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Objectives: Patients with classical Hodgkin lymphoma (cHL) relapsing after second‐line therapy have a dismal prognosis and novel approaches are required for this patient group. Based on promising (pre‐)clinical data and the favourable toxicity profile, we performed a phase II clinical trial with the JAK inhibitor ruxolitinib in patients with relapsed or refractory cHL (r/r cHL). Methods: Patients ≥18 years with histologically confirmed r/r cHL who failed second‐line treatment were included. Ruxolitinib was given orally at a dose of 25 mg twice daily in continuous 28‐day cycles until progression or unacceptable toxicity. Primary endpoint was the PET/CT‐based overall response rate (ORR; complete response (CR) or partial response (PR)) after 2 cycles; secondary endpoints included progression‐free (PFS) and overall survival (OS) as well as feasibility. The Jericho Trial adopted a 2‐stage phase 2 design (Simon 1989). Results: Among the 12 included patients in stage 1, 2 had a PR, 3 had a stable disease (SD) and 6 had progressive disease (PD) after two treatment cycles (ORR: 2/12 evaluable patients, 16.7%). Median PFS was 3.6 months, the 1‐year OS estimate was 50.6% (median not reached). The toxicity profile was favourable with only one grade IV adverse event (7.1%) reported. Conclusion: Ruxolitinib exhibited a favourable side effect profile but modest activity in r/r cHL. Although the formal stopping criterion after stage 1 was not met, the trial did not continue to stage 2 due to the low response and PFS rates observed in stage 1. [ABSTRACT FROM AUTHOR]

Summary: Reinduction chemotherapy followed by high‐dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second‐line standard of care for transplant‐eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high‐dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant‐eligible patients aged 18–60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase‐I‐part) was administered on day 0–13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end‐point of computed tomography (CT)‐based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT‐based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end‐point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aimed to determine the effectiveness of brentuximab vedotin (BV) in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) in the clinical practice setting using most recent results. A total of 32 observational studies reporting on treatment patterns, overall response rate (ORR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and adverse events were found. After four cycles, a random-effect model yielded pooled ORR and CR rates of 62.6% (95% confidence interval (CI): 56.0–68.9; I2 = 9.7%) and 32.9% (95% CI, 20.8–46.3, I2 = 64.8%), respectively. Regarding survival, 1-year, 2-year, and 5-year PFS ranged from 52.1% to 63.2%, 45.2% to 56.2%, and 31.9% to 33.0%, respectively. OS rates were 68.2–82.7%, 58.0–81.9%, and 58.0–62.0%, respectively. Most common adverse events were hematological toxicities (neutropenia: 13.3–23%, anemia: 8.8–39.0%, and thrombocytopenia: 4–4.6%), and grade ≥3 peripheral neuropathy (3.3–7.3%). This study supports the effectiveness and safety of BV in R/R cHL patients in the real-world setting. [ABSTRACT FROM AUTHOR]

We examined real-world data on management of relapsed/refractory Hodgkin lymphoma (R/R HL) in five European countries and the consistency of these data with guideline recommendations. Retrospective clinical and epidemiologic data for 509 patients with R/R HL treated between January 2014 and March 2015 were collected at centers in France, Germany, Italy, Spain, and the United Kingdom. Mean age was 46.3 years; 73.3% were receiving second-line therapy for a first relapse during the reporting period. Most patients received ABVD as front-line chemotherapy, except in Germany where escalated BEACOPP was used more often. The proportion of patients receiving stem cell transplantation (SCT) was 44%; 85% of transplants occurred at first relapse. Brentuximab vedotin (BV) was usually administered after autologous SCT, and was initiated for 65% of patients following SCT failure. Our findings suggest that R/R HL management across these countries is broadly consistent with guideline recommendations and that BV is well-integrated into treatment pathways. [ABSTRACT FROM AUTHOR]

The article provides information on a study which observed the link between different blood count parameters at baseline with response and progression-free survival (PFS) in relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL) patients treated with the anti-PD1 antibody, nivolumab. Topics discussed include role of eosinophils as co-effectors of the immune response, and results of the study.

Classical Hodgkin lymphoma (cHL) is the most common hematological malignancy in young adults and can be cured in most cases. However, relapsed and refractory Hodgkin lymphoma, certain patient groups, such as elderly patients, and toxicity of first-line treatment still pose significant challenges. Consequently, new treatment options are needed. Recently, many new treatment concepts have been evaluated in clinical trials. Targeted drug-antibody conjugates and immune checkpoint inhibitors have decisively changed treatment approaches. This review aims to give a comprehensive overview of novel agents in Hodgkin lymphoma that have been recently or are currently being evaluated in clinical trials. In addition to dedicated sections on brentuximab vedotin (BV) and immune checkpoint inhibitors, other emerging substances and concepts are discussed. In doing so, this review compares trial results regarding safety and efficacy. A special focus lies on the effect novel agents will have on the different treatment settings faced by clinicians involved in the treatment of Hodgkin lymphoma. [ABSTRACT FROM PUBLISHER]

Treatment for Hodgkin lymphoma is effective for about 85% of the patients. A gold-standard for the 15% of relapsing patients is still missing. High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) has shown efficacy and safety for patients, but up to date no survival benefit revealed. After systematic literature search we identified three randomised controlled trials from 1663 total hits. Meta-analysis of two trials (157 patients) showed a statistically significant increase in progression-free survival (hazard ratio 0.55, 95% confidence interval 0.35–0.86) for patients treated with HDCT and ASCT compared to conventional chemotherapy, but no difference in overall survival nor increased adverse events. The third trial (241 patients) showed an statistically significant increase in infections and 5% more treatment-related mortalities following sequential HDCT plus HDCT and ASCT compared to HDCT plus ASCT, without differences in the efficacy endpoints overall survival or progression-free survival. [ABSTRACT FROM AUTHOR]

Only limited data are available on the role of brentuximab vedotin (SGN-35) in transplant-naive relapsed or refractory patients with Hodgkin lymphoma (HL). We thus retrospectively analyzed 14 patients with primary refractory or relapsed HL who were treated with brentuximab vedotin as single agent in a named patient program, who had not received prior high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT) due to refractory disease ( n = 9), comorbidity ( n = 4) and unknown reasons ( n = 1). Brentuximab vedotin resulted in an overall response rate of 71% (10/14) with five complete responses (CRs). Five of those patients with refractory disease and four patients with relevant comorbidity responded. Consolidating ASCT ( n = 4) or allogeneic SCT ( n = 1) was performed in five patients. Median progression-free survival (PFS) was 9 months and the median overall survival (OS) was not reached. These data indicate the therapeutic efficacy of brentuximab vedotin in chemotherapy-refractory transplant-naive patients with HL. [ABSTRACT FROM AUTHOR]