ABVD Chemotherapy Research Articles

Fifteen-Year Experience of a Single Institution: Outcomes for Early-Stage Hodgkins Lymphoma Comparing Chemotherapy Alone Versus Combined Modality Therapy

Doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy is the current standard treatment for early-stage Hodgkins lymphoma (HL). The use of consolidative radiation therapy (RT) in addition to chemotherapy may lead to better survival rates but is controversial because of concerns about long-term toxicity. The aim of this study is to compare outcomes of patients receiving ABVD chemotherapy alone (CTX alone) versus ABVD with consolidative RT (CMT). A single-institution, retrospective review of patients with HL diagnosed from 2000 to 2014 was conducted. Patients were identified from the National Cancer Database. Inclusion criteria included patients aged ≥18 years, with stage I or II HL, who received ABVD with a complete response with/without CMT. Consolidative RT must have been started within 90 days of completing chemotherapy. Institutional review board approval was obtained. Follow-up details and treatment responses were collected from medical record reviews. Standard statistical analysis and Kaplan-Meier curves were used to estimate relapse-free survival (RFS). One hundred and 8 patients with early-stage HL were identified. The median age at diagnosis was 31 years (range, 19-72). Most patients were female (63%) and Caucasian (65%). stage II HL was present in 89%of patients, 89% had an Eastern Cooperative Oncology Group score of 0 or 1, 35% had B symptoms, and 9% had extranodal involvement. A total of 52.8% received CMT (n = 57) and 47.2% received CTX alone (n = 51). The CMT group had fewer cycles of chemotherapy compared to the CTX-alone group (mean cycles, 5.2 vs 5.7, P = 0.045). Twenty-four relapse events occurred in the CTX-alone group, while no relapse events occurred in the CMT group. RFS at 10 years was significantly improved in the CMT group (100%) compared to CTX alone (47.4%, P < .0001; HR = .03, P < .001). ABVD with consolidative RT was associated with improved RFS. Further studies of toxicity comparisons, advanced stages, and nonfavorable HL are warranted.

Real-Life Data, a Retrospective Report from Romania Hodgkin’s Lymphoma Registry - Single Center Experience

Background. Hodgkin’s Lymphoma is a type of cancer originating from the lymphatic system, characterized by Reed-Sternberg cells. It is essential due to its distinct clinical presentation, early age at diagnosis, favorable prognosis with early detection and treatment, and the ongoing need for research to optimize therapeutic strategies and improve patient outcomes. Aims: This study evaluates demographic data and clinical features, staging, and treatment options of newly diagnosed Hodgkin’s Lymphoma patients in the biggest Hematology Center in Bucharest, Romania “Fundeni” Clinical Institute Study design: Retrospective study Methods: Demographic data, histopathological and clinical features, treatment modalities, and treatment responses were systematically extracted from hospital records and integrated into the National Hodgkin’s Lymphoma Registry under the auspices of the Romanian Hematology Association. Key dates, including initial diagnosis, remission, relapse, last follow-up, and death, were meticulously documented to facilitate comprehensive survival analysis. Results. We analyzed data from a cohort of Hodgkin Lymphoma patients, comprising both male and female individuals, with a median age of 35. The predominant histological subtype was nodular sclerosis, and the most common stage at diagnosis was stage II. The ABVD chemotherapy regimen (doxorubicin, bleomycin, vinblastine, dacarbazine) was the most frequently administered treatment in the first-line setting. Five-year survival rates were significantly higher in patients diagnosed at an early stage and those with favorable prognostic factors, showing improved overall and relapse-free survival rates. Prognosis factors impacting outcomes included the presence of B-symptoms, serum albumin levels, Eastern Cooperative Oncology Group (ECOG), and LDH levels. Conclusion. The analysis of Hodgkin's Lymphoma data from the Romanian National Registry highlights the critical necessity for the enhancement of diagnostic infrastructure, the promotion of equitable access to advanced treatments, and active engagement in international clinical trials. Addressing these imperative issues through targeted healthcare reforms has the potential to significantly ameliorate patient outcomes and synchronize Romania's management of Hodgkin's Lymphoma with global benchmarks.

Response-Based Approach for Pediatric Hodgkin Lymphoma in Nations with Restricted Resources.

Background: Hodgkin lymphoma (HL) management varies throughout developing nations. This observational study aims to present the results of children having HL who received various combinations of chemotherapy treatment. The response-based method was used regardless of the risk classification. Materials and Methods: We recruited patients≤ 18 years of age diagnosed with HL in an Iraqi cancer center between January 2014 and December 2021. By stratifying patients, three risk categories were identified. Every patient initially received two cycles of ABVD as induction chemotherapy. Following induction chemotherapy, patients showing a full radiological response continued on ABVD chemotherapy for 4-6 cycles without receiving radiotherapy. Patients showing a modest initial response received three additional courses of COPDac next to the third cycle of ABVD, followed by radiotherapy. Results: This study included fifty-nine patients with a median age of 7 years. Stage III patients accounted for 33.9% (n=20), then stage II (32.2%). B symptoms were present in 25 patients. Eleven children had initial splenic involvement. Fifty-two individuals (n = 19; 32.2%) had bulky disease. Mixed cellularity was the most prevalent histology (n=44). The median duration of follow-up was 2.7 years. EFS was 78% ±10%, and survival was 92% at 5-year estimation. Bulky disease was the only factor with a substantial unfavorable impact on the result. Conclusion: Response-based approach is a valuable strategy in nations with limited resources to prevent long-term sequelae from unnecessary radiotherapy.

Hodgkin Lymphoma in Children: A 16-year Experience at the Children's Welfare Teaching Hospital of Baghdad, Iraq.

Childhood Hodgkin lymphoma (HL) is an eminently curable disease. Good outcomes can be achieved even in resource-limited settings, and the focus is increasingly on limiting long-term toxicity. Contemporary treatment incorporates a risk-stratified, response-adapted approach using multiagent chemotherapy with/without low-dose radiotherapy. Many developing countries continue to use ABVD-based regimens due to limited acute toxicity, cost, and ease of delivery. We herein report the outcomes of childhood HL diagnosed and treated in an Iraqi single centre over 16 years. Children ≤14 years old with biopsy-proven HL were enrolled. Most patients received ABVD chemotherapy or COPP/ABV when Dacarbazine was unavailable. Radiotherapy was not available. Three hundred-three children were consecutively newly diagnosed with HL; 284 were considered eligible for the retrospective analysis (treatment refusals 9; deaths before therapy 5; initially diagnosed of non-Hodgkin lymphoma 5). ABVD scheme was administered to 184 children (65%), COPP/ABV to 83 (29%), and other schemes to the remaining 17 patients. Complete response (CR) was achieved in 277 (98%); 4 (1.4%) showed disease progression, and 1 had stable disease. Four patients in CR abandoned therapy and were in CR at the time of analysis, 2 died from infection. Relapse occurred in 42 patients (15%). The 15-year OS and EFS are 89.7% and 70.3%, respectively. In this single Centre, over 16 years, almost 90% of children suffering from HL survive, despite the numerous limitations in diagnostic procedures, shortage of chemotherapy, no radiotherapy facilities, absence of effective second-line treatments, and finally, therapy abandonment for social and financial reasons.

Abstract 3802: Integrating multiplex-staining and multiplex-DIA: Profiling the tumor microenvironment spatial proteome for precision cancer research

Abstract Our innovative dual-dimensional multiplexing approach ushers in a new era of spatial proteomic exploration. Multiplex-staining deepens understanding of tumor-stroma interactions. Our robust dimethyl labeling-based multiplex-DIA workflow enhances throughput and proteome depth in the Deep Visual Proteomics (DVP) technology. Now, our audacious integration of multiplex-staining with multiplex-DIA holds the promise of pushing the boundaries of spatial proteome profiling. This innovation combines the power of mass spectrometry (MS) with clinical viability in 1) requiring just one FFPE section for spatial proteome analysis at the resolution of individual cell types; 2) ingeniously transmuting MS revelations into a clinically feasible staining strategy. A force in personalized oncology, our innovation unravels the intricate dynamics of the cancer ecosystem while ensuring direct clinical relevance. We conducted multiplex immunofluorescent staining on human cancers using the MACSima platform, followed by cellular phenotyping and automated single-cell laser microdissection. Subsequently, we loaded dimethyl-labelled 3-plex tryptic peptides onto Evotips and performed LC-MS analysis using the Evosep One coupled to timsTOF SCP. Pre- and post-22-plex staining proteome analysis confirmed no significant protein loss, validating microdissection compatibility and excellent recovery. The key findings include: 1) profiling of 21 distinct cell types/subtypes in human tonsil cancer tissues, resulting in the identification of 4941 protein groups from a cellular volume of 110,859 µm3, equivalent to approximately 55 cells; 2) observation of a loss of CD45RA/RO expression in tumor-infiltrating cytotoxic T cells, contributing to a reduction in MET and PDGF signaling activity within tumor cells; 3) the presence of abundant cytotoxic T cells, B cells, and plasma cells, coupled with a reduction in tumor cell proliferation, indicative of a hot tumor microenvironment. Proteome analysis revealed enhanced immune cell mobility and interactions with tumor cells. Moreover, our workflow facilitated the identification of potential diagnostic markers for mycosis fungoides, a marker-lacking skin lymphoma, where we achieved the identification of 2964 significant proteins out of a total of 6009. In addition, a rare lymphoma case study not only guided ABVD chemotherapy and suggested IL4 inhibition to address chemoresistance but also identified CDK, MCM, and PSMA/B/C/D/E inhibitors as promising candidates for targeted therapy. The integration of multiplex-staining and multiplex-DIA represents a significant stride in advancing personalized diagnostics and therapeutic strategies. Citation Format: Xiang Zheng, Andreas Mund, Matthias Mann. Integrating multiplex-staining and multiplex-DIA: Profiling the tumor microenvironment spatial proteome for precision cancer research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3802.

Evaluation of a Prognostic 23-Gene Expression Panel in a Set of 390 Multiethnic Hodgkin Lymphoma Patients

Classic Hodgkin lymphoma (CHL) is a curable lymphoma with unique epidemiological features, including rare neoplastic cells, and an adolescent/young adult age (AYA) incidence peak higher in females, correlated with socioeconomic status. We previously reported that RNA expression measured in formalin-fixed paraffin-embedded (FFPE) tissues using a panel of 23 immune response genes was associated with 5-year overall survival (OS) in predominantly White/European advanced staged CHL patients treated with ABVD chemotherapy (Scott et al., 2013). Here, we conducted a study to evaluate if the 23-gene expression panel predicted 5-year OS in a real-world set of FFPE tumor tissue from racially/ethnically diverse populations in the U.S. and Mexico from the Multi- Ethnic Study of Hodgkin Lymphoma (MESH). Methods: We collected tumor blocks from 891 patients from 9 hospitals and 2 Residual Tissue Repositories in the U.S. and Mexico. Demographic and clinical data, including survival by month, age at diagnosis, birth year, race/ethnicity, sex, histology were abstracted. Patients were diagnosed from 1978 to 2018. CHL diagnoses and histological subtypes were validated by histopathology review. RNA was extracted and NanoString gene expression profiling was performed using 250-gene codeset including the published 23-gene expression (GE) panel (Scott et. al., 2013). 390 cases passed QC after applying a modified normalization protocol (Chan et.al., 2017). The multiethnic risk index was derived from a linear equation of the log 2 GE in MESH multiplied by the established regression coefficients (Scott et al., 2013). Next, we examined a dichotomized score using a cut-off value at the 75 th percentile. Both were tested for association with 5-year OS using a Cox proportional hazards model using R software 4.3.0 version adjusting for age as a continuous and categorical variable (15-39 and 40+ years), type of hospital that provided the samples, sex, EBV tumor status (assigned using EBER2), race/ethnicity, and histology. The 5-year OS was computed by right-censoring any patient that survived longer than 5 years. Proportionality assumptions were tested (using an alpha level of 0.05). Stratified models by categorical age and race/ethnicity were adjusted for patient demographical variables and effect heterogeneity was examined using a t-test. Result: The analytic set comprised 47% females and 44% Hispanic, 24% White, 20% Black, 9% Asian, and 3% Pacific Islander/Native Hawaiians. 62% were 15-39 years and 32% 40+ years at diagnosis. The multivariate analysis, excluding age, indicated an association between the risk index and 5-year OS (HR =1.41 (1.08, 1.93), p=0.01). However, including age attenuated the association (HR=1.18 (0.89, 1.57), p=0.25). When stratified by age categories, the continuous risk index was associated with 5-year OS only in the older age group: 15-39 years (HR = 0.89 (0.54, 1.47), p=0.65), and &amp;gt;40 years (HR = 1.47 (1.08, 2.01), p=0.02), indicating effect heterogeneity by age groups (p=0.09). We did not observe significant effect heterogeneity by EBV status (p=0.6), race/ethnicity (p=0.72), nor sex (p=0.33). When the dichotomized score was examined, the model was attenuated after adjusting for age, but stratification analysis showed an association in the older adults (HR= 2.8 (1.42, 5.51), p&amp;lt;0.01) with significant effect heterogeneity across age (p=0.02) (Figure 1). Evaluating the association between individual genes and OS, we found effect heterogeneity by age; two genes from the 23-gene panel indicated protective effects in the AYA but hazardous in older adults: B2M (p effect heterogeneity' =0.048) and APOL6 (p'=0.059). Individual genes with heterogeneity of association across race/ethnicity included RNF144B (p' =0.0021) with increased hazards in Whites compared to Blacks, whereas WDR83 (p'=0.018), PRF1 (p'=0.0018), LYZ (p'=0.0028) had higher hazards in Blacks compared to Whites, and RAPGEF2 (p'=0.036) had higher hazards in Hispanics compared to Whites. Conclusion: The risk index and dichotomized score derived from the previously developed 23-gene panel was significantly associated with OS among &amp;gt;40 year age group, with evidence of age effect heterogeneity. We detected 2 genes with an association that varied by age, and five across race/ethnicity, suggesting the importance of including diverse racial/ethnic and age groups in CHL patient populations when developing predictive models.

Fibrous dysplasia mimicking skeletal involvement in Lymphoma.

We present the case of a 19-year-old male with nodular sclerosing classical Hodgkin lymphoma, who had an incidental finding of fibrous dysplasia of the bone. This caused 18-F-fluorodeoxyglucose (18-F-FDG) avidity on positron emission tomography-computed tomography (PET-CT) scan leading to incorrect initial staging. This patient presented with a 4-month history of enlarging cervical lymph nodes, without B symptoms. He had no prior medical history. His initial diagnostic 18-F-FDG PET-CT demonstrated moderately avid left cervical and superior mediastinal lymphadenopathy and two partially sclerotic, partially lytic bone lesions. These were moderately avid, one in the proximal right humerus (SUV 6.1) and the second in the posterior distal humerus (SUV 8.1). There was no other avid lymphadenopathy (see Figure 1). He had a magnetic resonance imaging (MRI) scan and an orthopaedic opinion was sought; the lesions were felt likely to be skeletal involvement of his Hodgkin lymphoma. Therefore, his staging was 4A, with an international prognostic score of 2, and treatment was commenced following a RATHL approach starting with ABVD chemotherapy. The interim PET-CT scan following cycle 2 of ABVD demonstrated a complete metabolic response within the cervical and mediastinal lymphadenopathy, but persistent avidity within the right humeral shaft lesions which were essentially unchanged in size with a mild reduction in 18-F-FDG avidity (see Figure 2). He did report some aching in the right arm. This discrepant radiological response prompted further investigation. The bone lesions were evaluated with a CT and MRI scan, and his case was discussed again with the orthopaedic team who at that point felt the radiological appearances were suggestive of fibrous dysplasia. He had a biopsy of the bone lesion and histological examination confirmed the diagnosis of fibrous dysplasia with no evidence of Hodgkin lymphoma or other primary bone malignancy. The patient's staging was therefore amended to stage 2A early favourable (ESR 4 mm/h at diagnosis), and treatment was changed to combined modality chemo-radiotherapy. He had already completed 2 cycles of ABVD and so proceeded to receive 20 Gy in 10 fractions of consolidation radiotherapy. His end-of-treatment PET-CT scan is awaited but clinically he remains in complete remission. He will require surveillance imaging of the bony lesions. Fibrous dysplasia of the bone (FD) is an uncommon genetic disorder causing benign fibroosseous bone lesions. It is diagnosed predominantly in children and young adults. It has a wide spectrum of presentations but is often asymptomatic and can be found incidentally. Malignant transformation can rarely occur. Radiological features can vary from classical ground glass lesions to cystic or sclerotic lesions. FD lesions can show a large variability in 18-F-FDG uptake on PET-CT, and avidity in FD may change over time. There are several other case reports of FD mimicking skeletal involvement in lymphoma. In conclusion, discrepant responses to treatment should be further investigated. Careful interpretation of 18-F-FDG avid bone lesions is required to avoid misdiagnosis or overtreatment. FD should be considered within the differential diagnosis, especially in younger patients. Orla Gildea: conception, literature review and writing—original draft preparation Claire Burney: supervision and writing—review and editing Julian Kabala: resources, visualisation The authors declare no conflict of interest. Self. N/A. Uploaded. N/A. Not applicable to this article as no new data were created or analysed.

Revisiting the predictive role of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography on treatment outcome in early-stage favorable Hodgkin lymphoma.

In the present manuscript Gallamini et al. comment the results of three large, phase III, randomized clinical trials in early-stage favorable Hodgkin Lymphoma (HL), aimed at exploring the non-inferiority of ABVD chemotherapy alone compared to combined-modality treatment with ABVD and Involved Field/Node Radiotherapy (INRT). The authors also report the preliminary results of risk-stratification in the first 60 enrolled patients in the phase 2, prospective, international study RAFTING: RAdiotherapy Free Treatment IN Good-prognosis early-stage HL (National Trial Identifier 04866654). In this trial patients are stratified, before treatment onset, according to the risk of therapy failure in a single patient basis, taking into account non only the results of interim and End-of-Therapy PET, but also the value of new metrics extracted from the baseline PET/CT such as the Large Nodal Mass (LNM) and Total Metabolic Tumor Volume (TMTV). Treatment intensity, consisting in ABVD chemotherapy, INRT and Nivolumab maintenance, is modulated on the presence/absence of the above factors, in a personalized-medicine approach. The most frequently detected factors driving treatment intensity were LNM and TMTV, while the results of interim and end-of-treatment PET were also determinant, albeit in a lower percentage of cases.

ABVD for Hodgkin Lymphoma in Malawi; Excellent Outcomes but with Persistent Clinical Disparities Compared to High-Income Countries: A Prospective Cohort Study

BACKGROUND: ABVD is a well-established curative-intent therapy for Hodgkin lymphoma (HL) but, to our knowledge, little has been published about therapy or outcomes in sub-Saharan Africa (SSA) where supportive care is more limited, infectious milieu is different, and in our case, radiation therapy was not available. We report mature data from one of the first prospective HL cohorts treated under real-world conditions in SSA. METHODS: Patients ≥15 years with newly diagnosed HL were enrolled in Malawi from Jul 2013 to Dec 2021 and followed for five years if remain in remission; patients not yet achieveing five years or with relapse were censored May 2022. All participants had diagnosis confirmed by immunohistochemistry during telepathology conference between the team in Malawi and UNC Chapel Hill. Two patients were excluded from survival analysis as they were treated with CHOP chemotherapy due to misdiagnosis early in the study period. Staging was done by chest xray, abdominal ultrasound, and bone marrow biopsy. Participants were treated with ABVD chemotherapy and, if HIV+, concurrent antiretroviral therapy (ART). Post-progression therapy is generally limited to salvage chemotherapy regimens without access to radiation or autologous stem cell transplant. RESULTS: 38 participants were enrolled with mean age 29 years (SD 11). Twenty-one (55%) were men, and eleven (21%) were HIV+, of whom eight (73%) were on ART at HL diagnosis. Twenty-five (65%) participants had advanced stage disease and thirteen (35%) had limited stage disease, of whom ten were unfavorable risk and three were favorable risk. Bulky disease (at least one lymph node >10cm) was present in 29 (76%) participants at enrollment. Median CD4 count was 138 cells/mL (IQR 102-298) and 10 (91%) had an HIV viral load <400 copies/mL. Participants received a median six cycles (i.e. twelve doses) ABVD. Grade 3/4 neutropenia occurred in 15 (42%) but there were only two (5%) episodes of neutropenic fever and one episode of grade 3/4 anemia. There were no documented episodes of any grade cardiac or pulmonary toxicity. One patient was lost to follow-up, one patient absconded and died early in therapy, and one patient absconded and died during salvage therapy with median follow up 36 months for patients still alive at administrative censoring. Among patients with evaluable disease (n=34), 27 (79%) achieved a CR, three (9%) achieved a PR, and four (12%) had progressive disease. Among patients with limited stage disease, 2-yr overall survival (OS) and progression-free survival (PFS) were 92% and 80%, respectively. Among patients with advanced stage disease, 2-yr overall survival (OS) and progression-free survival (PFS) were 75% and 61%, respectively (see FIGURE). There was no difference in survival by HIV status. Of eleven deaths during the study period, nine (82%) were due to disease progression, one due to therapy-related sepsis, and one due to other causes. CONCLUSION: Here, we present, to our knowledge, the most complete prospective clinical and outcome data of pathologically confirmed Hodgkin lymphoma in sub-Saharan Africa. Most patients with HL in Malawi, a low-income country, present with advanced or unfavorable risk HL. With standard chemotherapy in the form of ABVD, long-term cure is possible, and in fact, probable, for patients presenting with HL in Malawi. The majority of deaths are attributed to disease progression and not to adverse events. However, there remains a marked disparity between outcomes in Malawi and in high-income countries and improvements through both clinical and implementation research are urgently needed to accelerate diagnosis at a lower stage and to provide therapeutic options for those who fail ABVD. Figure Caption: Overall survival and progression-free survival of Hodgkin lymphoma patients treated with ABVD in Malawi. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Long-Term Outcomes of High-Risk Stage 1/2 Classic Hodgkin Lymphoma Managed with an Advanced Stage Treatment Approach

Background: The definition of advanced stage classic Hodgkin lymphoma (cHL) may vary, with bulky stage 2A (> 10cm or > 33% of transthoracic diameter otherwise described as 'large mediastinal adenopathy’ (LMA)) and/or stage 2B with risk factors, included in some studies and clinical guidelines. The ECHELON 1 study recently demonstrated improved overall survival (OS) using AVD-brentuximab vedotin (BV) compared with ABVD in stage 3/4 cHL (Ansell et al. NEJM 2022). Similarly, the pediatric combination BV-AVE-PC demonstrated improved event free survival (EFS) over ABVE-PC in a phase 3 trial of 'high risk patients (pts)’ age 2-21 years (y) (AHOD1331), a definition that included stage 2B bulky (LMA) pts, with a significant benefit shown in this subgroup (HR 0.09 (0.01-0.69)) (Castellino et al. ASCO 2022). Thus, re-evaluation of 'advanced stage’ definitions is warranted, especially in the adult population. Herein, we evaluated the long-term outcomes of pts with stages 1/2 bulky and 2B, a group that has been uniformly included in our advanced stage management approach. Methods: The BC Cancer Lymphoid Cancer Database was screened to identify all pts 16-70 y with 1/2A bulky (≥ 10 cm) and 2B (± bulky) disease treated with ABVD chemotherapy. Since 2005, advanced stage cHL pts in BC have been managed with 6 cycles of ABVD and PET-guided consolidative RT, whereby those with an EOT PET positive (pos) scan received RT. Following report of the RATHL trial in 2015, those pts with an interim PET2 negative (neg) scan had bleomycin omitted from the latter 4 cycles. For the current study, PET scans assessed by the IHP criteria were re-reviewed to assign a Deauville (D) score (PET-neg=D1-3, DX; PET-pos=D4-5). Freedom from treatment failure (FFTF) was measured from diagnosis to relapse/ progression of HL, or death due to HL or treatment toxicity. Results: From 2005-2020, 295 pts (148 M, 147 F) were identified. By stage: 1A bulky n=2, 2A bulky n=71 (henceforth called 'bulky only’ n=73); 2B n=133; 1B bulky n=3, 2B bulky n=86 (henceforth called stage 1/2B bulky n=89). Median age was 30 y (range 17- 69 y), median mass size 10 cm overall and 11 cm in bulky cases (range 10-20 cm). Of those with bulky disease (n=162), 147 (91%) had a bulky mediastinal mass. Using the reverse Kaplan-Meier method, median follow-up was 9.3 y (0.9 -17.3 y). The 5 y FFTF and OS for all pts were 84% and 94%. By stage groups, 5 y FFTF estimates were: 90% for bulky only, 82% in 2B, and 81% in 1/2B bulky pts (p=0.29) (Figure 1a), while corresponding 5 y OS estimates were 95%, 93%, and 94%, respectively (p=0.52) (Figure 1b). An EOT PET was performed in 250 pts and an additional 11 patients were included who only had a PET2-neg scan which was not repeated (total PET scan n= 261). The main reason for not having a PET scan was absence of residual mass on CT scan (21/34); 2 patients had progressive disease (PD) while on treatment (both stage 2B). In total 208/261(80%) had a PET-neg scan (2 pts received RT), and 53/261 (20%) had an EOT PET-pos scan of which, 32 (63%) received RT (mediastinal RT, 30/32). Stage 1/2B bulky cases were more likely to have a PET-pos scan (1/2B 32% vs 2B 18% vs bulky only 10%, p=0.002), and as a result, were more likely to receive RT (1/2B bulky 23% vs 2B 9% vs bulky only 6%, p=0.003). Overall, the 5 y FFTF was superior in PET-neg cases (93% vs 49%, p<0.001 (and 62.5% in PET-pos pts who received RT)), and 5 y OS was 96% vs 88% (p=0.17). For the 259 cases in which the D score was available, 5 y FFTF was similar across PET-neg D categories: DX 95%; D1 92%; D2 94%; D3 93%. For all DX-3, 5y FFTF was 94%, and superior to both D4 70% and D5 17% (p<0.001). Corresponding 5 y OS estimates for DX-D3, D4, and D5, were 96%, 95%, and 77%, respectively, with only the latter demonstrating an inferior prognosis (p=0.005). An EOT D5 PET scan was more common in pts with B symptoms: stage 1/2B bulky cases 12/83, 14.5%; 2B 10/106, 9%; bulky only 2/70, 3% (p=0.048). Conclusion: Applying an advanced stage management approach yields excellent outcomes, particularly in the 80% of patients with a PET-neg scan. Further, use of a PET-scan limited RT use to only 6% of pts with stage 1/2A bulky disease. However, those with stage 1/2B bulky disease have a higher likelihood of an EOT PET-pos scan and subsequent RT. Further, an EOT PET D5 score was more common in those with B symptoms overall, especially when coupled with bulky disease. This data provides further rationale for consideration of BV with upfront therapy in other advanced stage subgroups. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Prognostic Significance of Serum Beta-2 Microglobulin (sβ2m) Levels in Patients with Hodgkin Lymphoma (HL): Final Analysis on 915 Patients Treated with ABVD or Equivalent (ABVDeq) Chemotherapy or Combined Modality Therapy (CT/CMT) Focusing to the Determination of Optimal Cut-Offs

Objective/Aim: Sβ2m is a well- established prognostic factor for several hematologic malignancies, but its role in HL is still controversial. We aimed to investigate the prognostic significance of sβ2m levels in a large series of homogenously treated HL patients. Methodology: We analyzed 915 patients with HL treated with ABVDeq (1990-2019) and selected solely based on the availability of pretreatment sβ2m levels. Sβ2m levels (upper normal limit 2.4mg/L) were analyzed in relation to other baseline features and the outcome. Freedom From Progression (FFP) was defined as time between treatment initiation and treatment failure (toxic death, primary refractoriness, PR with switch to alternative chemotherapy or relapse); deaths of unrelated causes were censored. Overall Survival (OS) and Disease-Specific Survival (DSS) were measured from treatment initiation to death of any cause or HL-related causes respectively. Sequential cut-offs (1.8-3.5 by 0.1mg/L increments) were used to explore the potential impact of sβ2m on outcomes. Results: The median serum β2m levels were 2.20mg/L (IQR 1.80-3.00, range 0.50-14.40) and 383/915 patients (42%) had elevated levels (>2.4mg/L). Sβ2m correlated strongly with all baseline features. Univariate Analysis: FFP was significantly inferior in patients with higher β2m at all tested cut-offs. At 2.4 mg/L ("normal versus high") the 10-year FFP was 80% vs 70% (p=0.001) after a median follow-up of 81.1 months. However, the best cut-off was 2.0mg/L [10-year FFP 83% vs 70% (p=0.001)]. A dose-response relationship was seen across quartiles Q1-4 with 10-year FFP 84%,78%,73% and 68% (p=0.001). In early stages (IA/IIA), statistically significant results were obtained at cut-offs between 1.8 and 2.1mg/L. The best cut-off was 1.9mg/L [10-year FFP 88% vs 78% (p=0.003)]. In advanced stages, none of the cut-offs yielded statistically significant results (borderline at 2.0mg/L; 10-year FFP 74% vs 64%, p=0.09). Multivariate Analysis: Sβ2m levels remained significant for FFP after adjustment for IPS factors, ESR and B-symptoms at 2.0mg/L [hazard ratio (HR) 1.55, p=0.01) in the whole series of 915 patients; it was not significant at the "normal versus high" comparison at 2.4mg/L. In early stages, sβ2m was a significant predictor of FFP at both cut-offs of 2.0 mg/L and 2.4 mg/L (HR 1.65, p=0.034 and 1.67, p=0.038). In advanced stages, sβ2m was an independent prognostic factor for FFP at 2.0mg/L (HR 1.44, p=0.098 despite the lack of univariate significance), but not at 2.4mg/L. The 10-year OS and DSS was lower in patients with elevated β2m levels (10-year rates 90% vs 77%, p<0.001 and 93% vs 86%, p=0.002). Similar results to FFP were obtained by multivariate analysis of DSS for all 915 and early-stage patients. Conclusion: Higher sβ2m was a significant independent predictor of FFP in HL but the optimal cut-off appears to lie within the normal limits, performing better than a "normal versus high" evaluation (cut-off 2.4 mg/L) and being 2.0mg/L for the whole series and 1.9 mg/L for early-stage patients. The prognostic significance in advanced stages was weaker (best cut-off 2.0 mg/L). Serum β2m was also highly predictive of OS and DSS. An analysis of corrected serum β2m according to renal function is ongoing.

Decisional Role of Interim PET in Relapsed/Refractory Classical Hodgkin Lymphoma Treated with Begev Chemotherapy As First Salvage

Achievement of complete response (CR) before autologous stem cell transplantation (ASCT) is one of the main predictive factors of outcome in patients (pts) affected by relapsed/refractory (R/R) classical Hodgkin Lymphoma (cHL) eligible to high-dose chemotherapy. The predictive role of interim PET during salvage treatment is well established in pts treated with IGEV or ICE but has not been investigated in pts receiving BEGEV (Bendamustine, Gemcitabine and Vinorelbine) as first salvage treatment. With the aim to investigate the predictive value of PET after 2 cycles of BEGEV (PET2) in terms of CR rate and survival, we retrospectively collected data of consecutive R/R cHL pts eligible to ASCT treated from 2011 to 2021 in 3 Italian centres. PET scans were locally evaluated using Deauville Score (DS), considering a score 1-3 negative and consistent with CR. Early relapse was defined as a relapse occurring ≤12 months from the end of first-line therapy. Survival functions were calculated from the date of initiation of BEGEV chemotherapy. Ninety-four cHL R/R pts receiving BEGEV as first salvage therapy were included. Fifty-one (54.3%) pts were male. First-line therapy consisted in 2 to 6 ABVD chemotherapy cycles accordingly to clinical stage followed by consolidation radiotherapy (RT) in 24 (25.5%) pts. At relapse, median age was 37 years (range: 18-71 years), 51 (54.3%) pts were in stage III-IV, 16 (17%) pts had B symptoms and 34 (36.2%) pts had extranodal involvement (EI). Fifty-one (54.3%) pts were primary refractory, 23 (24.5%) pts had an early and 20 pts (21.3%) a late relapse. PET2 was performed in 86 (91.5%) pts, and resulted negative in 61 (70.9%) and positive in 25 (29.1%) pts (DS 4 in 17 and DS 5 in 8 pts). PET after 4 BEGEV cycles (PET4) was performed in 82 (87.2%) pts and resulted negative in 63 (67%) and positive in 19 (20.2%) pts (DS 4 in 10 and DS 5 in 9 pts). Complete response after 4 BEGEV was achieved in 55/61 (90.2%) PET2 negative pts and 7/25 (28%) PET2 positive pts. Considering pts evaluable for both PET2 and PET4, PET2 positive pts had a statistically lower probability to achieve CR at PET4 when compared to PET2 negative pts (Odds ratio: 0.07, CI 95%: 0.02-0.29; p<0.00001). Autologous SCT was performed in 81 (86.2%) pts, following BEGEV in 56 pts (69.1%) and after further salvage treatments in 25 (30.9%). A post-ASCT consolidation strategy was performed in 24 (29.6%) pts, and consisted in RT in 18 pts and brentuximab-vedotin in 6 pts. Ten pts received an allotransplant: in 3 cases allotransplant was planned in a tandem modality, while in 7 cases was performed after further salvage treatments for post-ASCT relapse or progression. With a median follow-up of 36.4 months (interquartile range: 20.1-50.0), 3-years overall survival (OS), progression-free survival (PFS) and event-free survival (EFS) for the whole study population were 91.7%, 61.6% and 53.9%, respectively. No significant differences in OS were detected according to PET2 result. Conversely, both 3-years PFS and EFS were significantly superior in PET2 negative vs PET2 positive pts: 3-years PFS was 61.6% (CI 95%: 52.1-72.9) in PET2 negative and 43.6% (CI 95%: 27.9-68.4) in PET2 positive pts (p=0.0004) (Figure 1), while 3-years EFS was 71% (CI 95%: 59.8-84.3) and 23.3% (CI 95%: 11.3-48.1), (p<0.001). Univariable analysis of PFS was performed using Cox regression model and evaluating adverse risk factors at relapse (primary refractory and early relapse vs late relapse, presence of EN involvement and B-symptoms) and demonstrated a significantly inferior PFS for pts with EI (HR 1.94, CI 95% 1.01-3.74, p=0.47) and primary refractory disease or early relapse (HR 2.02, CI 95%: 1.01-4.04, p=0.047), but not for pts with B symptoms (HR 1.05, CI 95%: 0.43-2.51, p=0.9). Multivariate Cox regression model of PFS evaluating presence of EI at relapse (HR 1.55 , CI 95%: 0.74-3.25, p=0.240), time to relapse (primary refractory and early relapse vs late relapse, HR 0.84 (CI 95%: 0.36-1.96, 0.683) and PET2 result, identified PET2 positivity as the only predictive factor for PFS (HR 3.24, CI 95%: 1.55-6.77, p=0.002). In conclusion, R/R cHL pts with PET2 positive during BEGEV salvage treatment had a lower probability to achieve CR after 2 additional BEGEV cycles and a significantly inferior PFS, and could benefit from early exposure to new therapeutic strategies before ASCT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

NCMP-01. CEREBRAL ANGIOSARCOMA AND DISTANT RADIATION THERAPY

Abstract Angiosarcoma is a rare malignant tumor originating from vascular endothelial cells. Typically, the diagnosis of angiosarcomas carry poor prognosis. Radiation exposure is one of the most common risk factors for angiosarcomas. Due to the rarity of angiosarcoma, there is sparse literature, hence it is mostly seen in case reports. We describe a case of cerebral angiosarcoma with an unknown primary malignancy in a patient with distant history of non-Hodgkin’s lymphoma treated with chemotherapy and radiation therapy to the thorax. A 54 year old male with a history of Non-Hodgkin’s Lymphoma was treated with ABVD chemotherapy and thoracic radiation therapy in 1995,presented for bilateral vision loss. Neurologic examination revealed a left homonymous hemianopia .Further investigation with brain Magnetic Resonance Imaging revealed hemorrhagic lesions in the bilateral frontal and in the right parietal-occipital lobes. Computed tomography of the chest, abdomen, and pelvis was negative for malignancy. The patient underwent a right occipital craniotomy with resection of right parietal occipital lesion. Histopathology revealed metastatic angiosarcoma. It has been acknowledged that exposure to external beam radiotherapy puts patients at risk for angiosarcoma in the future. It is believed that radiation may induce the development of AS by several mechanisms. One mechanism is the direct oncogenic effect of ionizing radiation, which can damage DNA, leading to genome instability and mutation of cancer-related genes. A prior literature review noted twenty cases of angiosarcoma developing following therapeutic irradiation. Our particular patient’s prior exposure to irridation did not include a brain radiation field, so it is unlikely this patient had radiation induced angiosarcoma.Furthermore, it does not appear that his prior radiation exposure explains the location of his angiosarcoma as his radiation field was localized to chest. Although angiosarcoma is rare, it deserves further investigation to increase the knowledge base on etiology of metastasis.

Cost-Effectiveness of PET Directed Versus Combined Modality Therapy for Early-Stage Favorable Hodgkin's Lymphoma.

The standard of care for early-stage Hodgkin Lymphoma (HL) is combined modality therapy (CMT) consisting of chemotherapy and involved site radiation therapy (ISRT). Recent treatment de-escalation trials have assessed the impact of omitting radiation with the use of positron emission tomography (PET) and have suggested a detriment in progression free survival (PFS) for patients who do not receive radiation therapy (RT) but similar overall survival. The purpose of this study was to compare the cost-effectiveness of PET-directed therapy versus standard of care CMT. This study used a cost-effectiveness Markov model simulating 5 year outcomes for 1 million patients with early-stage HL treated with either PET-directed therapy consisting of 2 cycles of ABVD chemotherapy ± ISRT or CMT consisting of 2 cycles of ABVD+ISRT. Patients progressed to no evidence of disease, progression of disease (PD), or death. Patients with PD underwent salvage therapy with high dose chemotherapy and stem cell transplant (HDC-SCT). The primary outcome measured was the incremental cost-effectiveness ratio. Deterministic sensitivity analyses were performed. We found that PET-directed therapy and CMT strategies were associated with costs of $47,362 and $41,167, respectively. The CMT strategy was equally as effective as the PET-directed therapy strategy with QALYs of 3.4. On 1-way sensitivity analyses, the model was most sensitive to CMT and HDC-SCT costs. Two-way sensitivity analyses showed the model was sensitive to the relative costs of these treatments. For patients with early-stage HL, CMT is the cost-effective strategy as compared with PET-directed therapy.

The effect of the surgical treatment in the complex management on life expectancy of thymic Hodgkin's lymphoma

The result of treatment of primary Hodgkin's lymphoma lesion of the thymus gland of a 26-year-old patient is presented. At the preoperative stage of examination, tumor maligna cells were obtained during puncture of mediastinal formation. The diagnosis is malignant tumor of the mediastinum. Considering this, a surgical treatment was performed-radical removal of the mediastinal tumor. After the study of the postoperative drug, a clinical diagnosis was made: lymphogranulomatosis, a massive (bulky) tumor lesion of the mediastinum, stage IIХ, after surgical treatment. First course of ABVD chemotherapy was performed 28 days after the operation. When performing the second course of chemotherapy according to the same scheme, the patient developed complications in the form of moderate leukocytopenia (leukocytes, 0.9109/l) and stomatitis. Special treatment was discontinued, and the patient was observed by an oncologist in the polyclinic of an oncological dispensary.&#x0D; At the next examination, which was performed 11 months later, a relapse of the disease was identified. Considering the preservation of persistent leukopenia (leukocytes, 3.0109/l), it was decided to conduct six courses of ABVD polychemotherapy with prednisone, against the background of G-CSF. At this stage of oncology, the main method of treating Hodgkin's lymphoma is chemo-hormone therapy in combination with radiation therapy. The performed non-standard complex treatment is radical surgical removal of a mediastinal tumor followed by polychemotherapy. It allowed 4 years after the completion of treatment to know motherhood, which did not affect the patient's health. As indicated by the long relapse, free period of the disease is 16 years, and life expectancy is 18 years.

P097: The status quo of involved-field radiotherapy – Quality analysis of radiotherapy in the GHSG HD 16

Question: The HD 16 trial of the German Hodgkin Study Group (GHSG) investigated the use of consolidative radiotherapy (RT) after 2 cycles of ABVD chemotherapy for early-stage Hodgkin lymphoma (HL) and could demonstrate the superiority of a combined modality approach [1]. The present work aims at analyzing the quality of involved-field RT used in this study. Methods/Material: For quality assessment, 100 randomly chosen plans from the HD 16 trial were requested and analyzed. RT was assessed by experts of the radiation therapy panel of the GHSG using initial (staging) imaging, RT plans and the recommendation forms by the reference radiation oncology. Evaluation was graded as „correct“, „minor deviation“ or „major deviation“. Statistical analyses were performed using SPSS (version 27/28, IBM, NY, USA). Results: Radiation doses were adequate with a median of 20 Gy (19.8 Gy-21.6 Gy) in normofractionation. In the majority of radiation series, supradiaphragmatic target volumes were treated (91 %), with the regions most commonly irradiated being supraclavicular left/right (73 % each), infraclavicular left/right (73 % each) and cervical left/right (44 % and 45 %, respectively). Acute treatment toxicities were mild to moderate with only 3 cases of grade 3–4 toxicities (1 nausea/vomiting, 1 dysphagia, 1 mucositis). According to the RT panel, 84 % of cases were evaluated as „correct“, 5 % as „minor deviations“ and 11 % as „major deviations“. Major deviations were caused by insufficient dose coverage of involved regions in most cases (10/11), predominantly in the upper mediastinum (5/10 cases). Previous GHSG studies in early-stage HL (HD 10 [2] and HD 13 [3]) showed lower rates of RT series according to protocol (38.8 % and 52 %, respectively). A χ2-test was used to compare the number of correct RT series in the different GHSG study generations (HD 13 vs. HD 16). No expected cell frequencies were below 5. Results reveal a significant improvement in favor of HD 16 (χ2(1)=33.8, p<0.001 Φ=-0.247). Similar outcomes were found for the association of GHSG study generation and the absence of major deviations (χ2(1)=27.4, p<0.001 Φ=- 0.222). Conclusion: Since its introduction in HD10, involved-field RT has evolved considerably. However, continuous efforts in RT quality assurance and training are needed in the modern era. Literature 1.JCO. November 2019; 37(31):2835-2845. 2.IJROBP. August 2008; 71 (5):1419-1424. 3.SUON. February 2017;193(2):109-115.

Classical Hodgkin Lymphoma: A Joint Clinical and PET Model to Predict Poor Responders at Interim Assessment.

(1) This study aimed to investigate whether baseline clinical and Positron Emission Tomography/Computed Tomography (bPET)-derived parameters could help predicting early response to the first two cycles of chemotherapy (Deauville Score at interim PET, DS at iPET) in patients with classical Hodgkin lymphoma (cHL) to identify poor responders (DS ≥ 4) who could benefit from first-line treatment intensification at an earlier time point. (2) cHL patients with a bPET and an iPET imaging study in our Centre’s records (2013–2019), no synchronous/metachronous tumors, no major surgical resection of disease prior to bPET, and treated with two cycles of ABVD chemotherapy before iPET were retrospectively included. Baseline International Prognostic Score for HL (IPS) parameters were collected. Each patient’s bPET total metabolic tumor volume (TMTV) and highest tumoral SUVmax were collected. ROC curves and Youden’s index were used to derive the optimal thresholds of TMTV and SUVmax with regard to the DS (≥4). Chi-square or Fisher’s exact test were used for the univariate analysis. A multivariate analysis was then performed using logistic regression. The type I error rate in the hypothesis testing was set to 5%. (3) A total of 146 patients were included. The optimal threshold to predict a DS ≥ 4 was >177 mL for TMTV and >14.7 for SUVmax (AUC of 0.65 and 0.58, respectively). The univariate analysis showed that only TMTV, SUVmax, advanced disease stage, and age were significantly associated with a DS ≥ 4. A multivariate model was finally derived from TMTV, SUVmax, and age, with an AUC of 0.77. (4) A multivariate model with bPET parameters and age at diagnosis was satisfactorily predictive of poor response at iPET after ABVD induction chemotherapy in cHL patients. More studies are needed to validate these results and further implement DS-predictive factors at baseline in order to prevent poor response and intensify therapeutic strategies a-priori when needed.

Hodgkin lymphoma and female fertility: a multicenter study in women treated with doxorubicin, bleomycin, vinblastine, and dacarbazine

AbstractPreservation of fertility has become a growing concern in young females with Hodgkin lymphoma (HL). However, the rate of pregnancy after the current most frequently prescribed ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and darcarbazine) chemotherapy for HL has rarely been studied. In this study, we aim to determine the impact of ABVD on the fertility of women treated for HL. We conducted a noninterventional, multicenter study of female patients of childbearing age who were treated for HL. Two healthy apparied women nonexposed to chemotherapy (our controls) were assigned for each patient. Fertility was assessed by the number of pregnancies and births after HL treatment. Sixty-seven patients were included. The median age at diagnosis was 24.4 years (range, 16-43). HL was a localized disease for 68.7%. Of all the patients, 53.7% started at least 1 pregnancy after treatment vs 54.5% of the controls (P = .92). Of all the patients who desired children, 81% had at least 1 pregnancy. Patients treated with ABVD did not have a longer median time to pregnancy (4.8 years in the group of patients and 6.8 years for controls). Across patients, there were 58 pregnancies and 48 births (ratio, 1:2) and 136 pregnancies and 104 births (ratio, 1:3) for the control cohort. No increase in obstetric or neonatal complications has been reported in HL in our study. The number of pregnancies, births, and the time to start a pregnancy in young women treated with ABVD for HL is not different from that of controls. Therefore, females with HL treated with ABVD should be reassured regarding fertility.

Milestones in Hematology and Oncology: From Fatal to Curable Disease.

Background: The comprehensive management of patients with Hodgkin's lymphoma (HL) is a success story in contemporary oncology. Over the past decades, the survival rate of patients with HL has significantly improved. The objective of this analysis is to evaluate and document the progress in the management of Hodgkin's lymphoma in patients in our country, reflected in their vital statistics, over time periods defined by the respective standard of treatment. Material and methods: The present study is designed as a retrospective-prospective study. We analyzed different modalities of treatment and compared 5 and 10-year overall survival rates in a total of 588 Hodgkin's lymphoma patients treated at the University Clinic for Hematology in Skopje during two consecutive time periods, before 2000 and after 2000. The entire observation period is from 1980 to 2020. All patients are above the age of 14, with a documented histopathological diagnosis of Hodgkin's lymphoma and with evaluable medical documentation, including clinical and laboratory data on their initial condition, the administered therapy, as well as the clinical follow-up of the patients. Results: The basic clinical features of the analyzed population across the two periods correlate with those reported in the relevant medical literature, with only slight deviations. Ten-year overall survival rates improved by 31.7% through the two calendar periods. During the last two decades of the previous century (1980-2000) the initial treatment options were COPP and COPP-like regimens for the vast majority of patients (94.7%), leading to disease remission in 80% of them. After 2000, 95.8% of de novo diagnosed patients have been treated with ABVD chemotherapy as a frontline choice and the complete response rate is 88.4%. We confirmed the superiority of ABVD in terms of efficacy, improved tumor and disease control, as well as its long-term clinical outcome. While in the past we had very limited options for relapsed/refractory HL patients, the analysis of the results of HL patients treated with various therapeutic approaches in the latter period, defines BEACOPP as the preferred choice. High-dose chemotherapy, followed by autologous hematopoietic stem cell graft, as a strategy for our R/R patients in the timeframe after 2000, ensures a 5-year overall survival for 51% of them, whereas 45% of the patients survive more than 10 years. Conclusion: This analysis from our Hodgkin's lymphoma database illustrates that there has been tremendous improvement in the long-term survival rates since the turn of this century. At our institution we strive to implement positive trends in practice, as suggested by relevant guidelines, regarding the evolution and progress in the diagnostic workup, treatment, and the overall management of patients with Hodgkin's disease. The objective would be to secure favorable vital statistics for our patient population, now reaching 83.5% at 10 years, which closely correlates with the data of more developed countries and centers. In future clinical trials we will also evaluate the efficacy of brentuximab-vedotin and new PD-1 blocking antibodies.

The Association of Programmed Death Ligand 1 (PD-L1) and Cluster of Differentiation 95 Ligand (CD95L) Immunoexpression with Chemotherapy Response in Classical Hodgkin Lymphoma

Background: Programmed Death Ligand (PD-L1) and Cluster of Differentiation 95 (CD95L) are influenced by oncogenes and function in the anti-apoptosis process which is thought to play a role in chemotherapy resistance. This study aimed to analyze the association of PD-L1 and CD95L immunoexpression with chemotherapy response in Classical Hodgkin Lymphoma (CHL).Method: This study involved 40 cases of histopathologically diagnosed CHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PD-L1 and CD95L immunohistochemical staining were performed in selected paraffin-embedded tissue blocks of all cases. The chemotherapy response status of the patients was taken from the medical recordResults: High PDL-1 immunoexpression was evident in 19 (47.5%) cases while positive CD95L immunoexpression was found in 14 (35%) CHL cases. High PD-L1 immunoexpression was significantly associated with the Non-Responsive (NR) group (78.9%) with p-value = 0.0001. Positive CD95L immunoexpression was greater in the NR group (71.4%) with p-value = 0.37.Conclusion: : High PD-L1 immunoexpression indicated an unfavorable response to ABVD chemotherapy in CHL. CD95L immunoexpression was not associated with ABVD chemotherapy response in CHL.