PET-guided eBEACOPP treatment of advanced-stage Hodgkin lymphoma (HD18): follow-up analysis of an international, open-label, randomised, phase 3 trial

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F21%3A43921587" target="_blank" >RIV/00216208:11120/21:43921587 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064173:_____/21:N0000227

Výsledek na webu

<a href="https://doi.org/10.1016/S2352-3026(21)00101-0" target="_blank" >https://doi.org/10.1016/S2352-3026(21)00101-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S2352-3026(21)00101-0" target="_blank" >10.1016/S2352-3026(21)00101-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

PET-guided eBEACOPP treatment of advanced-stage Hodgkin lymphoma (HD18): follow-up analysis of an international, open-label, randomised, phase 3 trial

Popis výsledku v původním jazyce

BACKGROUND: The German Hodgkin Study Group&apos;s HD18 trial established the safety and efficacy of PET-guided eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) for the treatment of advanced-stage Hodgkin lymphoma. However, because of a protocol amendment during the enrolment period (June 1, 2011) that changed standard treatment from eight to six cycles, the results of the HD18 trial have been partially immature. We report a prespecified 5-year follow-up analysis of the completed HD18 trial. METHODS: HD18 was an international, open-label, randomised, phase 3 trial done in 301 hospitals and private practices in five European countries. Patients aged 18-60 years with newly diagnosed, advanced-stage Hodgkin lymphoma and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited. After receiving an initial two cycles of eBEACOPP (1250 mg/m(2) intravenous cyclophosphamide [day 1], 35 mg/m(2) intravenous doxorubicin [day 1], 200 mg/m(2) intravenous etoposide [day 1-3], 100 mg/m(2) oral procarbazine [day 1-7], 40 mg/m(2) oral prednisone [day 1-14], 1.4 mg/m(2) intravenous vincristine [day 8], and 10 mg/m(2) intravenous bleomycin [day 8]), patients underwent a contrast-enhanced CT and PET scan (PET-2). Patients with positive PET-2 were randomly assigned to receive standard therapy (an additional six cycles of eBEACOPP; ie, eight cycles in total) or experimental therapy (an additional six cycles of eBEACOPP plus 375 mg/m(2) intravenous rituximab; ie, eight cycles in total) until June 1, 2011. After June 1, 2011, all patients with positive PET-2 were assigned to the updated standard therapy with an additional four cycles of eBEACOPP (ie, six cycles in total). Patients with negative PET-2 were randomly assigned (1:1) to receive standard therapy (an additional six cycles of eBEACOPP [ie, eight cycles in total] until June 1, 2011; an additional four cycles of eBEACOPP [ie, six cycles in total] after June 1, 2011) or experimental therapy (an additional two cycles of eBEACOPP; ie, four cycles in total). Randomisation was done centrally with the minimisation method, including a random component, stratified by centre, age, stage, international prognostic score, and sex. The primary endpoint was progression-free survival. HD18 aimed to improve 5-year progression-free survival by 15% in the PET-2-positive intention-to-treat cohort and to exclude inferiority of 6% or more in 5-year progression-free survival in the PET-2-negative per-protocol population. This study is registered with ClinicalTrials.gov, NCT00515554, and is completed. FINDINGS: Between May 14, 2008, and July 18, 2014, 2101 patients were enrolled and 1945 were assigned to a treatment group according to their PET-2 result. In the PET-2-positive cohort, with a median follow-up of 73 months (IQR 59 to 94), 5-year progression-free survival was 89.9% (95% CI 85.7 to 94.1) in 217 patients assigned to eight cycles of eBEACOPP before the protocol amendment and 87.7% (83.1 to 92.4) in 217 patients assigned to eight cycles of rituximab plus eBEACOPP (p=0.40). Among 506 patients who received six cycles of eBEACOPP after the protocol amendment, 5-year progression-free survival was 90.1% (95% CI 87.2 to 92.9), with a median follow-up of 58 months (IQR 39 to 66). In the PET-2-negative cohort, with a median follow-up of 66 months (IQR 54 to 85) in the combined pre-amendment and post-amendment groups, 5-year progression-free survival was 91.2% (95% CI 88.4 to 93.9) in 446 patients who received eight or six cycles of eBEACOPP and 93.0% (90.6 to 95.4) in 474 patients who received four cycles of eBEACOPP (difference 1.9% [95% CI -1.8 to 5.5]). In the subgroup of PET-2-negative patients randomly assigned after protocol amendment, 5-year progression-free survival was 90.9% (95% CI 86.8 to 95.1) in 202 patients assigned to receive six cycles of eBEACOPP and 91.0% (86.6 to 95.5) in 200 patients assigned to receive four cycles of eBEACOPP (difference 0.1% [-5.9 to 6.2]). INTERPRETATION: Long-term follow-up confirms the efficacy and safety of PET-2-guided eBEACOPP in patients with advanced-stage Hodgkin lymphoma. The reduction from eight to four cycles of eBEACOPP represents a benchmark in the treatment of early-responding patients, who can now be potentially cured with a short and safe treatment approach.

Název v anglickém jazyce

PET-guided eBEACOPP treatment of advanced-stage Hodgkin lymphoma (HD18): follow-up analysis of an international, open-label, randomised, phase 3 trial

Popis výsledku anglicky

BACKGROUND: The German Hodgkin Study Group&apos;s HD18 trial established the safety and efficacy of PET-guided eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) for the treatment of advanced-stage Hodgkin lymphoma. However, because of a protocol amendment during the enrolment period (June 1, 2011) that changed standard treatment from eight to six cycles, the results of the HD18 trial have been partially immature. We report a prespecified 5-year follow-up analysis of the completed HD18 trial. METHODS: HD18 was an international, open-label, randomised, phase 3 trial done in 301 hospitals and private practices in five European countries. Patients aged 18-60 years with newly diagnosed, advanced-stage Hodgkin lymphoma and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited. After receiving an initial two cycles of eBEACOPP (1250 mg/m(2) intravenous cyclophosphamide [day 1], 35 mg/m(2) intravenous doxorubicin [day 1], 200 mg/m(2) intravenous etoposide [day 1-3], 100 mg/m(2) oral procarbazine [day 1-7], 40 mg/m(2) oral prednisone [day 1-14], 1.4 mg/m(2) intravenous vincristine [day 8], and 10 mg/m(2) intravenous bleomycin [day 8]), patients underwent a contrast-enhanced CT and PET scan (PET-2). Patients with positive PET-2 were randomly assigned to receive standard therapy (an additional six cycles of eBEACOPP; ie, eight cycles in total) or experimental therapy (an additional six cycles of eBEACOPP plus 375 mg/m(2) intravenous rituximab; ie, eight cycles in total) until June 1, 2011. After June 1, 2011, all patients with positive PET-2 were assigned to the updated standard therapy with an additional four cycles of eBEACOPP (ie, six cycles in total). Patients with negative PET-2 were randomly assigned (1:1) to receive standard therapy (an additional six cycles of eBEACOPP [ie, eight cycles in total] until June 1, 2011; an additional four cycles of eBEACOPP [ie, six cycles in total] after June 1, 2011) or experimental therapy (an additional two cycles of eBEACOPP; ie, four cycles in total). Randomisation was done centrally with the minimisation method, including a random component, stratified by centre, age, stage, international prognostic score, and sex. The primary endpoint was progression-free survival. HD18 aimed to improve 5-year progression-free survival by 15% in the PET-2-positive intention-to-treat cohort and to exclude inferiority of 6% or more in 5-year progression-free survival in the PET-2-negative per-protocol population. This study is registered with ClinicalTrials.gov, NCT00515554, and is completed. FINDINGS: Between May 14, 2008, and July 18, 2014, 2101 patients were enrolled and 1945 were assigned to a treatment group according to their PET-2 result. In the PET-2-positive cohort, with a median follow-up of 73 months (IQR 59 to 94), 5-year progression-free survival was 89.9% (95% CI 85.7 to 94.1) in 217 patients assigned to eight cycles of eBEACOPP before the protocol amendment and 87.7% (83.1 to 92.4) in 217 patients assigned to eight cycles of rituximab plus eBEACOPP (p=0.40). Among 506 patients who received six cycles of eBEACOPP after the protocol amendment, 5-year progression-free survival was 90.1% (95% CI 87.2 to 92.9), with a median follow-up of 58 months (IQR 39 to 66). In the PET-2-negative cohort, with a median follow-up of 66 months (IQR 54 to 85) in the combined pre-amendment and post-amendment groups, 5-year progression-free survival was 91.2% (95% CI 88.4 to 93.9) in 446 patients who received eight or six cycles of eBEACOPP and 93.0% (90.6 to 95.4) in 474 patients who received four cycles of eBEACOPP (difference 1.9% [95% CI -1.8 to 5.5]). In the subgroup of PET-2-negative patients randomly assigned after protocol amendment, 5-year progression-free survival was 90.9% (95% CI 86.8 to 95.1) in 202 patients assigned to receive six cycles of eBEACOPP and 91.0% (86.6 to 95.5) in 200 patients assigned to receive four cycles of eBEACOPP (difference 0.1% [-5.9 to 6.2]). INTERPRETATION: Long-term follow-up confirms the efficacy and safety of PET-2-guided eBEACOPP in patients with advanced-stage Hodgkin lymphoma. The reduction from eight to four cycles of eBEACOPP represents a benchmark in the treatment of early-responding patients, who can now be potentially cured with a short and safe treatment approach.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Lancet: Haematology

ISSN

2352-3026

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

"e398"-"e409"

Kód UT WoS článku

000655263700009

EID výsledku v databázi Scopus

2-s2.0-85106533660