Brentuximab vedotin for relapsed or refractory CD30+ hematologic malignancies: the German Hodgkin Study Group experience

Abstract

The CD30-targeting Ab-drug conjugate brentuximab vedotin (SGN-35) was recently approved for the treatment of relapsed Hodgkin lymphoma and anaplastic large-cell lymphoma by the Food and Drug Administration. In the present study, we report the experience of the German Hodgkin Study Group with brentuximab vedotin as single agent in 45 patients with refractory or relapsed CD30 ؉ Hodgkin lymphoma who were treated either in a named patient program (n ‫؍‬ 34) or in the context of a safety study associated with the registration program of this drug. In these very heavily pretreated patients, an objective response rate of 60%, including 22% complete remissions, could be documented. The median duration of response was 8 months. This retrospective analysis supports the previously reported excellent therapeutic efficacy of brentuximab vedotin in heavily pretreated CD30 ؉ malignancies. This trial was registered at www.clinicaltrials.gov with identifier NCT01026233. (Blood. 2012;120(7): 1470-1472) IntroductionThe majority of Hodgkin lymphoma (HL) patients achieve longterm remission when treated with chemo-and radiotherapy. However, depending on initial risk factors and treatment, 10%-30% of patients progress or relapse. Up to 50% of these patients can still be cured with high-dose chemotherapy and autologous stem cell transplantation (ASCT). 1,2 Patients with primary progressive HL or relapse within 12 months after initial therapy have a significantly poorer outcome than those with late relapse. 3,4 Although salvage therapy including high-dose chemotherapy and ASCT cures up to 50% of patients, the median overall survival (OS) after ASCT failure is only approximately 2 years (Sally Arai, Michelle Fanale, Sven deVos, A.E., Tim Illidge, P.B., Anan Younes, Franck Morschhauser, Sandra J. Horning, manuscript submitted, June 2012). 5,6 To improve the outcome of patients with relapsed or refractory disease and to reduce chemotherapy-associated side effects, several targeted drugs have been developed and are currently undergoing clinical evaluation in HL patients. The most advanced and promising new drug is the Ab-drug conjugate brentuximab vedotin (SGN-35). 6 Brentuximab vedotin consists of the chimeric anti-CD30 mAb cAC10 conjugated to 4 molecules of monomethyl auristatin E, a synthetic antitubulin chemotherapeutic agent. 7 In a phase 1 trial including 45 patients with relapsed or refractory CD30 ϩ hematologic malignancies, an overall response rate (ORR) of 67% in patients who received the maximum tolerated dose of 1.8 mg/kg could be documented. 8 For relapsed HL, these promising results were confirmed in a single-arm phase 2 trial including 102 heavily pretreated HL patients. 9 The ORR was 73% with a median duration of 6.7 months, including 32% complete remissions (CRs) with a median duration of 20.5 months and 40% partial remissions (PRs) with a median duration of 3.5 months. In anaplastic large cell lymphoma, a phase 2 trial with 58 patients led to an ORR of 86% with a median duration of 12.6 months. 10 In August 2011, the Food ...

Advances in the treatment of Hodgkin lymphoma

“…These excellent data led to the approval of the drug in the US and in Europe. A report by the GHSG on patients with multiple relapses treated within a named patient program confirmed the excellent efficacy and tolerability of brentuximab vedotin [42]. Additional analyses on the use prior to aSCT, at relapse after aSCT and in transplant-naïve patients extend the promising findings on brentuximab vedotin [43][44][45].…”

Brentuximab Vedotin in Transplant-Naïve Relapsed/Refractory Hodgkin Lymphoma: Experience in 30 Patients

“…It has a rapid activity (three or four courses), including efficacy in inducing PET negativity in relapsed/refractory HL with a mild toxicity profile [20][21][22][23][24][25]. In this regard, limited data exist on the use of BV as a salvage therapy prior to ASCT [26][27][28].…”

High-dose melphalan with autologous stem cell support in refractory Hodgkin lymphoma patients as a bridge to second transplant

“…However, most of the patients progressed before receiving allo-SCT or auto-SCT (final ORR 29%). In the German study, 33 no patients underwent allo-SCT. Finally, in a study 34 addressing the question of BV as bridge to allo-SCT, 18 (out of 36 candidate) did not receive allograft, mainly because of patient preference (n = 18) or progressive disease (n = 7).…”