Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201).

ABSTRACT:

Background

Nearly all anti-PD-1 antibodies are of the IgG4 isotype, and thus possess residual FcR effector functions. Such anti-PD-1 antibodies are also associated with immune tolerance and escape due to instability of the CH3 domain and Fc-Fc interaction. In this trial, we examined the efficacy and safety of penpulimab, a novel IgG1 anti-PD-1 antibody that does not bind to the Fc receptor, in patients with refractory or relapsed classical Hodgkin lymphoma (R/R cHL).

Methods

Adult patients (≥18 years of age) with R/R cHL received 200 mg penpulimab once biweekly until disease progression or unacceptable toxicities for a maximum of 24 months. The primary endpoint was objective response rate (ORR) based on the Independent Radiology Review Committee per Lugano 2014 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs).

Results

A total of 94 patients were enrolled. The median follow-up was 15.8 months. The ORR was 89.4% (95% CI 80.8%, 95.0%) in the full analysis set (85 patients). Forty (47.1%) patients achieved complete remission, 36 (42.4%) patients achieved partial remission. The 12-month PFS rate was 72.1% (95% CI 60.5%, 80.8%) and the 18-month OS rate was 100%. Totally 97.9% (92/94) of patients experienced at least one TRAE. The rate of grade 3 and above TRAEs was 26.6% (25/94). In addition, 51 (54.3%) patients experienced an irAE, and 4 (4.3%) patients developed grade 3 or above irAEs. No irAE-related death occurred.

Conclusions

Penpulimab was effective and safe in patients with R/R cHL.

SUBMITTER: Song Y

PROVIDER: S-EPMC9301139 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Checkpoint Inhibitors in Relapsed/Refractory Classical Hodgkin Lymphoma.

Project description:Even though classical Hodgkin lymphoma is highly curable, the outcome of patients with a refractory or relapsed disease has been disappointing. Multiple lines of therapy are available for patients after their first failure, and most respond to subsequent therapies. However, there is a sizable proportion that remains relapsing/recurrent even after several lines of therapy. The overall prognosis of patients with relapsing and recurrent classical Hodgkin lymphoma (rrcHL) has been very disappointing until recently. Immune checkpoint inhibitors such as the anti-programmed death 1 (PD-1) receptor antibodies have recently been approved to treat relapsed and refractory cHL and have significantly improved the outcome of patients with rrcHL. The approved immune checkpoint inhibitors for relapsed and refractory cHL are nivolumab and pembrolizumab. In the Checkmate 205 study nivolumab demonstrated an objective response rate of 69% with an acceptable safety profile. Similarly, pembrolizumab demonstrated an overall response rate (ORR) of 69% with a complete remission rate (CRR) of 22.4% in the KEYNOTE-087 study in heavily pretreated patients with rrcHL.

| S-EPMC8297052 | biostudies-literature

A phase 2 multicenter study of lenalidomide in relapsed or refractory classical Hodgkin lymphoma.

Project description:Relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) remains a clinical challenge, with limited effective treatment options available after stem cell transplantation. In a multicenter phase 2 study, the efficacy of lenalidomide in rel/ref cHL patients was evaluated at a dose of 25 mg/d on days 1-21 of a 28-day cycle. Patients remained on lenalidomide until disease progression or an unacceptable adverse event (AE) occurred. Thirty-eight cHL patients were enrolled with a median of 4 (range, 2-9) prior therapies; 87% had undergone prior stem cell transplantation and 55% of patients did not respond to their last prior therapy. Of 36 evaluable patients, responses were 1 complete remission (CR), 6 partial remissions (PRs), and 5 patients with stable disease (SD) for ≥ 6 months resulting in an International Working Committee (IWC) objective overall response rate (ORR) of 19% and a cytostatic ORR of 33%. Decreased chemokine (CCL17 and CCL22) plasma levels at 2 weeks were associated with a subsequent response. The treatment was well tolerated, and the most common grade 3/4 AEs were neutropenia (47%), anemia (29%), and thrombocytopenia (18%). Four patients discontinued lenalidomide because of rash, elevated transaminases/bilirubin, and cytopenias. We provide preliminary evidence of lenalidomide's activity in patients with rel/ref cHL, and therefore exploration of lenalidomide in combination with other active agents is warranted. This trial is registered at www.ClinicalTrials.gov as NCT00540007.

| S-EPMC3217400 | biostudies-literature

Therapeutic Updates for Relapsed and Refractory Classical Hodgkin Lymphoma.

Project description:Hodgkin lymphoma (HL) is a B-cell malignancy representing approximately one in ten lymphomas diagnosed in the United States annually. The majority of patients with HL can be cured with chemotherapy; however, 5-10% will have refractory disease to front-line therapy and 10-30% will relapse. For those with relapsed or refractory (r/r) HL, salvage chemotherapy followed by autologous stem cell transplant (ASCT) is standard of care, but half of patients will subsequently have disease progression. Relapse following ASCT has been associated with exceedingly poor prognosis with a median survival of only 26 months. However, in recent years, novel agents including brentuximab vedotin (BV) and programmed cell death protein 1 monoclonal antibodies (anti-PD-1, nivolumab and pembrolizumab) have been shown to extend overall survival in r/r HL. With the success of novel agents in relapsed disease after ASCT, these therapies are beginning to show clinically meaningful response rates prior to ASCT. Finally, a new investigation in r/r HL continues to produce promising treatment options even after ASCT including CD30 directed chimeric antigen receptor T-cell therapy. In this review, we will discuss the recent advances of BV and anti-PD-1 therapy prior to ASCT, novel approaches in r/r HL after ASCT, and review active clinical trials.

| S-EPMC7601361 | biostudies-literature

Treatment of relapsed or refractory classical Hodgkin lymphoma with the anti-PD-1, tislelizumab: results of a phase 2, single-arm, multicenter study.

Project description:Prognosis is poor for patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) after failure of or who are ineligible for autologous stem cell transplant. We evaluated the efficacy and safety of tislelizumab, an investigational anti-PD-1 monoclonal antibody, in phase 2, single-arm study in Chinese patients with R/R cHL. The primary endpoint was overall response rate as assessed by an independent review committee, according to the Lugano 2014 Classification. Seventy patients were enrolled in the study and received at least one dose of tislelizumab. After median follow-up of 9.8 months, 61 (87.1%) patients achieved an objective response, with 44 (62.9%) achieving a complete response (CR). The estimated 9-month progression-free survival rate was 74.5%. Most common grade ≥3 adverse events (AEs) were upper respiratory tract infection and pneumonitis. Infusion-related reactions occurred in 27 (38.6%) patients, and 27 patients (38.6%) experienced an immune-related AE, the most common of which was thyroid dysfunction. Eleven (15.7%) patients experienced at least one treatment-emergent AE leading to dose interruption or delay. No deaths occurred due to AEs. Treatment of patients with R/R cHL with tislelizumab was generally well tolerated and resulted in high overall response and CR rates, potentially translating into more durable responses for these patients.

| S-EPMC7214259 | biostudies-literature

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

Project description: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.

| S-EPMC9344040 | biostudies-literature

Management of relapsed/refractory classical Hodgkin lymphoma in transplant-ineligible patients.

Project description:Addition of brentuximab vedotin, a CD30-targeted antibody-drug conjugate, and the programmed death 1 (PD-1) inhibitors nivolumab and pembrolizumab to the armamentarium for transplant-ineligible relapsed/refractory classical Hodgkin lymphoma has resulted in improved outcomes, including the potential for cure in a small minority of patients. For patients who have failed prior transplant or are unsuitable for dose-intense approaches based on age or comorbidities, an individualized approach with sequential use of single agents such as brentuximab vedotin, PD-1 inhibitors, everolimus, lenalidomide, or conventional agents such as gemcitabine or vinorelbine may result in prolonged survival with a minimal or modest effect on quality of life. Participation in clinical trials evaluating new approaches such as combination immune checkpoint inhibition, novel antibody-drug conjugates, or cellular therapies such as Epstein-Barr virus-directed cytotoxic T lymphocytes and chimeric antigen receptor T cells offer additional options for eligible patients.

| S-EPMC6536701 | biostudies-literature

Phase 2 study of everolimus for relapsed or refractory classical Hodgkin lymphoma.

Project description:Background:The current standard of care for classical Hodgkin lymphoma (HL) is multiagent chemotherapy with or without radiation. In patients who relapse or fail to respond, additional high-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT) can improve progression-free survival (PFS). Novel therapies are required for patients refractory to chemotherapy and AHSCT. The mammalian target of rapamycin inhibitor everolimus has shown preliminary activity in preclinical models of HL and promising efficacy in patients with relapsed or refractory HL. Methods:This was an open-label, two-stage, phase 2 study that enrolled 57 patients aged ??18 years with classic HL that had progressed after standard therapy. Patients received everolimus 10 mg daily until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision. The primary endpoint was overall response rate; secondary endpoints included PFS, overall survival, time to response, duration of response, and safety. Results:Overall response rate was 45.6% (95% confidence interval [CI] 32.4-59.3%); five patients (8.8%) experienced a complete response and 21 patients had a partial response (36.8%). Median PFS was 8.0 months (95% CI 5.1-11.0 months). Seven patients (12%) were long-term responders (??12 months). The most common study drug-related adverse events were thrombocytopenia (45.6%), fatigue (31.6%), anemia (26.3%), rash (24.6%), and stomatitis (22.8%). Conclusions:Everolimus 10 mg/day demonstrated favorable results in patients with heavily pretreated, relapsed, or refractory classical HL. These findings support the further evaluation of everolimus in this indication.Trial registration ClinicalTrials.gov NCT01022996. Registered November 25, 2009.

| S-EPMC5948762 | biostudies-literature

Five-year results of the BEGEV salvage regimen in relapsed/refractory classical Hodgkin lymphoma.

Project description:The complete remission (CR) rate achieved with induction chemotherapy prior to autologous stem cell transplantation (ASCT) represents the strongest prognostic factor in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). By inducing a CR rate of 75%, the bendamustine, gemcitabine, vinorelbine (BEGEV) regimen represents an optimal chemotherapy regimen prior to ASCT. Presented here are the 5-year results of BEGEV followed by ASCT in R/R cHL. With a median follow-up of 5 years, progression-free survival (PFS) and overall survival (OS) for the whole series (n = 59) were 59% and 78%, respectively. ASCT was performed in 43 of 49 responding patients (73% by intention to treat [ITT]; 88% by response to BEGEV) and resulted in 33 with continuous CR (56% by ITT; 77% of transplanted patients), 7 with disease relapse, and 3 with nonrelapse mortality. For patients who received transplants, the 5-year PFS and OS were 77% and 91%, respectively, with no significant difference between relapsed and refractory patients. No patient experienced secondary leukemia or myelodysplasia. In summary, the long-term efficacy data, the benefits for both relapsed and refractory patients, and the excellent safety profile provide a strong rationale for further development of the BEGEV regimen. This trial was registered at EudraCT as #2010-022169-91 and at www.clinicaltrials.gov as #NCT01884441.

| S-EPMC6960479 | biostudies-literature

Transplant strategies in relapsed/refractory Hodgkin lymphoma.

Project description:The majority of patients with Hodgkin lymphoma (HL) are cured with initial therapy. However, high-dose therapy with autologous hematopoietic cell transplant (AHCT) allows for the cure of an additional portion of patients with relapsed or primary refractory disease. Positron emission tomography-negative complete remission before AHCT is critical for long-term disease control. Several salvage options are available with comparable response rates, and the choice can be dependent of comorbidities and logistics. Radiation therapy can also improve the remission rate and is an important therapeutic option for selected patients. Brentuximab vedotin (BV) maintenance after AHCT is beneficial in patients at high risk for relapse, especially those with more than 1 risk factor, but can have the possibility of significant side effects, primarily neuropathy. Newer agents with novel mechanisms of action are under investigation to improve response rates for patients with subsequent relapse, although are not curative alone. BV and the checkpoint inhibitors nivolumab and pembrolizumab are very effective with limited side effects and can bridge patients to curative allogeneic transplants (allo-HCT). Consideration for immune-mediated toxicities, timing of allogeneic hematopoietic cell transplant based on response, and the potential for increased graft-versus-host disease remain important. Overall, prospective investigations continue to improve outcomes and minimize toxicity for relapsed or primary refractory HL patients.

| S-EPMC5897866 | biostudies-literature

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.

| S-EPMC8791579 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data