Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged ≥60 years with HL

Abstract

Patients aged ≥60 years with treatment-naive Hodgkin lymphoma (HL) have few treatment options and inferior survival due to treatment-related toxicities and comorbidities. This phase 2, nonrandomized, open-label study evaluated brentuximab vedotin (BV) monotherapy (results previously reported), BV plus dacarbazine (DTIC), and BV plus bendamustine. Patients had classical HL and were ineligible for or declined frontline chemotherapy. Twenty-two patients received 1.8 mg/kg BV and 375 mg/m DTIC for up to 12 cycles, and 20 more patients received 1.8 mg/kg BV plus 90 or 70 mg/m bendamustine for up to 6 cycles (dose reduced due to toxicity). Subsequent BV monotherapy was allowed. Approximately 30 patients were to receive BV plus bendamustine; however, the incidence of serious adverse events (65%) and 2 deaths on study led to discontinuation of bendamustine and cessation of enrollment. Most patients had stage III/IV disease, and approximately half had ≥3 comorbidities or were impaired in ≥1 aspect that significantly interfered with quality of life. For BV plus DTIC, the objective response rate (ORR) was 100% and the complete remission (CR) rate was 62%. To date, the median progression-free survival (PFS) is 17.9 months. For BV plus bendamustine, the ORR was 100% and the CR rate was 88%. Neither the median PFS nor overall survival was reached. For elderly patients with HL, BV plus DTIC may be a frontline option based on tolerability and response duration. Despite activity, BV plus bendamustine is not a tolerable regimen in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01716806.

Hodgkin lymphoma in the elderly: new perspectives and a 10‐year monocenter real‐life experience

“…We confirm in our real‐life experience elderly HL patients are characterized by less favourable outcome if compared to published data about younger patients. Our study has some limitations, above all it is a retrospective analysis of a small sample size, even if comparable to previously published experiences . We recommend baseline CGA and suggest ABVD could represent a useful option with curative intent for a group of fit patients ≤70 years old .…”

“…BV was associated with bendamustine or dacarbazine in 42 older HL patients ineligible for ABVD; bendamustine arm was interrupted because of toxicity. BV plus dacarbazine arm achieved a CR rate of 62% with a median PFS of 17.9 months . In a recent trial, BV was associated with cyclophosphamide, doxorubicin and prednisone (B‐CAP); 1‐year PFS was 73.9%, grade 4 leukopenia and grade 3 peripheral neuropathy were observed in 41% and 20% of cases, respectively .…”

The treatment of older Hodgkin lymphoma patients

“…A total of 65% of the patients experienced adverse events and two of the patients (10%) died due to treatment‐induced toxicity, resulting in discontinuation of the brentuximab vedotin plus bendamustin arm of the study. The combination of brentuximab vedotin with dacarbazine was better tolerated, however the CR rate was only 62% and the median PFS was 17·9 months (Friedberg et al , ).…”

Doxorubicin, vinblastine, dacarbazine and lenalidomide for older Hodgkin lymphoma patients: final results of a German Hodgkin Study Group (GHSG) phase‐I trial

“…In accordance with previous results using ABVD, this suggests that AVD might not be the ideal chemotherapy‐backbone for simultaneous combination to novel substances in older HL patients (Böll et al , ; Evens et al , ). The combination of BV with bendamustine or dacarbazine in older HL patients resulted in premature termination of the bendamustine combination due to unexpected toxicity and no indication of superior efficacy with BV plus dacarbazine (Friedberg et al , ). Evens et al () recently reported the results of a multicentre phase II study of BV sequentially before and after six cycles AVD for older advanced stage HL patients, including 48 patients with a median age of 69 years and a median CIRS‐G score of 7.…”