Unfavorable early-stage Hodgkin lymphoma: assessment of patient characteristics in a real-world setting.

Aim: Unfavorable prognostic factors among classical Hodgkin lymphoma (cHL) patients in the real-world setting have yet to be fully characterized. Methods: In this retrospective study using the ConcertAI Oncology Dataset, patient characteristics, unfavorable prognostic factors and treatment patterns were evaluated among patients diagnosed with cHL. Results: Among 324 adult cHL patients diagnosed 2016-2021, 16.1% were classified as early favorable, 32.7% early unfavorable and 51.2% advanced disease. Early unfavorable patients were younger and had a larger nodal mass. The prognostic factor B symptoms was most frequently documented in early unfavorable patients (59.4%), followed by bulky disease (46.2%), >3 involved lymph node regions (31.1%), and erythrocyte sedimentation rate ≥50 (25.5%). Conclusion: In this analysis of real-world data, we found that nearly a third of newly diagnosed cHL patients had early unfavorable disease. Our analysis also showed differences in the proportion of patients for each unfavorable factor among patients with early-stage unfavorable cHL.

What is this article about? Lymphoma is a type of blood cancer that develops when white blood cells grow out of control. This study looked at a certain type of lymphoma called classical Hodgkin lymphoma (cHL). Patients with cHL are put into groups based on risk factors. Risk factors mean the cancer had certain characteristics that make it more likely to spread to other body parts and more difficult to treat. These can be symptoms like drenching night sweats, unexplained fever, sudden weight loss, or large swellings of the infection fighting glands of the body.What did we do? We studied the risk factors of patients with cHL, using data from electronic medical records. What were the results? About a third of the patients in this study had early stage cHL with unfavorable risk factors, and over half of the patients had advanced stage cHL. The patients who had early stage cHL with unfavorable risk factors were younger and had a larger lump in a lymph node. More than half of the patients experienced drenching night sweats, unexplained fever, or weight loss of more than 10%. What do the results mean? We found that nearly a third of new cHL patients had early-stage cHL with unfavorable risk factors. We also showed differences in the number of patients with each unfavorable risk factor among patients with early-stage unfavorable cHL. This study can help doctors and researchers group patients and determine the best treatment or research study for patients who have cHL.

Treatment patterns and clinical outcomes among patients with relapsed/refractory classical Hodgkin's lymphoma.

Aim: Limited real-world data exist on treatment patterns and clinical outcomes for patients with relapsed/refractory (R/R) classical Hodgkin's lymphoma (cHL). Methods: This study used the ConcertAI Oncology Dataset to assess treatment patterns, real-world progression-free survival (rwPFS), and real-world overall survival (rwOS) in adults with R/R cHL diagnosed from 2000 to 2019. Results: Among 226 (79%) treated patients, there was substantial treatment heterogeneity. Median rwPFS was 21.0 months in the second line (2L) of therapy. Median rwOS was 146.7 months in 2L and decreased to 40.6 months in the fifth line. Conclusion: Patients were exposed to a myriad of treatments in the R/R setting. These data support a relation between rwPFS and rwOS and highlight the need for effective therapeutic options.

Quality-of-life analysis of pembrolizumab vs brentuximab vedotin for relapsed/refractory classical Hodgkin lymphoma.

KEYNOTE-204 (NCT02684292) demonstrated a progression-free survival advantage for pembrolizumab over brentuximab vedotin (BV) in patients who had relapsed or refractory classical Hodgkin lymphoma (R/R cHL) following, or who were ineligible for, autologous stem cell transplantation (ASCT). Health-related quality of life (HRQoL), measured by patient-reported outcomes (PROs) from KEYNOTE-204, are reported from patients who received ≥1 dose of study treatment and completed ≥1 PRO assessment. The EORTC QoL Questionnaire Core 30 (QLQ-C30) and EuroQoL EQ-5D were administered at baseline, every 6 weeks until week 24, and every 12 weeks thereafter. Prespecified end points included least squares mean (LSM) changes from baseline to week 24 and time to true deterioration (TTD; ≥10-point decline from baseline). Comparisons were evaluated using 2-sided P values uncontrolled for multiplicity. High compliance at baseline (>90%) and through week 24 (>80%) was demonstrated across treatment groups (PRO analysis set: pembrolizumab, n = 146; BV, n = 150). The EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) score improved from baseline to week 24 on pembrolizumab and worsened on BV and demonstrated significant LSM differences at 24 weeks (GHS/QoL: 8.60 [95% confidence interval, 3.89-13.31]; P = .0004). Significant improvements were observed in each QLQ-C30 domain except emotional and cognitive functioning. Compared with BV, pembrolizumab prolonged TTD for GHS/QoL (hazard ratio, 0.40 [95% CI, 0.22-0.74]; P = .003) and each QLQ-C30 domain except cognitive functioning. In conclusion, pembrolizumab demonstrated overall improvements in PROs of HRQoL measures over BV in the KEYNOTE-204 study. These data and previously reported efficacy results support pembrolizumab as the preferred treatment option for patients with R/R cHL who are ineligible for or experience relapse after ASCT.

Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study.

BACKGROUND: PD-1 blockade via pembrolizumab monotherapy has shown antitumour activity and toxicity in patients with relapsed or refractory classical Hodgkin lymphoma. Here, we present interim analyses from the KEYNOTE-204 study evaluating pembrolizumab versus brentuximab vedotin for relapsed or refractory classical Hodgkin lymphoma. METHODS: In this randomised, open-label, phase 3 study, patients aged 18 years or older with relapsed or refractory classical Hodgkin lymphoma with measurable disease and an Eastern Cooperative Oncology Group performance status of 0 or 1 who were ineligible for or had relapsed after autologous haematopoietic stem-cell transplantation (HSCT) were enrolled at 78 hospitals and cancer centres in 20 countries and territories. Patients were randomly assigned (1:1) with an interactive voice response system to pembrolizumab 200 mg intravenously every 3 weeks or brentuximab vedotin 1·8 mg/kg intravenously every 3 weeks. Randomisation was stratified by previous autologous HSCT and status after front-line therapy. Results from the second interim analysis are presented here, with a database cutoff of Jan 16, 2020. The dual primary endpoints assessed in the intention-to-treat population were progression-free survival as assessed by blinded independent central review, and overall survival (not analysed at this interim analysis). Safety was assessed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, NCT02684292. Recruitment for this trial is closed. FINDINGS: Between July 8, 2016, and July 13, 2018, 151 patients were randomly assigned to pembrolizumab and 153 to brentuximab vedotin. After a median time from randomisation to data cutoff of 25·7 months (IQR 23·4-33·0), median progression-free survival was 13·2 months (95% CI 10·9-19·4) for pembrolizumab versus 8·3 months (5·7-8·8) for brentuximab vedotin (hazard ratio 0·65 [95% CI 0·48-0·88]; p=0·0027). The most common grade 3-5 treatment-related adverse events were pneumonitis (six [4%] of 148 patients in the pembrolizumab group vs one [1%] of 152 patients in the brentuximab vedotin group), neutropenia (three [2%] vs 11 [7%]), decreased neutrophil count (one [1%] vs seven [5%]), and peripheral neuropathy (one [1%] vs five [3%]). Serious treatment-related adverse events occurred in 24 (16%) of 148 patients receiving pembrolizumab and 16 (11%) of 152 patients receiving brentuximab vedotin. One treatment-related death due to pneumonia occurred in the pembrolizumab group. INTERPRETATION: Pembrolizumab showed statistically significant and clinically meaningful improvement in progression-free survival compared with brentuximab vedotin, with safety consistent with previous reports. These data support pembrolizumab as the preferred treatment option for patients with relapsed or refractory classical Hodgkin lymphoma who have relapsed post-autologous HSCT or are ineligible for autologous HSCT. FUNDING: Merck Sharp & Dohme Corp (a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA).

Real-World Healthcare Resource Utilization in Patients with Classical Hodgkin Lymphoma Treated with Pembrolizumab and Nivolumab in the USA.

BACKGROUND: Patients with classical Hodgkin lymphoma (cHL) relapsed or refractory (R/R) disease who relapse after or are ineligible for autologous stem cell transplantation have a poor prognosis. Recently, the anti-PD1 monoclonal antibodies nivolumab and pembrolizumab were approved by the US Food and Drug Administration (FDA; May 2016 and March 2017, respectively) as treatment options for R/R cHL patients. OBJECTIVE: In the absence of comparative clinical trials between these agents, this observational study was conducted to evaluate the healthcare resource utilization (HRU) of patients with cHL initiated on pembrolizumab compared to nivolumab in the USA. PATIENTS AND METHOD: Healthcare insurance claims from Symphony Health's IDV® (Integrated Dataverse) (July 2014-June 2018) were used in this retrospective study. The study population included adult patients with cHL initiated on pembrolizumab or nivolumab (index date). Inverse probability of treatment weighting was used to adjust for differences in patient characteristics between cohorts. All-cause and cHL-related hospitalizations and outpatient visits were measured during the observation (post-index) period and reported per patient-year (PPY). Rates of HRU were compared between cohorts using rate ratios (RRs). RESULTS: A total of 92 and 218 patients initiated on pembrolizumab and nivolumab, respectively, were included in the study population. After weighting, the mean age was similar at 55 years in both cohorts, while the proportion of females was lower in the pembrolizumab cohort (35.3%) compared to the nivolumab cohort (44.1%). Mean Quan-Charlson Comorbidity Index score was well balanced after weighting in the pembrolizumab and nivolumab cohorts (4.2 and 4.3, respectively). During the observation period, patients in the pembrolizumab cohort had significantly lower rates of all-cause hospitalizations (RR [95% CI] 0.33 [0.09-0.80]) and cHL-related hospitalizations (RR [95% CI] 0.14 [0.02-0.37]) than those in the nivolumab cohort. Rates of all-cause and cHL-related outpatient visits were not statistically different between patients in the pembrolizumab and nivolumab cohorts. CONCLUSIONS: In this real-world study, adult cHL patients initiated on pembrolizumab had significantly lower rates of all-cause and cHL-related hospitalizations compared to patients initiated on nivolumab.

KEYNOTE-013 4-year follow-up of pembrolizumab in classical Hodgkin lymphoma after brentuximab vedotin failure.

The KEYNOTE-013 study was conducted to evaluate pembrolizumab monotherapy in hematologic malignancies; classical Hodgkin lymphoma (cHL) was an independent expansion cohort. We present long-term results based on >4 years of median follow-up for the cHL cohort. The trial enrolled cHL patients who experienced relapse after, were ineligible for, or declined autologous stem cell transplantation and experienced progression with or did not respond to brentuximab vedotin. Patients received IV pembrolizumab 10 mg/kg every 2 weeks for up to 2 years or until confirmed progression or unacceptable toxicity. Primary end points were safety and complete response (CR) rate by central review. Enrolled patients (N = 31) had received a median of 5 therapies (range, 2 to 15). After a median follow-up of 52.8 months (range, 7.0 to 57.6 months), CR rate was 19%, and median duration of response (DOR) was not reached; 24-month and 36-month DOR rates were both 50% by the Kaplan-Meier method. Median overall survival was not reached; 36-month overall survival was 81%. Six patients (19%) experienced grade 3 treatment-related adverse events (AEs); there were no grade 4 or 5 treatment-related AEs. With long-term follow-up among a heavily pretreated cohort, pembrolizumab had a favorable safety profile; some patients maintained long-term response with pembrolizumab years after end of treatment. This trial was registered at www.clinicaltrials.gov as #NCT01953692.

Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087.

Programmed death-1 inhibitors are approved for patients with relapsed or refractory classic Hodgkin lymphoma (RRcHL). We present the 2-year follow-up of the phase 2 KEYNOTE-087 study of pembrolizumab in 210 patients, based on HL progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV; cohort 1); salvage chemotherapy and BV, with ineligibility for SCT owing to chemorefractory disease (cohort 2); and progression after SCT without BV (cohort 3). With a median follow-up of 27.6 months, the objective response rate (ORR) by blinded independent central review was 71.9% (95% CI, 65.3-77.9), the complete response rate (CRR) was 27.6%, and the partial response (PR) rate was 44.3%. Median duration of response was 16.5 months (range, 0.0+ to 27.0+ [+, no progressive disease at last assessment]) in all patients, 22.1 months in cohort 1, 11.1 months in cohort 2, and 24.4 months in cohort 3. Median progression-free survival was not reached in all patients with CR: 13.8 months (95% CI, 12.0-22.1) for patients with PR and 10.9 months (95% CI, 5.6-11.1) for patients with stable disease. Median overall survival was not reached in all patients or in any cohort. Treatment-related adverse events (TRAEs) of any grade occurred in 153 (72.9%) patients; grades 3 and 4 occurred in 25 (12.0%) patients; none resulted in death. Results confirmed effective antitumor activity, durability of response, and manageable safety of pembrolizumab monotherapy in RRcHL, regardless of prior treatment and including chemoresistant cHL. This trial was registered at www.clinicaltrials.gov as #NCT02453594.

Simultaneous Presentation of Wilms Tumor and Immature Ovarian Teratoma in Beckwith-Wiedemann Syndrome.

The Beckwith-Wiedemann syndrome is a cancer predisposition syndrome characterized by a predilection to embryonal tumor growth, especially Wilms tumor, adrenocortical carcinomas, and hepatoblastomas. Genetic analysis of patients has revealed a link to the imprinted domain of the 11p15.5 chromosome and methylation status of the H19 locus and Igf-2. These genes have also been studied in other cancers, including ovarian teratomas. Our case is a patient with a simultaneous presentation of a Wilms tumor and immature ovarian teratoma and subsequently diagnosed with Beckwith-Wiedemann syndrome, which has not been previously described.

Plasma homocysteine levels, methylene tetrahydrofolate reductase polymorphisms, and the risk of thromboembolism in children.

INTRODUCTION: Hyperhomocystenemia (HHcy) is a risk factor for thrombosis in adults. Polymorphisms in methylene tetrahydrofolate reductase (MTHFR) enzyme may cause HHcy. Data on their role in pediatric thromboembolism (TE) are sparse. MATERIALS AND METHODS: Charts of patients from 1989 to 2007, with documented TE, were reviewed. Homocysteine (Hcy) levels were defined both as per the adult normal range and the age-specific normal ranges from literature. RESULTS: A total of 141 patients (67 females, 74 males) were identified. With age-specific normal ranges for Hcy, 15 patients were found to have HHcy: 6 had CT, 9 patients had CC, and none had TT MTHFR genotype. When adult normal range was used, HHcy (>12 µmol/L) was seen in 7 patients: 4 had CT and 3 had the CC genotype. Again, none had TT genotype. In addition, the mean Hcy levels were unaffected by sex and ethnicities, but universal folic acid supplementation (post 1996) lowered the mean. CONCLUSIONS: (1) Age-specific ranges for Hcy should be used in pediatrics for accurate diagnosis of HHcy. (2) MTHFR C677T polymorphism is not a risk factor in pediatric TE. (3) Folic acid supplementation could play a role in lowering the prevalence of HHcy.