Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma

Abstract

Key Points• BV and AVD followed by ISRT is well tolerated, without significant pulmonary toxicity. • BV and AVD followed by ISRT is an effective therapy for unfavorable-risk early stage HL, including bulky disease.This multicenter pilot study assessed the safety and efficacy of brentuximab vedotin (BV) and AVD (adriamycin, vinblastine, and dacarbazine) followed by 30 Gy involved site radiation therapy (ISRT). Patients with newly diagnosed, early stage classical Hodgkin lymphoma (HL) with unfavorable-risk features were treated with 4 cycles of BV and AVD.Patients who achieved a negative positron emission tomography (PET) scan (Deauville score of 1-3) received 30 Gy ISRT. Thirty patients received treatment and were assessable for toxicity. Twenty-nine patients completed 4 cycles of BV 1 AVD, and 25 patients BV 1 AVD 1 30 Gy ISRT. No clinically significant noninfectious pneumonitis was observed. Serious adverse events ( ‡grade 3) were reported in 4 patients, including febrile neutropenia, peripheral neuropathy, and hypertension. After 2 and 4 cycles of BV 1 AVD, 90% (26 of 29) and 93% (27 or 29) of patients achieved a negative PET scan, respectively. Two patients with biopsy-proven primary refractory HL were treated off-study. All 25 patients who completed BV 1 AVD 1 ISRT achieved a complete response. With a median follow-up of 18.8 months, by intent to treat, the 1-year progression-free survival is 93.3% (95% confidence interval, 84-102). Overall, the treatment was well-tolerated with no evidence of significant pulmonary toxicity. The majority of patients ( ‡90%) achieved negative interim PET scans after 2 and 4 cycles of BV 1 AVD. Excluding the 2 primary refractory patients, all patients are disease free, suggesting that this is a highly active treatment program even in patients with substantial disease bulk. This trial was

Use of flow cytometry in the phenotypic diagnosis of hodgkin's lymphoma

“…Interim PET was performed after two and four cycles and a metabolic remission after two and four cycles of treatment was observed in 90% and 93% of patients, respectively. At a median follow‐up of 18.8 months, the 1‐year PFS rate was 93.3% . Still, extended follow‐up is necessary for final conclusions.…”

Biology of classical Hodgkin lymphoma: implications for prognosis and novel therapies

“…[41][42][43] Recent efforts have been made to move BV into frontline treatment as a substitution for bleomycin in the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) schema. 44,45 The large international randomized ECHELON-1 trial set out to compare AVD-BV with ABVD and met the primary end point of a statistically significant improvement in modified progressionfree survival versus the control arm. 46 CD30 has also been explored as a target antigen for CAR T cells, which are patientderived CTLs that are ex vivo equipped with engineered receptor molecules consisting of a single-chain variable fragment fused to the signaling components of the T-cell receptor and costimulatory activation domains.…”

Brentuximab vedotin for the treatment of Hodgkin’s lymphoma

“…Specifically, investigators are assessing the safety and early efficacy of four cycles of BV + AVD chemotherapy followed by 30 Gray involved-site radiotherapy for the treatment for early stage, unfavorable risk HL [43]. The interim data presented at ASH 2014 of the first 19 of a planned 30 patients show 90% of the evaluable patients achieving negative interim PET scans after 2 cycles of BV and 4 cycles of AVD.…”