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Novel Agents For Relapsed and Refractory Classical Hodgkin Lymphoma: A Review.

ABSTRACT: Classical Hodgkin lymphoma (cHL) is the most common type of HL that occurs mainly in people aged between 15-30 and over 55 years. Although its general prognosis is favorable, 10%-30% of patients with cHL will ultimately develop relapsed or refractory disease (r/r cHL). Improving the cure rate of r/r cHL has proven to be challenging. Some novel agents, such as brentuximab vedotin and immune checkpoint inhibitors, which have been used in conventional regimens for patients with r/r cHL in the past decade, have been shown to have good curative effects. This paper reviews the conventional regimens for patients with r/r cHL and focuses on the newest clinical trials and treatment measures to prolong prognosis and reduce adverse events. The evaluation of prognosis plays a vital role in analyzing the risk of relapse or disease progression; thus, finding new predictive strategies may help treat patients with r/r cHL more efficaciously.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9344040 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Novel Agents For Relapsed and Refractory Classical Hodgkin Lymphoma: A Review.

Zhang Yujie Y Xing Zhichao Z Mi Li L Li Zhihui Z Zhu Jingqiang J Wei Tao T Wu Wenshuang W

Frontiers in oncology 20220714

Classical Hodgkin lymphoma (cHL) is the most common type of HL that occurs mainly in people aged between 15-30 and over 55 years. Although its general prognosis is favorable, 10%-30% of patients with cHL will ultimately develop relapsed or refractory disease (r/r cHL). Improving the cure rate of r/r cHL has proven to be challenging. Some novel agents, such as brentuximab vedotin and immune checkpoint inhibitors, which have been used in conventional regimens for patients with r/r cHL in the past ...[more]

PMID: 35928877

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

Project description: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.

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Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma.

Project description:Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received pembrolizumab for ≤2 years. Patients in CR who discontinued treatment and subsequently experienced PD were eligible for second-course pembrolizumab. Primary end points were the objective response rate (ORR) using blinded central review and safety. The median follow-up was 63.7 months. ORR was 71.4% (95% confidence interval [CI], 64.8-77.4; CR, 27.6%; partial response, 43.8%). Median duration of response (DOR) was 16.6 months; median progression-free survival was 13.7 months. A quarter of responders, including half of complete responders, maintained a response for ≥4 years. Median overall survival was not achieved. Among 20 patients receiving second-course pembrolizumab, ORR for 19 evaluable patients was 73.7% (95% CI, 48.8-90.8); median DOR was 15.2 months. Any-grade treatment-related adverse events occurred in 72.9% of patients and grade 3 or 4 adverse events occurred in 12.9% of patients; no treatment-related deaths occurred. Single-agent pembrolizumab can induce durable responses, particularly in patients achieving CR. Second-course pembrolizumab frequently reinduced sustained responses after relapse from initial CR.

| S-EPMC10624931 | biostudies-literature

Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis.

Project description:PurposeTislelizumab is an anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody specifically designed to minimize binding to Fcγ receptors (FcγR).Patients and methodsHere, we present the extended 3-year follow-up of a phase II study of tislelizumab in 70 patients with relapsed/refractory classical Hodgkin lymphoma (cHL) who failed or were ineligible for autologous stem cell transplantation.ResultsWith a median follow-up of 33.8 months, the overall response rate by the independent review committee was 87.1%, and the complete response (CR) rate was 67.1%. Responses were durable as shown by a median duration of response of 31.3 months, and median progression-free survival (PFS) of 31.5 months. The 3-year PFS and overall survival rates were 40.8% and 84.8%, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 97.1% of patients; the grade ≥3 TRAE rate was low (31.4%), and only 8.6% of patients experienced adverse events leading to treatment discontinuation. Correlative biomarker analysis showed that FcγRΙ-expressing macrophages had no observed impact on either the CR rate or PFS achieved with tislelizumab, which may be potentially related to its engineered Fc region.ConclusionsWith extended follow-up, tislelizumab yielded long-term benefits and demonstrated a favorable safety profile for patients with relapsed/refractory cHL. This trial was registered at clinicaltrials.gov as NCT03209973.

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Avelumab in relapsed/refractory classical Hodgkin lymphoma: phase 1b results from the JAVELIN Hodgkins trial.

Project description:The 9p24.1 chromosomal alteration in classical Hodgkin lymphoma (cHL) is associated with increased expression of programmed death ligand 1 (PD-L1)/PD-L2 and an immunosuppressive tumor microenvironment. Blockade of PD-L1/PD-1 interactions with avelumab (anti-PD-L1) is hypothesized to restore antitumor immunity. JAVELIN Hodgkins was a phase 1b, multiple-dose, open-label, randomized, parallel-arm trial of avelumab in patients with relapsed/refractory (R/R) cHL. Primary end points included avelumab target occupancy by dose/schedule in peripheral blood immune cells and pharmacokinetic parameters. Secondary end points included safety and antitumor activity. Four dose levels and 2 dosing schedules were investigated: 70, 350, and 500 mg administered every 2 weeks; 500 mg every 3 weeks; and 10 mg/kg every 2 weeks. Thirty-one patients with R/R cHL were randomized; 9 (29.0%) and 20 (64.5%) had received 3 or ≥4 prior anticancer treatments, respectively. Target occupancy of >90% was observed across all treatment arms, throughout the dosing interval. Avelumab pharmacokinetic data were similar to those previously reported. The most common treatment-related adverse events of any grade were infusion-related reaction (30.0%), nausea (20.0%), increased alanine aminotransferase and rash (16.7% each), and fatigue (13.3%). The objective response rate (ORR) in all randomized patients was 41.9%, with a complete response rate of 19.4%; ORR in those with prior allogeneic hematopoietic stem cell transplant (allo-HSCT) was 55.6%. Due to decreased use of allo-HSCT in patients with R/R cHL, the expansion phase enrolling post-allo-HSCT patients was terminated. Avelumab was tolerable and demonstrated antitumor activity in heavily pretreated patients with cHL, suggesting that PD-L1 blockade may be sufficient for therapeutic benefit in cHL. This trial was registered at www.clinicaltrials.gov as #NCT02603419.

| S-EPMC8525219 | biostudies-literature

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