P062: The efficacy and safety of nivolumab 40 mg therapy versus 3 mg/kg in patients with relapsed and refractory classic Hodgkin lymphoma
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ABSTRACT:
SUBMITTER: Fedorova L
PROVIDER: S-EPMC9621487 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC9430497 | biostudies-literature
Project description:The introduction of nivolumab has changed the landscape of relapsed/refractory classical Hodgkin lymphoma (r/r cHL) treatment. Despite its clinical importance, this therapy may remain inaccessible for a significant number of patients worldwide, especially in low-income countries, due to its high cost. The results of pharmacokinetic analysis and clinical observations suggest the potential efficacy of low dose nivolumab in r/r cHL patients. The aim of this trial was to assess the efficacy and safety of nivolumab at a fixed dose of 40 mg in patients with r/r cHL. The study included 30 patients with r/r cHL, treated with 40 mg nivolumab every 2 weeks. The median dose of nivolumab per kilogram bodyweight was 0.59 mg/kg (0.4-1 mg/kg). Median follow up was 19.2 months (range 12.7-25.4). The objective response rate was 70%, with 13 (43.3%) patients achieving a complete response. Median PFS was 18.4 months (95% CI, 11.3 to 18.5 months) with 18-month PFS of 53.6% (95% CI, 32%-71%). At the time of analysis, 96.7% of patients were alive with a median OS not reached. Severe (grade 3-5) adverse events were observed in 4 patients (13.3%). Nivolumab in a fixed dose of 40 mg was efficient in patients with r/r cHL, independent from dose per kg bodyweight. The results of this study are in good agreement with previously reported data and create a rationale for further studies aimed to define the optimal dosing regimen of nivolumab for the treatment of r/r cHL. Registered at www.clinicaltrials.gov (NCT03343665).
| S-EPMC7523758 | biostudies-literature
Project description:ObjectivesTherapy of patients with relapsed and refractory classic Hodgkin lymphoma (r/r cHL) after PD-1 inhibitors failure remains an unresolved issue. The aim of this study was to evaluate the efficacy and safety of the combination of nivolumab with brentuximab vedotin (Nivo + BV) after nivolumab monotherapy failure.MethodsThis study retrospectively analyzed 21 patients with r/r cHL who were treated with the combination of Nivo + BV after Nivo failure. The response was evaluated by PET-CT scan according to the LYRIC criteria. Adverse events (AEs) were assessed according to NCI CTCAE v.4.03.ResultsMedian follow-up was 19 (9-47) months. The ORR was 57%. The median OS was not reached, 24 month OS was 80% (95% CI 50-93%). Median PFS was 12 months with 24 month PFS of 31% (95% CI 12-53%). Any grade AEs were observed in 12 patients (63%), 3-4 grade AEs in 2 patients (10%). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after Nivo + BV was performed in 8 (38%) patients. The median time between Nivo + BV and allo-HSCT was 8 (5-21) months.ConclusionsCombination of Nivo + BV in r/r cHL after nivolumab monotherapy failure is potentially an effective and safe approach.
| S-EPMC8619646 | biostudies-literature
Project description:The checkpoint inhibitors nivolumab and pembrolizumab are principal treatment options for relapsed or refractory classic Hodgkin lymphoma. In patients who decline autologous stem-cell transplantation or who are unsuited for high-dose chemotherapy and subsequent autologous stem-cell transplantation because of comorbidities, the use of checkpoint inhibitors may improve overall survival and have a manageable side effect profile. This clinical review provides an evidence-based summary to guide practicing oncologists in the use of checkpoint inhibitors in relapsed or refractory classic Hodgkin lymphoma and includes checkpoint inhibitor efficacy and adverse effect profiles. We highlight the use of checkpoint inhibitors in the management of relapsed or refractory classic Hodgkin lymphoma in patients who are ineligible for an autologous stem-cell transplant with the goal of improving disease control while limiting adverse events.
| S-EPMC8258137 | biostudies-literature
Project description:Most patients with classic Hodgkin lymphoma (cHL) are cured with combination chemotherapy, but approximately 10-20% will relapse, and another 5-10% will have primary refractory disease. The treatment landscape of relapsed/refractory (R/R) cHL has evolved significantly over the past decade following the approval of brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, and the PD-1 inhibitors nivolumab and pembrolizumab. These agents have significantly expanded options for salvage therapy prior to autologous hematopoietic cell transplantation (AHCT), post-transplant maintenance, and treatment of relapse after AHCT, which have led to improved survival in the modern era. In this review, we highlight our approach to the management of R/R cHL in 2023 with a focus on choosing first salvage therapy, post-transplant maintenance, and treatment of relapse after AHCT. We also discuss the management of older adults and transplant-ineligible patients, who require a separate approach. Finally, we review novel immunotherapy approaches in clinical trials, including combinations of PD-1 inhibitors with other immune-activating agents as well as novel antibody-drug conjugates, bispecific antibodies, and cellular immunotherapies. Ongoing studies assessing biomarkers of response to immunotherapy and dynamic biomarkers such as circulating tumor DNA may further inform treatment decisions and enable a more personalized approach in the future.
| S-EPMC10526852 | biostudies-literature
Project description:Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response ≥ 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.
| S-EPMC5791843 | biostudies-literature
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
Project description:In this phase 1/2 study, brentuximab vedotin (BV) and nivolumab (Nivo) administered in combination were evaluated as initial salvage therapy in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL). Patients received up to 4 cycles of combination treatment, with BV administered on day 1 and Nivo on day 8 of the first cycle. For cycles 2 to 4, BV and Nivo were both administered on day 1. After study treatment, responses were evaluated by investigators per the 2014 Lugano classification, and patients could proceed to autologous stem cell transplantation (ASCT). Sixty-two patients were enrolled; the complete response rate among all treated patients (n = 61) was 61%, with an objective response rate of 82%. Before ASCT, adverse events (AEs) occurred in 98% of patients, mostly grades 1 and 2. Infusion-related reactions (IRRs) occurred in 44% of patients overall, with 41% of patients experiencing an IRR during at least 1 infusion of BV. Five patients (8%) were treated with systemic steroids for immune-related AEs. A reduction of peripheral T-cell subsets including regulatory T cells was observed after the first dose of BV, and reduced serum levels of thymus- and activation-regulated chemokine concurrent with an increase in proinflammatory cytokines and chemokines were seen after the first BV plus Nivo infusions. The combination of BV plus Nivo was an active and well-tolerated first salvage regimen, potentially providing patients with R/R HL an alternative to traditional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT02572167.
| S-EPMC5855021 | biostudies-literature
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
Project description:Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)-naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C). All patients received nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary end point was objective response rate per independent radiology review committee. Results Overall, 243 patients were treated; 63 in cohort A, 80 in cohort B, and 100 in cohort C. After a median follow-up of 18 months, 40% continued to receive treatment. The objective response rate was 69% (95% CI, 63% to 75%) overall and 65% to 73% in each cohort. Overall, the median duration of response was 16.6 months (95% CI, 13.2 to 20.3 months), and median progression-free survival was 14.7 months (95% CI, 11.3 to 18.5 months). Of 70 patients treated past conventional disease progression, 61% of those evaluable had stable or further reduced target tumor burdens. The most common grade 3 to 4 drug-related adverse events were lipase increases (5%), neutropenia (3%), and ALT increases (3%). Twenty-nine deaths occurred; none were considered treatment related. Conclusion With extended follow-up, responses to nivolumab were frequent and durable. Nivolumab seems to be associated with a favorable safety profile and long-term benefits across a broad spectrum of patients with relapsed/refractory cHL.
| S-EPMC6075855 | biostudies-literature