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

Background.

Hodgkin lymphoma (HL) is characterized by the presence of CD30-positive Hodgkin Reed-Sternberg cells. Approximately 30%–40% of patients with advanced disease are refractory to frontline therapy or will relapse after first-line treatment. The standard management of these patients is salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant (ASCT). The best prognostic factor is the status of disease before ASCT; in particular, the normalization of positron emission tomography (PET) scan. Brentuximab vedotin (BV) has shown a high overall response rate in refractory/relapsed HL after ASCT, whereas few data are available regarding its role before ASCT.

Patients and Methods.

A multicenter, retrospective, observational study was conducted. The primary endpoint of the study was the effectiveness of BV as single agent in patients with relapsed/refractory, ASCT-naïve HL, determined by the conversion of PET status from positive to negative; secondary endpoints were safety, capacity to proceed to ASCT, survival, and progression-free status.

Results.

Thirty patients with relapsed/refractory HL- and PET-positive disease after conventional chemotherapy salvage treatments were treated with a median of 4 cycles of BV. Normalization of PET findings (Deauville score ≤2) occurred in 9 of 30 patients (30%). Those nine patients proceeded to ASCT.

Conclusion.

These data suggest that BV can normalize PET status in a subset of HL patients refractory to conventional chemotherapy salvage treatments, such as ifosfamide-containing regimens, cytarabine- and platinum-containing regimens, prior to ASCT.

Implications for Practice:

Administration of brentuximab vedotin has resulted in a high overall response rate in refractory/relapsed Hodgkin lymphoma after autologous stem cell transplant, whereas few data are available regarding its role before transplant. The data suggest that brentuximab vedotin can normalize positron emission tomography results in a subset of patients refractory to conventional salvage treatments prior to transplant. Experience indicates that patients previously regarded as not ideal candidates for transplantation may be able to undergo further cytoreductive therapy using brentuximab vedotin.     

Autologous Bone Marrow Transplantation Followed by Involved Field Radiotherapy in Patients with Relapsed or Refractory Hodgkin's Disease

Twenty-six patients with refractory or relapsed Hodgkin's disease were treated with high dose cyclophosphamide, BCNU, etoposide, and thiotepa followed by autologous hematopoietic stem cell rescue. Involved field radiotherapy was given following hematologic recovery in selected patients. The overall response rate to the high dose chemotherapy was 69% with 34% complete responses. Following radiotherapy, the complete response rate increased to 50%. The predicted disease-free survival at two years is 22%. Toxicity with this regimen was significant, with five patients dying as a result of transplant related complications. We conclude that the addition of thiotepa to the standard CBV regimen did not result in improved therapeutic efficacy and possibly contributed significantly to the toxicity of the treatment.