ABVD plus rituximab versus ABVD alone for advanced stage, high-risk classical Hodgkin lymphoma: a randomized phase 2 study.
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ABSTRACT:
SUBMITTER: Strati P
PROVIDER: S-EPMC6355491 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
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ABVD plus rituximab <i>versus</i> ABVD alone for advanced stage, high-risk classical Hodgkin lymphoma: a randomized phase 2 study.
Strati Paolo P Fanale Michelle A MA Oki Yasuhiro Y Turturro Francesco F Fayad Luis E LE Bartlett Nancy L NL Gladstone Douglas E DE Kasamon Yvette L YL Portlock Carol S CS Wilson Wyndham H WH Goy Andre A Younes Anas A Lee Hun Ju HJ
Haematologica 20180906 2
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Project description:In the present study, we evaluated the efficacy and safety of rituximab in combination with standard doxorubicin, bleomycin, vinblastine, and dacarbazine (RABVD) in patients with classical Hodgkin lymphoma (cHL). In this phase 2 study, patients with chemotherapy-naive, advanced-stage cHL were treated with rituximab 375 mg/m(2) weekly for 6 weeks and standard ABVD for 6 cycles. The primary outcome was event-free survival (EFS) at 5 years. Eighty-five patients were enrolled, of whom 78 were eligible. With a median follow-up duration of 68 months (range, 26-110), and based on an intent-to-treat analysis, the 5-year EFS and overall survival rates were 83% and 96%, respectively. The 5-year EFS for patients with stage III/IV cHL was 82%. Furthermore, the 5-year EFS for patients with an International Prognostic Score of 0-2 was 88% and for those with a score of > 2, it was 73%. The most frequent treatment-related grade 3 or 4 adverse events were neutropenia (23%), fatigue (9%), and nausea (8%). Our results demonstrate that the addition of rituximab to ABVD is safe and has a promising clinical activity in patients with advanced-stage cHL. These data are currently being confirmed in a multicenter randomized trial.
| S-EPMC3359733 | biostudies-literature
Project description:In classical Hodgkin lymphoma, circulating clonotypic malignant cells express CD20, which potentially explains the observed activity of rituximab. This multicenter phase 2 study investigated the combination of rituximab-ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for stage II-IV untreated classical Hodgkin lymphoma. A goal was to assess the behavior of circulating clonotypic B cells clinically. Of 49 evaluable patients, 69% had stage IIB-IV disease; 8% had CD20(+) Hodgkin and Reed-Sternberg cells. Rituximab-ABVD was generally well tolerated. Delivered relative dose intensity was 94% for AVD and 79% for bleomycin. After 6 cycles, 81% of patients were in complete remission. Only 8% received radiation therapy. The actuarial 3-year event-free and overall survival rates were 83% and 98%, respectively. EBV copy number in plasma fell dramatically during cycle 1 in patients with EBV(+) tumors. Persistence of detectable circulating clonotypic B cells was associated with a greater relapse frequency (P < .05). Rituximab-ABVD and clonotypic B cells warrant additional study in classical Hodgkin lymphoma.
| S-EPMC3359734 | biostudies-literature
Project description:BackgroundChemotherapy plus radiation treatment is effective in controlling stage IA or IIA nonbulky Hodgkin's lymphoma in 90% of patients but is associated with late treatment-related deaths. Chemotherapy alone may improve survival because it is associated with fewer late deaths.MethodsWe randomly assigned 405 patients with previously untreated stage IA or IIA nonbulky Hodgkin's lymphoma to treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or to treatment with subtotal nodal radiation therapy, with or without ABVD therapy. Patients in the ABVD-only group, both those with a favorable risk profile and those with an unfavorable risk profile, received four to six cycles of ABVD. Among those assigned to subtotal nodal radiation therapy, patients who had a favorable risk profile received subtotal nodal radiation therapy alone and patients with an unfavorable risk profile received two cycles of ABVD plus subtotal nodal radiation therapy. The primary end point was 12-year overall survival.ResultsThe median length of follow-up was 11.3 years. At 12 years, the rate of overall survival was 94% among those receiving ABVD alone, as compared with 87% among those receiving subtotal nodal radiation therapy (hazard ratio for death with ABVD alone, 0.50; 95% confidence interval [CI], 0.25 to 0.99; P=0.04); the rates of freedom from disease progression were 87% and 92% in the two groups, respectively (hazard ratio for disease progression, 1.91; 95% CI, 0.99 to 3.69; P=0.05); and the rates of event-free survival were 85% and 80%, respectively (hazard ratio for event, 0.88; 95% CI, 0.54 to 1.43; P=0.60). Among the patients randomly assigned to ABVD alone, 6 patients died from Hodgkin's lymphoma or an early treatment complication and 6 died from another cause; among those receiving radiation therapy, 4 deaths were related to Hodgkin's lymphoma or early toxic effects from the treatment and 20 were related to another cause.ConclusionsAmong patients with Hodgkin's lymphoma, ABVD therapy alone, as compared with treatment that included subtotal nodal radiation therapy, was associated with a higher rate of overall survival owing to a lower rate of death from other causes. (Funded by the Canadian Cancer Society and the National Cancer Institute; HD.6 ClinicalTrials.gov number, NCT00002561.).
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Project description:BackgroundRituximab has been shown to improve response rates and progression free survival when added to chemotherapy in patients with indolent and mantle cell lymphoma. However, the impact of R on overall survival (OS) when given in combination with chemotherapy (R-chemo) has remained unclear so far.ObjectivesWe thus performed a comprehensive systematic review in this group of patients to compare R-chemo with chemotherapy alone with respect to OS. Other endpoints were overall response rate (ORR), toxicity and disease control as assessed by measures such as time to treatment failure (TTF), event free-survival (EFS), progression free-survival (PFS) and time to progression (TTP).Search strategyWe searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and conference proceeding from 1990 to 2005.Selection criteriaOnly randomised controlled trials (RCT) comparing R-chemo with chemotherapy alone in patients with newly diagnosed or relapsed indolent lymphoma and mantle cell lymphoma (MCL) were included.Data collection and analysisTwo review authors extracted data and assessed the study quality. Number needed to treat (NNT) were calculated to facilitate interpretation.Main resultsSeven randomised controlled trials involving 1943 patients with follicular lymphoma, mantle cell lymphoma, or other indolent lymphomas were included in the meta-analysis. Five studies were published as full-text articles, and two were in abstract form. Patients treated with R-chemo had better overall survival (hazard ratio [HR] for mortality 0.65; 95% confidence interval (CI) 0.54 to 0.78), overall response (relative risk of tumour response 1.21; 95% CI 1.16 to 1.27), and disease control (HR of disease event 0.62; 95% CI 0.55 to 0.71) than patients treated with chemotherapy alone. R-chemo improved overall survival in patients with follicular lymphoma (HR for mortality 0.63; 95% CI 0.51 to 0.79) and in patients with mantle cell lymphoma (HR for mortality 0.60; 95% CI 0.37 to 0.98). However, in the latter case, there was heterogeneity among the trials (P 0.07), making the survival benefit less reliable.Authors' conclusionsThe systematic review demonstrated improved OS for patients with indolent lymphoma, particularly in the subgroups of follicular and in mantle cell lymphoma when treated with R-chemo compared to chemotherapy alone.
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Project description:ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) with or without radiation has been the standard treatment for limited-stage Hodgkin lymphoma (HL) but carries risks of bleomycin lung injury and radiation toxicity. Brentuximab vedotin (BV) is approved with AVD for stage III-IV HL, but carries increased risks of peripheral neuropathy (PN) and neutropenic fever, likely due to overlapping toxicity between BV and vinblastine. We therefore evaluated BV in combination with AD for 4 or 6 cycles based on interim positron emission tomography response. Thirty-four patients with nonbulky stage I-II HL were enrolled. Risk was early favorable in 53% and unfavorable in 47%. The overall and complete response rates (CRRs) were 100% and 97%, respectively, with a 5-year progression-free survival (PFS) of 91%. No differences in outcome were observed based on stage (I vs II) or risk status (early favorable vs unfavorable). The most common adverse events were nausea (85%), peripheral sensory neuropathy (59%), and fatigue (56%). There were no cases of grade-4 neutropenia or neutropenic fever, and no patient received granulocyte-colony stimulating factor. Most cases of PN were grade 1, and no patient experienced grade ≥3 PN. BV-AD produced a high CRR and durable PFS with most patients requiring 4 cycles of therapy. Compared with BV-AVD, the toxicity profile appeared improved, with predominantly grade 1 reversible PN and no case of grade 4 neutropenia or neutropenic fever. This regimen warrants further study in HL and may serve as a backbone for the addition of novel agents. This trial is registered on clinicaltrials.gov (NCT02505269).
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