Frontline brentuximab vedotin as monotherapy or in combination for older Hodgkin lymphoma patients.

Abstract

8032 Background: Older patients with classical Hodgkin lymphoma (cHL) have poor outcomes relative to younger patients, often due to comorbidities and toxicities related to standard first-line (1L) chemotherapy (5-yr PFS: 30%–45% vs 75%–80%) (Evens 2008; Proctor 2009). Brentuximab vedotin (BV, ADCETRIS®), a CD30-directed antibody-drug conjugate, has robust activity in patients refractory to several lines of chemotherapy. Methods: This phase 2, open-label study, SGN35-015 (NCT01716806), evaluated efficacy and tolerability of BV alone or combined with single-agents in treatment-naive cHL patients ≥60 yr. The full-analysis set (FAS) includes all patients who received BV (1.8 mg/kg IV). Patients in Part A received BV monotherapy on Day 1 of every 3-week cycle (n = 26); Part B: BV+dacarbazine (DTIC; 375 mg/m2; n = 19); Part C: BV+bendamustine (benda; 70 mg/m2; n = 20); and Part D: BV+nivolumab (nivo; 3 mg/kg; n = 20). The efficacy evaluable (EE) set includes all patients who had at least 1 post-baseline response assessment (n = 25, 19, 17, 19). Results: Demographic characteristics were generally similar: median age 78, 69, 75, and 72 yr in Parts A, B, C, and D, respectively, and 62% of patients (range 45%–70%) reported impaired physical functioning at baseline. Most patients had disease stage III/IV (62%, 68%, 75%, 80%), were ECOG 0/1 (77%, 74%, 80%, 95%), and male (54%, 68%, 50%, 75%). Median time from diagnosis was 1.2 to 1.5 mo (FAS; 10 Jan 2019 data cutoff). ORR were high (92%, 100%, 100%, 95%) at a median follow-up of 59.4, 58.6, 51.3, and 19.4 mo in the EE data set. Median OS in the FAS set was 77.5 mo with monotherapy; 64.0, 46.9, and not reached in the combination parts. Treatment-related AE ≥ Grade 3 occurred in 50%, 37%, 70%, and 60% of patients; peripheral neuropathy (PN) was most common (35%, 26%, 20%, 35%). Treatment-related SAEs occurred in 12%, 11%, 40%, and 5% of patients. Part C enrollment (BV+benda) closed early due to multiple acute toxicities. There were no treatment-related deaths in any part of the study. The median treatment cycles per patient were 8.0, 12.0, 5.0, and 14.5. Treatment discontinuation due to related AEs occurred in 42%, 42%, 40%, and 30% of patients, most commonly due to PN (38%, 37%, 30%, 20%). Conclusions: Older patients with cHL and multiple comorbidities have very high response rates with BV as monotherapy or combined with other single agents and improved tolerability versus combination chemotherapy. Median overall survival exceeded 6 yr with BV monotherapy. BV+nivo or BV+DTIC appeared to be the most reasonable combination treatment options in this study. Clinical trial information: NCT01716806 .

Durable Remission in Hodgkin Lymphoma Treated With One Cycle of Bleomycin, Vinblastine, Dacarbazine and Two Doses of Nivolumab and Brentuximab Vedotin

“…BV is an antibody drug conjugate targeting CD 30 that has shown promising single-agent activity in relapsed/refractory HL [ 11 , 12 ]. Also, frontline BV monotherapy in elderly patients has yielded outstanding results with an ORR of 92% and median OS of 77.5 months [ 13 ]. Friedberg et al reported a phase 2 nonrandomized study of BV plus dacarbazine in newly diagnosed classical HL patients older than 60 years (n = 22) ineligible for cytotoxic chemotherapy.…”

Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies

“…Another trial assessed the BV-Nivo combination in 21 patients. After a median follow-up of 26.2 months, the ORR was 95% and the median PFS was not reached [30]. For more fragile, unfit, elderly patients, BV alone or in combination with dacarbazine may also represent well-tolerated and beneficial approaches [30,31].…”

Hodgkin lymphoma. ASCO, EHA and ASH 2020 news

“…Первые сообщения об успешном применении брентуксимаба ведотина в 1-й линии терапии в монорежиме или в сочетании с химиопрепаратами и иммунотерапией у пациентов с кЛХ старшей возрастной группы сделаны более 5 лет тому назад. В декабре 2020 г. на 62-й конференции ASH C. Yasenchak привел результаты анализа выживаемости больных старше 60 лет, получавших BV в монорежиме или в сочетании с дакарбазином, или бендамустином, или ниволумабом [5]. На рис.…”

“…Режимы применения брентуксимаба ведотина в монорежиме и в комбинации с химиопрепаратами и иммунотерапией у пациентов с кЛХ в старшей возрастной группе (адаптировано[5]). The regimen of brentuximab vedotin application as alone or in combination with chemotherapy and immunotherapy in patients with cHL of an elderly section (adapted from[5]). …”

“…. ОВ (а) и ВБП (б) пациентов с кЛХ старшей возрастной группы, получивших в 1-й линии терапии BV в монорежиме или в сочетании с дакарбазином, бендамустином или ниволумабом (адаптировано[5]). Fig.6.…”