Novel Combination Regimen Brentuximab Vedotin-Bege Achieves Remarkable Efficacy in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma

Background

For patients with refractory or relapsed (R/R) classical Hodgkin lymphoma (cHL), large-scale clinical trials have demonstrated that a significant number of patients can achieve a cure with salvage chemotherapy followed by autologous stem cell transplantation (ASCT). Achieving complete remission (CR) through salvage chemotherapy is the most crucial prognostic factor for transplant-eligible patients and promotes long-term survival for non-transplant candidates. In a prospective trial of the BEGEV regimen (bendamustine, gemcitabine, vinorelbine) as second-line chemotherapy before ASCT in patients with R/R cHL, the CR rate was 73%. Of these, 43 underwent autografting, and 33 maintained CR at five years, indicating potential cures. To improve outcomes, we integrated brentuximab vedotin (BV) with the BEGEV regimen, excluding vinorelbine to reduce neuropathy, thereby creating the novel BV-BeGE (BBG) regimen. We retrospectively analyzed 11 R/R cHL patients at our center treated with the BBG protocol.

Methods

Eligible patients with R/R cHL after at least one systemic therapy were included in this study. Additional criteria required at least one measurable lesion and acceptable hepatic and hematologic function. Patients with secondary CNS involvement, transformed lymphoma or active infections were excluded. Eligible patients will receive four cycles of the BBG regimen (28 days per cycle). PET-CT scans were conducted every two cycles to evaluate efficacy according to the Lugano Classification 2014. For transplant-eligible patients, stem cells were harvested if remission was achieved after two cycles, and ASCT was performed after four cycles. For non-transplant candidates, treatment concluded after four cycles. BV maintenance was recommended post-ASCT for cHL patients with specific risk factors. The primary objective was to evaluate the CRR at the end of treatment (EOT).

Results

Between December 10, 2020, and May 20, 2024, a total of 11 patients were enrolled in the study. The median age was 37 ys (range 16-67ys), with male predominance (81.8%). At enrollment, ten patients (90.9%) were assessed as Ann Arbor stage III-IV. Five patients (45.4%) had extranodal involvement. All patients tested negative for EBV DNA at enrollment. Pathologically, CD30 positivity (in ≥5% of tumor cells) was detected in all specimens.

The median number of prior treatment lines was two (range 1-7), with five patients (45.4%) being primarily refractory. As of July 20, 2024, all 11 patients had completed at least two cycles of the BBG regimen, with an ORR of 90.9% and CRR of 81.8% after two cycles. One patient developed disease progression, while the remaining ten completed the prescribed four cycles of BBG, resulting in both ORR and CRR of 90.9% at EOT.

CD34+ cells were successfully harvested from all seven patients who were eligible for transplantation after two cycles of BBG. The median total yield of CD34+ cells was 6.7*10⁶ cells/kg (range 2.9-10.6). By the last follow-up, six patients had completed ASCT. Neutrophil and platelet engraftment was observed on a median of day 9.5 (range 9-10) and day 14.5 (range 10-27), respectively. One patient showed disease progression one month post-ASCT, while the others maintained CR. Three patients continued BV maintenance therapy post-ASCT, all maintaining CR.

The adverse events (AEs) during treatment were recorded as follows. Among hematologic toxicities, all patients experienced neutropenia, with grade 3-4 incidence of 45.5%, and 1 patient developed febrile neutropenia. The frequency of anemia and thrombocytopenia were both 45.5%. The most common non-hematologic toxicities were infections (36.4%), including 2 cases of COVID-19. Additionally, elevated transaminases, digestivetract hemorrhage and rash were also occasionally observed.

With a median follow-up duration of 13.8 months (95%CI 9.1-18.4), the median PFS and OS were not reached. 1-year PFS was 77.1%, and 1-year OS was 100%. In total, two patients experienced disease progression, and no patients had died at the last follow-up.

Conclusions

BV combined with BeGE (BBG) as salvage therapy in patients with R/R cHL has demonstrated satisfactory response rates and no unexpected AEs. For transplant-eligible patients, the BBG regimen can achieve a high CR rate of 90.9% and does not impair CD34+ stem cell mobilization after two cycles of treatment. Still, extended follow-up is needed to verify the long-term benefits.

No relevant conflicts of interest to declare.