Combination brentuximab vedotin and bendamustine for pediatric patients with relapsed/refractory Hodgkin lymphoma

Abstract

In patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL), achieving a complete metabolic response (CMR) following salvage therapy is associated with superior outcomes, and optimal treatments need to be identified. The combination of brentuximab vedotin and bendamustine (BVB), while highly active in adult patients, has not been extensively evaluated in pediatric patients with R/R HL. We performed a multi-institution retrospective review of pediatric patients <21 years of age with R/R HL treated with BVB from January 2016 to July 2019. Response was assessed by local radiologists according to Lugano classification criteria. Twenty-nine patients (17 relapsed, 12 refractory) with a median age of 15 years (range 10-20) were treated with BVB and received a median of three cycles of therapy (range 2-7). Patients received an infusion of 1.8mg/kg of brentuximab vedotin on day 1 with bendamustine 90mg/m2 on Days 1 and 2 of 3-week cycles. Nineteen patients (66%) achieved a CMR (CI: 46 to 82%). An objective response was observed in 23 patients (ORR 79%) (CI: 60 to 92%). The most common grade 3/4 toxicities were hematologic and 3 patients (10%) experienced grade 3 infusion reactions. Seventeen of 18 patients underwent successful mobilization and collection of stem cells. Sixteen patients (13 autologous, 3 allogeneic) received a consolidative transplant following BVB. The 3-year post-BVB event-free and overall survival was 65% (95%CI: 46 to 85%) and 89% (95%CI: 74 to 100), respectively. For pediatric patients with R/R HL, BVB was well tolerated and compares favorably with currently accepted salvage regimens.

Brentuximab vedotin in combination with bendamustine in pediatric patients or young adults with relapsed or refractory Hodgkin lymphoma

“…35,46,47 This drug combination has never been explored in prospective pediatric clinical trials, and only three retrospective series of children and young adults with R/R HL have been reported, namely, our cohort, an American multicentric cohort of 29 patients, and an English monocentric cohort of 29 patients. [37][38][39] In…”

“…The 3-year-EFS was 65%, while the OS was 89%. 38 McMillan et al administered the same doses employed in adults, postponing BV infusion (bendamustine was administered at a dose of 90 mg/m 2 on days 1 and 2, and BV at a dose of 1.8 mg/kg on day 2 of a 21-day cycle). 37 The median number of 21-day cycles administered was three (range: one to six).…”

“…28,50 With a median follow-up of 36 months (range: 8.7-86), in our cohort, the 3-year OS and PFS are 78.1% and 67%, respectively, these values being comparable to those reported in previous studies on R/R HL children. 28,31,37,38,48,51,52 Many studies have been published in the last years concerning the prognostic relevance of the interim PET/CT evaluation in the first-line setting (i.e., patients with poor prognosis at ERA evaluation). 53,54 In our study, ERA evaluation was performed in 28 patients, showing CR in 15 of them (54%) and PR in 13 (46%).…”

“…The treatment was well tolerated, and the toxicity profile was consistent with previously published data. 27,28,33,35,37,38 The most common treatment-related AE was grades 3-4 hematological toxicity in 14 patients (44%), which, however, did not cause treatment discontinuation in any patient. Peripheral neuropathy was observed in three patients (9%) and was reversible in all cases.…”

“…26,35,36 In the pediatric field, only two retrospective cohorts of 29 patients each have recently been reported, an American multicentric cohort and an English monocentric cohort, while prospective pediatric clinical trials have never explored this drug combination. 37,38 Similarly to adults, ORR in pediatric patients ranges from 79% to 83%.…”