. Overall, the median progression-free survival was 29.4 months. Through single-cell RNA sequencing of pretreatment and on-treatment cHL tumor biopsy samples, we observed the heterogeneity of rare malignant Hodgkin Reed/Sternberg (HRS)-like cells. The classical CD30+ HRS-like cells interacted with abundant immunosuppressive IL21+CD4+ T helper cells, forming a positive feedback loop that supported their survival. While the CD30- HRS-like cell population showed potential resistance to anti-PD-1 immunotherapy. CDP treatment promoted the activation of diverse tumor-reactive CD8+ T cells and suppressed the proliferation of IL21+CD4+ T cells by inhibiting STAT1/3 signaling, thereby alleviating their immunosuppressive effects. These findings provide insights into the cHL microenvironment that contributes to anti-PD-1 resistance and highlight the therapeutic effectiveness of dual epi-immunotherapy in overcoming immunotherapy resistance. This trial was registered at www.clinicaltrials.gov as #NCT04233294., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Incorporating brentuximab vedotin into the treatment of advanced-stage classic Hodgkin's lymphoma improves outcomes in adult and pediatric patients. However, brentuximab vedotin increases the toxic effects of treatment in adults, more than half of pediatric patients who receive the drug undergo consolidative radiation, and relapse remains a challenge. Programmed death 1 blockade is effective in Hodgkin's lymphoma, including in preliminary studies involving previously untreated patients., Methods: We conducted a phase 3, multicenter, open-label, randomized trial involving patients at least 12 years of age with stage III or IV newly diagnosed Hodgkin's lymphoma. Patients were randomly assigned to receive brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (BV+AVD) or nivolumab with doxorubicin, vinblastine, and dacarbazine (N+AVD). Prespecified patients could receive radiation therapy directed to residual metabolically active lesions. The primary end point was progression-free survival, defined as the time from randomization to the first observation of progressive disease or death from any cause., Results: Of 994 patients who underwent randomization, 970 were included in the intention-to-treat population for efficacy analyses. At the second planned interim analysis, with a median follow-up of 12.1 months, the threshold for efficacy was crossed, indicating that N+AVD significantly improved progression-free survival as compared with BV+AVD (hazard ratio for disease progression or death, 0.48; 99% confidence interval [CI], 0.27 to 0.87; two-sided P = 0.001). Owing to the short follow-up time, we repeated the analysis with longer follow-up; with a median follow-up of 2.1 years (range, 0 to 4.2 years), the 2-year progression-free survival was 92% (95% CI, 89 to 94) with N+AVD, as compared with 83% (95% CI, 79 to 86) with BV+AVD (hazard ratio for disease progression or death, 0.45; 95% CI, 0.30 to 0.65). Overall, 7 patients received radiation therapy. Immune-related adverse events were infrequent with nivolumab; brentuximab vedotin was associated with more treatment discontinuation., Conclusions: N+AVD resulted in longer progression-free survival than BV+AVD in adolescents and adults with stage III or IV advanced-stage classic Hodgkin's lymphoma and had a better side-effect profile. (Funded by the National Cancer Institute of the National Institutes of Health and others; S1826 ClinicalTrials.gov number, NCT03907488.)., (Copyright © 2024 Massachusetts Medical Society.)

Purpose: Response assessment of classical Hodgkin lymphoma (cHL) with positron emission tomography-computerized tomography (PET-CT) is standard of care in well-resourced settings but unavailable in most African countries. We aimed to investigate correlations between changes in PET-CT findings at interim analysis with changes in blood test results in pediatric patients with cHL in 17 South African centers., Methods: Changes in ferritin, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), albumin, total white cell count (TWC), absolute lymphocyte count (ALC), and absolute eosinophil count were compared with PET-CT Deauville scores (DS) after two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine in 84 pediatric patients with cHL. DS 1-3 denoted rapid early response (RER) while DS 4-5 denoted slow early response (SER). Missing values were imputed using the k-nearest neighbor algorithm. Baseline and follow-up blood test values were combined into a single difference variable. Data were split into training and testing sets for analysis using Python scikit-learn 1.2.2 with logistic regression, random forests, naïve Bayes, and support vector machine classifiers., Results: Random forest analysis achieved the best validated test accuracy of 73% when predicting RER or SER from blood samples. When applied to the full data set, the optimal model had a predictive accuracy of 80% and a receiver operating characteristic AUC of 89%. The most predictive variable was the differences in ALC, contributing 21% to the model. Differences in ferritin, LDH, and TWC contributed 15%-16%. Differences in ESR, hemoglobin, and albumin contributed 11%-12%., Conclusion: Changes in low-cost, widely available blood tests may predict chemosensitivity for pediatric cHL without access to PET-CT, identifying patients who may not require radiotherapy. Changes in these nonspecific blood tests should be assessed in combination with clinical findings and available imaging to avoid undertreatment.

Introduction: Treatment of cancer has been improved with the discovery of biological drugs that act as immune checkpoint inhibitors. In 2017, FDA designated pembrolizumab, an immune checkpoint inhibitor employed in immunotherapy, as the first tissue-agnostic cancer treatment., Objectives: To review pembrolizumab's use in oncology, gather and examine the latest discoveries regarding the effectiveness of pembrolizumab in cancer treatment., Methodology: A literature review was conducted through PubMed(Medline) from January 2015 to December 2023 using "pembrolizumab", "cancer" and "treatment" as search terms., Results: Pembrolizumab demonstrated effectiveness as primary treatment for metastatic nonsmall cell lung cancer, unresectable esophageal cancer, head and neck squamous cell carcinoma and alternative treatment for notable triple-negative breast cancer, biliary, colorectal, endometrial, renal cell, cervical carcinoma, and high microsatellite instability or mismatch repair deficiencies tumors. Pediatric applications include treatment for refractory Hodgkin lymphoma., Conclusion: Evolving research on pembrolizumab allows a deeper clinical understanding, despite challenges as variable patient responses. Pembrolizumab has emerged as a pivotal breakthrough in cancer treatment, improving patient outcomes and safety., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Background: FDG PET is required for the staging and response evaluation of pediatric Hodgkin lymphoma. This study aimed to evaluate the outcomes of pediatric patients with Hodgkin's lymphoma based on interim PET CT assessments of early response following second-cycle chemotherapy using the Deauville score (DS). It also determines whether DS-3 is providing an adequate or inadequate response., Methods: We conducted a retrospective cohort study including 504 pediatric patients with classic Hodgkin lymphoma who were treated with chemotherapy based on the Euro-Net protocol at the Children Cancer Hospital Egypt from March 2019 till the end of October 2022., Results: Patients with adequate response DS 1/2 and DS 3 showed nearly the same 3-year event-free survival (EFS) of 91.9% and 91.5%, respectively, compared with those patients with inadequate response DS 4/5, who showed an EFS of 80.4% ( P =0.001). Patients with a DS 3 at interim PET evaluation were considered negative as DS 1/2. Patients of DS 3 group who did not receive radiotherapy had a much worse 3-year EFS by the existence of positive B symptoms, an ESR>30, or an advanced stage. Radiation therapy did not improve the 3-year EFS in patients with an inadequate response (DS4/5) and poor prognostic characteristics. They still need more advanced treatment., Conclusion: DS 1/2 and DS 3 had about the same 3-year EFS, which is better than the 3-year EFS of patients with DS 4/5. Therefore, we can classify DS 3 as having negative FDG PET CT uptake., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: BV is an antibody-drug conjugate directed against CD30 and is safe and effective in relapsed/refractory (R/R) Hodgkin lymphoma (HL). Most patients with r/r cHL respond well to BV monotherapy; however, the large of majority of them eventually progress on this drug, and BV-resistant HL remains an unmet need. Preclinical data suggest that BV resistance is mediated at least in part by increased drug efflux associated with increased expression of multidrug resistance pump 1 (MDR1) while CD30 expression appears to be preserved in BV resistant cell lines and patient samples. We conducted a phase 1 study evaluating BV + cyclosporine (CsA) in BV-refractory HL and previous reported results in the dose finding cohort. Here we report the final results from the phase 1 study., Methods: This was a phase I trial of BV + CsA in patients with r/r HL with dose-finding and dose escalation cohorts. Eligibility criteria included age ≥ 18 years with r/r HL after at least 1 prior line of therapy. Treatment consisted of 1.8 mg/kg BV intravenously on day 1 and CsA 5 to 7.5 mg/kg PO twice daily on days 1 to 5; cycles were 21 days long. Patients in the expansion cohort had to have cHL refractory to BV. The primary objectives were to evaluate safety and tolerability and to determine MTD of BV + CsA; the secondary objective was to determine efficacy of this combination., Results: 29 patients were enrolled onto the study, 14 in the dose finding cohort and 15 in the dose expansion BV refractory cohort. Study accrual was terminated before target accrual due to unacceptable toxicity. 62% of patients were male, and the median age was 36 years (range: 20-69). The median number of prior therapies was 5 (range: 3-12); all patients had prior BV, and 93% had PD-1 directed therapy, and 93% were BV-refractory. Of 22 evaluable patients, CR rate was 27% and ORR 64%; median DOR 4.9 months. Treatment-related deaths occurred in 3 patients, and another patient died during cycle 1 due to cardiac arrest deemed unlikely related to be protocol therapy. All grade GI toxicity was seen in 90% of patients (G3+ in 24%); other common adverse events were nausea (90%), hypertension (90%), nausea (90%), hypertension (90%), anemia (86%), fatigue (76%), neutropenia (76%), leukopenia (76%), hypomagnesemia (76%), anorexia (66%), and hyponatremia (66%)., Discussion: BV + CsA demonstrated modest activity in BV-refractory r/r HL; however, toxicity is substantial., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although checkpoint molecules like CTLA-4 and PD1 have been described several years ago, checkpoint inhibitors such as nivolumab (an anti-PD-1 antibody) have only recently been used to treat classic Hodgkin lymphoma (cHL). Several studies have shown convincing therapeutic effects of nivolumab in cHL. However, the mechanism of action of nivolumab in cHL is not fully understood. The aim of this study was to monitor changes in cell motility and cell contacts after administration of nivolumab to an in vitro model of cHL as well as to native hyperplastic lymphoid tissue and native human tissue from cHL. In both tissue and in vitro, CD4+, CD8+, CD30+ and CD20+ cell velocities were unchanged after nivolumab incubation. In contrast, in primary cHL tissue, the duration of cell contacts between CD4+ T cells and Hodgkin-Reed-Sternberg cells was significantly increased after 5 hours of nivolumab treatment, and the number of contacts with HRS cells was also slightly increased for CD4+ T cells (not significant), suggesting that CD4+ T cells in particular contribute to the cytotoxicity observed as a result of nivolumab therapy. There was no change in the duration of cell contacts in the hyperplastic lymphoid tissue after nivolumab incubation. In conclusion, we show here for the first time by imaging of native lymphoma tissue an enhanced interaction of CD4+ T cells and Hodgkin-Reed-Sternberg cells in cHL after nivolumab administration.

The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has spurred important treatment changes over recent decades. This study aimed to examine mortality among young HL patients treated with contemporary strategies, including historical data comparison. This nationwide study included 1348 HL patients, diagnosed in 1995-2015 and aged 15-40 at diagnosis. Among the patients, 66.5% had Ann Arbor stage I-II and 33.5% had stage III-IV disease. With a median follow-up of 14.76 years, 139 deaths occurred, yielding a 5-year overall survival of 94.6%. Older age, advanced disease, earlier treatment periods and extensive regimens were associated with higher overall mortality risk. The cumulative risk of HL-related death showed an initial sharp rise, with a plateau at 5.3% 10-year post-diagnosis. Deaths due to cardiovascular or pulmonary diseases and second cancers initially had minimal risk, gradually reaching 1.2% and 2.0% at the 20-year mark respectively. HL cases had a 7.5-fold higher mortality hazard than the background population. This study suggests that contemporary HL treatment still poses excess mortality risk, but recent changes have notably reduced overall and cause-specific mortality compared to earlier eras. Balancing treatment efficacy and toxicity remains crucial, but our findings highlight improved outcomes with modern treatment approaches., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

We demonstrated that dose-densified and dose-intensified ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; ABVD DD-DI ) was safe and effective. Here, we present a post hoc long-term analysis of the 82 patients enrolled in the original study. The median observation time was 175 months (IQR 159-197). At 15 years, progression-free and overall survival rates were 81.2% (95% CI, 69.9%-88.7%) and 92.7% (95% CI, 82.6%-97.0%), respectively. Four patients with multiple cardiovascular risk factors experienced delayed G3 cardiac events. The cumulative incidence of second malignancies at 20 years was 6.1%. Fertility and childbearing potential were unaffected. Data support an ongoing benefit for ABVD DD-DI without uneven late toxicities., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

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.

This single-arm confirmatory study (JCOG1305) aimed to evaluate the utility of interim positron emission tomography (iPET)-guided therapy for newly diagnosed advanced-stage classic Hodgkin lymphoma (cHL). Patients aged 16-60 years with cHL received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and then underwent an iPET scan (PET2), which was centrally reviewed using a five-point Deauville scale. PET2-negative patients continued an additional four cycles of ABVD, whereas PET2-positive patients switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP). The co-primary endpoints were 2-year progression-free survival (PFS) among all eligible and PET2-positive patients. Ninety-three patients were enrolled between January 2016 and December 2019. One patient was ineligible because of a diagnostic error. The median age of the 92 eligible patients was 35 (interquartile range, 28-48) years. Forty (43%) patients had stage III disease, and 43 (47%) had stage IV disease. The remaining nine (10%) patients had stage IIB disease with risk factors. Nineteen PET2-positive (21%) patients received eBEACOPP, 18 completed six cycles of eBEACOPP, 73 PET2-negative (79%) patients continued ABVD, and 70 completed an additional four cycles of ABVD. With a median follow-up period of 41.1 months, the 2-year PFS of 92 eligible patients and 19 PET2-positive patients were 84.8% (80% confidence interval [CI], 79.2-88.9) and 84.2% (80% CI, 69.7-92.1), respectively. Both primary endpoints were met at the prespecified threshold. This study demonstrates that iPET-guided therapy is a useful treatment option for younger patients with newly diagnosed advanced-stage cHL. Registration number: jRCTs031180218., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Immune checkpoint inhibitors have transformed the future management of classic Hodgkin lymphoma (CHL) in the frontline and salvage settings. Both nivolumab and pembrolizumab have high efficacy in CHL allowing for reduction of chemotherapy and possibly the use of radiotherapy based on short-term follow-up. In this review article, we highlight recent trials enrolling patients with relapse and refractory classic Hodgkin lymphoma receiving monotherapy with PD-1 inhibitors as well as PD-1 and chemotherapy regimens. We also highlight frontline trials utilizing PD-1 inhibitors with chemotherapy with or without radiotherapy. Collectively, the role for radiotherapy in the frontline or salvage setting will become more defined with long-term follow-up of completed studies and results generated from future studies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A significant unmet need remains for patients with Hodgkin lymphoma (HL) who fail to respond to first-line treatment or experience an early relapse. Tinostamustine, a novel alkylating deacetylase inhibitor, inhibits tumor cell growth and slows disease progression in models of hematological malignancies and solid tumors. This was a Phase I, multicenter, open-label, two-stage trial investigating the safety and efficacy of tinostamustine in patients ≥ 18 years with relapsed/refractory (R/R) hematological malignancies, including HL. Stage 1 involved dose-escalation to determine the maximum tolerated dose (MTD) of tinostamustine, optimal infusion time and recommended Phase II dose (RP2D). Stage 2 confirmed the safety and efficacy of the RP2D in expansion cohorts of selected R/R hematological malignancies. Ten patients with heavily pre-treated HL entered dose-escalation, with nine patients experiencing treatment-emergent adverse events (TEAEs) considered to be related to study treatment-primarily hematological toxicities. MTD was 100 mg/m 2 tinostamustine over 60 min and signals of efficacy were observed for patients with HL. In Stage 2, all 20 patients with HL experienced ≥ 1 TEAE, which were principally hematological or gastrointestinal. There were no tinostamustine-related deaths in either stage of the study. Overall response rate in Stage 2 was 37% (2 complete responses, 5 partial responses; 95% confidence interval [CI]: 16%, 62%) and median progression-free survival 3.8 months (95% CI: 2.2-9.4 months). Tinostamustine is a promising new therapeutic approach for the treatment of patients with R/R classical HL with limited options. This study demonstrates a predictable and manageable safety profile with signals of efficacy. Trial Registration: ClinicalTrials.gov identifier: NCT02576496., (© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

Abstract: We present a rare and never-before-reported case of paraneoplastic proliferative myositis that was incidentally detected in a 42-year-old man who had been receiving systemic cytotoxic chemotherapy for classic Hodgkin lymphoma. We highlight his 18 F-FDG PET/CT findings and its utility in helping to diagnose this condition, avoiding unnecessary surgical resection and the added costs associated with it., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Immune checkpoint inhibitors (ICI) are promising therapeutic agents for relapsed or refractory classical Hodgkin's lymphoma (RRcHL). This retrospective study evaluated patients with RRcHL registered in the clinical research program Tohoku-Hematology-Forum-26, between 2016 and 2020, and treated with ICI in 14 centers in Northeast Japan. We analyzed the usage, efficacy, and safety of ICI therapy (ICIT). Among a total of 27 patients with RRcHL, 21 and nine were treated with nivolumab and/or pembrolizumab, respectively. The best response was complete response (CR), partial response (PR), stable disease (SD), and progressive disease in 11 (40.8%), seven (25.9%), eight (29.6%), and one (3.7%) patient, respectively. In all patients undergoing ICIT, the 2-year progression-free survival and 2-year overall survival (OS) were 48.6% and 87.4%, respectively. The 2-year OS for patients with CR, PR, and SD were 100%, 68.6%, and 87.5%, respectively. A total of 36 events of immune-related adverse events (irAEs) or immune-related like adverse events (irlAEs) were observed in 19 of the 27 patients (70.4%). Two thirds of these irAEs or irlAEs were grade 1-2 and controllable. During the observation period, ICIT was discontinued in 22 of 27 (81.4%) patients due to CR, inadequate response, irAE and patient circumstances in five (22.7%), seven (31.8%), eight (36.4%) and two patients (9.1%), respectively. Therapy-related mortality-associated irAE were observed in only one patient during ICIT. These results suggest that ICIT for RRcHL is effective and safe in real-world settings. The optimal timing of induction and duration of ICIT remains to be established.

Although antibody-drug conjugate (ADC) or immune checkpoint inhibitors (ICIs) alone fosters hope for the treatment of cancer, the effect of single drug treatment is limited and the safety profile of ADC and ICI therapy remains unclear. This meta-analysis aimed to examine the efficacy and safety of the combination of ADC and ICI therapy. This study type is a systematic review and meta-analysis. Literature retrieval was carried out through PubMed, Embase, Cochrane from inception to Jun. 5, 2024. Then, after data extraction, overall response rate (ORR) and adverse effects (AEs) were used to study its efficiency and safety. Publication bias was also calculated through Funnel plot, Begg's Test and Egger's test. Heterogeneity was investigated through subgroup and sensitivity analysis. The research protocol was registered with the PROSPERO (CRD42023375601). A total of 12 eligible clinical studies with 584 patients were included. The pooled ORR was 58% (95%CI 46%, 70%). Subgroup analysis showed an ORR of 77% (95%CI 63%, 91%) in classical Hodgkin lymphoma (cHL) and an ORR of 73% (95%CI 56%, 90%) in non-Hodgkin lymphoma (NHL). The most common AEs was peripheral neuropathy (38.0%). Meanwhile, AEs on skin (13.1-20.0%) and digestive system (9.0-36.0%) was hard be overlooked. ADC + ICI therapy may be recommended in cancer treatment, especially in cHL and NHL. However, strategies to manage toxicities warranted further exploration., (© 2024. The Author(s).)

Hodgkin's lymphoma (HL)-associated vanishing bile duct syndrome (VBDS) is a paraneoplastic phenomenon leading to cholestasis, end-stage liver failure and potentially death, due to cholestatic liver dysfunction typically precluding the commencement of curative intent chemotherapy. A female in her 20s presented with pruritus, jaundice and cholestatic hepatitis on laboratory tests, confirmed as VBDS on liver biopsy. CT of the chest demonstrated a mediastinal mass and widespread cervical lymphadenopathy. The patient received 30.6 Gy in 17 fractions to the involved sites of disease which led to a marked improvement in liver function, allowing curative intent chemotherapy to be initiated. The patient achieved complete metabolic response and at the most recent follow-up she had no signs of recurrent disease and near-normal liver function tests. This demonstrates that tumour-directed radiotherapy can be used as a potential bridge to curative chemotherapy in early stage HL-associated VBDS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Brentuximab vedotin and PD-1 inhibitors have improved outcomes for classic Hodgkin lymphoma (cHL), but better therapies are needed for patients who relapse after these agents. Based on an improved understanding of cHL biology, there is a robust pipeline of novel therapies in development. In this review, we highlight emerging immunotherapeutic agents and combinations for cHL., Areas Covered: We review clinical trials of novel PD-1/PD-L1 inhibitors beyond FDA-approved agents, checkpoint inhibitors targeting CTLA-4, LAG-3, TIM-3, TIGIT, and CD47/SIRPα, PD-1 inhibitor combinations with immunomodulatory agents and epigenetic modifying therapies, antibody-drug conjugates, bispecific antibodies, and cellular therapies including anti-CD30 CAR-T and allogeneic NK cell therapy. We review the key safety and efficacy data from published phase 1-2 studies and highlight trials in progress, including the first phase 3 trial for PD-1 inhibitor-refractory cHL., Expert Opinion: Many novel immunotherapies hold great promise in cHL. Rational combinations with existing agents and next-generation antibody and CAR-T constructs may improve response rates and durability. Identifying biomarkers of response to these immunotherapies and using more sensitive tools to assess response, such as circulating tumor DNA, may further inform treatment decisions and enable a precision medicine approach in the future.

Objective: Evaluate the clinical features in people with Hodgkin's lymphoma living with HIV (HIV-HL) during the combination ART (cART) era., Design: Systematic review and meta-analysis., Methods: The study was conducted in accordance with the recommendations of 2020 PRISMA and MOOSE statements. The protocol was prospectively registered through the PROSPERO (CRD42021289520). Manuscripts published until July 2023 were systematically searched in the PubMed, EMBASE, Cochrane Library, and Web of Science databases, with no language and year of publication restriction. Meta-analysis was performed to estimate a pooled proportion of each outcome using a random-effect analysis. Quality assessment was performed by using New-Castle Ottawa scale. Certainty of evidence was graded using the GRADE., Results: Sixteen cohorts, representing 3.882 HIV-HL patients, were included in this review. Our findings indicate that HIV-HL patients showed a 2-year overall survival (OS) of 92% (95% CI 0.87, 0.95). However, the 5-year overall survival decreased to 79% (95% CI 0.74, 0.83), with a high certainty of evidence according to GRADE. Additionally, the 5-year progression-free survival declined to 79% and complete remission rate increased to 81%. Our meta-analysis indicates an increase for B symptoms (80%, 95% CI 0.75, 0.84) and extranodal involvement in bone marrow (43%, 95% CI 0.30, 0.47) among HIV-HL patients., Conclusion: The HIV-HL patients showed a 2-year OS of 92%. However, the 5-year OS decreased to 79%. The reported main cause of mortality among HIV-HL patients was progression of HL. Our systematic review and meta-analysis suggest that cART is associated with improved short-term survival of HIV-HL patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Patients with advanced-stage Hodgkin lymphoma treated with ABVD who have a positive interim FDG-PET (iPET) have a poor prognosis. Escalation to BEACOPP has been shown to improve progression-free survival (PFS). However, randomized trials are lacking to determine the best strategy for intensification. We report on A-AVD escalation treatment outcomes for 15 iPET-positive patients post-ABVD. Overall response and complete response rates were 80% and 60%, respectively. Four patients underwent salvage therapy followed by autologous stem cell transplantation. At a median 17-month follow-up, all patients are alive, 87% in complete remission, and 1-year PFS was 57.8%. For patients ineligible for BEACOPP due to age, comorbidities, or preference, A-AVD escalation may be a viable alternative., (© 2024 John Wiley & Sons Ltd.)

Purpose of Review: In this review, we analyzed the different therapy options in patients with advanced Hodgkin lymphoma (HL)., Recent Findings: The treatment of advanced HL has greatly evolved during the last decade even still based on polychemotherapy. Mature data established that the better strategies require Positron emission tomography (PET)-driven treatments which allow to optimize the balance between disease control and both immediate and late treatment adverse effects, leading to cure most patients while minimizing the risk of toxicity. Indeed, PET-driven deescalated strategies offer the better treatment option. The recent incorporation of targeted therapies, anti-CD30 or anti-programmed cell death protein 1 (PD1) in combination with chemotherapy should quickly change the game and be a step forward to still decrease the risk of treatment toxicity and improve the cure rate., Summary: The standard of care for advanced HL remains currently PET-driven chemotherapy and should rapidly evolve with the addition of targeted therapy combined with chemotherapy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hodgkin Lymphoma (HL) is often curable with ABVD therapy and improving outcomes is a main goal of ongoing research. Bleomycin-associated pneumonitis (BAPT) is a potentially life-threatening complication that necessitates bleomycin discontinuation. We conducted this study on a homogenous cohort of advanced stage HL treated only with ABVD for frontline therapy to assess if bleomycin discontinuation increases the risk of lymphoma progression. After the exclusion of patients who received radiotherapy or other drugs, 106 and 28 patients in the six-cycle ABVD and BAPT groups respectively had similar survival curves for progression and death with a 49-month median follow-up. PFS rates were also very similar at two and four years from diagnosis with 2-year PFS rates of 83.9% and 82.1% (RR = 1.1 95%CI = 0.45-2.2). Outcome comparisons were also similar between the two groups when stratified according to early response assessment with PET/CT. Patients who discontinued bleomycin due to toxicity did not experience an increased risk of progression compared to patients who completed six ABVD cycles.

Purpose of Review: We aim to summarize the current knowledge on the management of early-stage classical Hodgkin lymphoma, with a focus on conventional strategies, incorporation of immunotherapies and exploration of novel prognostic markers., Recent Findings: Long-term data on combined modalities (associating chemotherapy and radiotherapy) still supports their benefit in terms of progression free survival compared to chemotherapy alone in both early favourable and early unfavourable interim PET-negative classical Hodgkin Lymphoma. Novel agents, such as Brentuximab Vedotin and checkpoints inhibitors show promising and impressive results when added to first-line treatment. Various strategies have been used, mainly in phase 2 non randomized clinical trials. Interim PET-scan has limited prognostic value and its role in regimens incorporating immunotherapies is yet unknown. Other prognosis markers emerge, such as metabolic tumour volume and circulating tumour DNA. By reflecting tumour burden pretreatment and minimal residual disease on treatment, they might be useful tools guiding treatment decisions., Summary: Novel immunotherapy agents are likely to change the landscape in front-line management of classical early-stage Hodgkin lymphoma by combined modality treatment. Despite encouraging recent data, proof of their efficacy and safety on the longer term are still needed. Treatment decisions might be guided by new promising prognosis markers but their use in clinical practice is still to be determined., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Historically, salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (HDT/ASCT) was the mainstay approach for relapsed or refractory classic HL. The emergence of novel agents for HL, such as brentuximab vedotin and programmed death-1 (PD-1) blockade has revolutionized therapeutic strategies, yielding excellent results. This review aims to provide a comprehensive overview of new salvage therapies and offer insights into forthcoming therapeutic options., Recent Findings: The incorporation of brentuximab vedotin and PD-1 blockade into salvage therapy before HDT/ASCT has led to markedly improved outcomes. Notably, PD-1 based salvage studies yield posttransplant 2-year progression-free survival rates approaching 90%, marking a significant advancement in the treatment of Hodgkin lymphoma (HL). Studies are beginning to explore nontransplant treatment approaches following front-line treatment failure and may identify certain risk groups eligible for these strategies., Summary: The landscape of HL treatment is rapidly evolving, leading to significant changes in the standard of care. Novel agents are now administered earlier in the disease course, resulting in higher cure rates. The focus of treatment is shifting towards achieving cure with minimal toxicity, reducing exposure to various agents, and advancing research in optimizing treatment sequencing and patient selection for less intensive therapies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Hodgkin lymphoma (HL) occurs at two age peaks around 25 and 60 years of age. Due to varying fitness and co-morbidities older patients are a heterogeneous group that has relatively poor treatment outcomes. The evolving therapeutic landscape for older HL is summarized herein., Recent Findings: Due to lack of data from larger trials and approval of novel drugs, first-line treatment of limited-stage HL (i.e. early-stage favourable and unfavourable) remains largely A(B)VD and radiotherapy based. For patients with advanced-stage HL, the anti-CD30 antibody-drug conjugate brentuximab vedotin is approved in combination with AVD chemotherapy (BV-AVD). Due to toxicities such as febrile neutropenia or polyneuropathy and lack of improvement in progression-free and overall survival in the older subgroup, fully concomitant BV-AVD is however not used widely. More recently, promising early data was reported with the combination of nivolumab and AVD (N-AVD) in patients >60 years with advanced-stage HL. Second-line treatment depends on fitness and might include high-dose chemotherapy and autologous stem-cell transplantation for selected patients. For unfit or multiply relapsed patients, anti-PD1 antibodies are the preferred treatment option., Summary: The increasing number of older HL patients constitutes a therapeutic challenge despite recent advances and the increased usage of targeted agents., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The authors Lanke and Relander describe a patient with classical Hodgkin lymphoma (cHL) stage IIA, who had pain at alcohol consumption as the only symptom at diagnosis. The patient was treated with 4 cycles of ABVD chemotherapy and proton therapy 29.75 Gy (RBE). Apart from FDG-PET/CT the course of the disease was followed with serum-TARC. The case illustrates the value of knowing also rare symptoms at the general practice, the usefulness of TARC as a tumour marker in cHL, and the use of proton therapy in order to further reduce late radiotherapy side effects.

A woman in her 20s with no medical history was diagnosed with bulky stage II classic Hodgkin's lymphoma after an 8-week history of shortness of breath, cough and lethargy. A regimen of doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) was commenced with six cycles planned. During the first cycle, the patient was profoundly hypertensive. She then suffered two self-terminating tonic-clonic seizures.Examination and investigations diagnosed posterior reversible encephalopathy syndrome (PRES), which resolved completely in 11 days with strict blood pressure control and withholding chemotherapy. Treatment was further complicated by anthracycline-induced cardiomyopathy, requiring a switch in regimen to gemcitabine BVD.The patient made a full recovery from neurology and cardiology perspectives and completed six cycles of chemotherapy, achieving a complete metabolic response by the tumour. We illustrate the case, describe differential diagnoses and management of PRES, its association with chemotherapy and the successful chemotherapy rechallenge., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: The overall- and progression-free survival rates of Hodgkin's lymphoma patients have improved. Our goal was to examine the changes in our treatment results and their causes depending on the daily diagnostic and therapeutic practice. Materials and Methods: We analysed data of 776 classical Hodgkin lymphoma patients treated between 1980 and 2019. Patient data were investigated in ten-year periods (first period: 1980-1989, second period: 1990-1999, third period: 2000-2009, and fourth period: 2010-2019). Results: Radiotherapy alone as a first-line treatment was used progressively less often, and in the 4th period it was no longer used before or without chemotherapy. The use of combined chemo- and radiotherapy decreased in the last period, and the number of those patients who received only chemotherapy increased significantly. The 10-year overall survival improved significantly from 1990 to 1999 compared to 2010 to 2019 (74.9% vs. 86.9%). About 30% of patients relapsed after or were refractory to first-line therapy in each period. The incidence of relapse in the last period did not increase after two years, but there was no significant difference between the periods. Conclusions: Overall survival rates of HL patients have improved significantly in recent decades, which is due to improved diagnostic methods and modern therapies. Progression-free survival is unchanged; one-third of patients relapse or are refractory to first-line treatment within the first two years. Early recognition of R/R patients, the early application of newer and already available innovative therapies, and the finding of additional new and effective therapies are of particular importance.

Objective: To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin's lymphoma (R/R cHL). Methods: Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment. Conclusion: Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin's lymphoma in children.

Introduction: The current treatment regimens for Hodgkin's lymphoma (HL) are associated with high incidences of adverse events., Purpose: This study aimed to compare the efficacy and safety of doxorubicin + bleomycin + vincristine + dacarbazine (ABVD) and standard bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (BEACOPP) chemotherapy in the treatment of advanced stage HL., Methods: This multicenter, randomized, parallel, open, positive control noninferiority trial was conducted from 2016 to 2019 and comprised 93 subjects who were randomized in a 1:1 ratio between the treatment (BEACOPP; n = 44) and control (ABVD; n = 49) groups., Results: The primary efficacy endpoint of this trial was the objective response rate (ORR) after eight cycles of chemotherapy, which was 100.00% (36/36) in the treatment group and 95.74% (45/49) in the control group. The incidence of adverse reactions was 100% in both groups. Significant differences (P < 0.05) in the incidences of grade 3 (39/44 [88.64%] vs. 23/49 [46.94%]) and grade 4 (27/44 [61.36%] vs. 8/49 [16.94%]) adverse events were observed between the treatment and control groups, respectively. However, most of these reactions were manageable, with no serious consequences, and were reversible after discontinuation of the treatment., Conclusion: Both regimens had a similar ORR and were associated with a high number of adverse events. The ABVD regimen was better tolerated and safer than the standard BEACOPP regimen. This study indicates that the standard BEACOPP regimen may be considered as a treatment option for patients with advanced HL., (Copyright © 2024 Copyright: © 2024 Journal of Cancer Research and Therapeutics.)

The optimal treatment of classic Hodgkin Lymphoma (cHL) requires an individualized approach, with therapy guided by pretreatment clinical risk stratification and interim response assessment with positron emission tomography (PET). The overall goal is to achieve high cure rates while minimizing acute toxicity and late therapy-related effects. Interim PET-adapted strategies (iPET) were initially developed with traditional chemotherapy, reducing intensity after interim complete response and escalating treatment for patients with iPET+ disease. Recently, novel agents including brentuximab vedotin and the checkpoint inhibitor immunotherapies (CPIs) pembrolizumab and nivolumab have been adopted into the front-line treatment of cHL, and PET-adapted approaches may be relevant for these drugs as well. In this review we discuss response-adapted strategies utilizing novel agents, consider challenges including indeterminate radiographic findings with CPIs, and address emerging techniques for response assessment including new PET-based imaging metrics and the role of circulating tumor DNA., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.S.M. reports no potential conflicts of interest. R.H.A. reports research funding from Genentech/Roche, Gilead, Merck, Millennium, Pharmacyclics, Regeneron, BeiGene, and Seagen Inc; and has served as a consultant for Autolus, Genentech/Roche, Gilead, and ADCT., (Copyright © 2024 Elsevier Inc. All rights reserved.)