Brentuximab Vedotin in Patients with R/R cHL in the Real World: What to Expect?

Introduction

For patients with R/R cHL, the standard of care includes administering high-dose chemotherapy followed by autologous HCT—if eligible for this approach. Approximately half of these cases involve a curative treatment approach. Patients at high risk of transplant failure include those with primary refractory disease, early relapse (within 12 months of starting treatment), or extranodal disease at relapse. The previous AETHERA study has indicated that using BV as maintenance therapy post-HCT can reduce such risks. The authors of this cited study focused on outcomes in high-risk cHL patients who underwent autologous HCT.  

Study Methods and Objectives

For the purposes of this retrospective real-world practice study, the records of all high-risk R/R cHL patients who underwent HCT at the authors' institution between 2010 and 2020 were evaluated for the effectiveness of brentuximab vedotin as maintenance therapy. The study cohort included 62 patients, 65% (n = 40) of whom were male.

All subjects were treated with the BEAM chemotherapy regimen (carmustine, etoposide, cytarabine, melphalan), followed by autologous HCT. Starting in 2014, BV was administered as maintenance therapy for up to 16 cycles. The analysis focused on overall survival (OS) and progression-free survival (PFS).

Results

In terms of the indications for maintenance therapy with brentuximab vedotin, it was most commonly administered due to early relapse (80%), followed by primary refractory disease (54%), and extranodal relapse (46%). Regarding risk factors, 37% of subjects had 1 risk factor present, 42% had 2, and 21% had 3. The most common salvage regimen used prior to HCT was ESHAP (56% of cases), followed by IGEV (32%). Approximately 45% of patients required more than one line of therapy, and 71% received BV as part of salvage therapy. In 55% of patients, PET/CT imaging performed before HCT documented a complete metabolic response (CMR), defined as a Deauville score ≤ 3. 

The median follow-up period after HCT was 19.3 months (range 1–89.2 months). The estimated proportion of patients reaching 2-year PFS and OS was 64.1% and 82.6%, respectively. Using BV as maintenance therapy resulted in significantly better outcomes compared to the non-BV group, both in terms of 2-year PFS (71.3% vs. 46.7%; p = 0.01) and 2-year OS (93.6% vs. 70.4%; p = 0.034). Multivariate analysis showed that significant factors affecting PFS were male gender (hazard ratio [HR] 6.8), refractory disease (HR 5.1), and maintenance therapy with brentuximab vedotin (HR 0.16). An interesting finding by the authors was that CMR status before HCT was significant in univariate analysis but not in multivariate analysis.

Brentuximab vedotin was administered as maintenance therapy in 3–16 cycles, with a median of 16 cycles. Adverse events recorded included grade ≥ 3 neutropenia requiring administration of granulocyte colony-stimulating factor (G-CSF) in 66% of patients, grade 1 peripheral neuropathy in 17%, and grade 2 in 3% of patients; neuropathy resolved or improved during follow-up. The dose was reduced due to adverse events in 26% of patients.

Conclusion

The authors concluded that consolidation with brentuximab vedotin resulted in better progression-free survival outcomes post-HCT in high-risk classical Hodgkin lymphoma patients. The significance of pre-HCT PET/CT under circumstances where BV is administered as maintenance therapy warrants further evaluation, according to the authors.

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Source: Damlaj M., Alahmari B., Alsadi H. et al. Contemporary outcomes of high risk relapsed refractory classical Hodgkin lymphoma patients − role of maintenance therapy in the real world. Poster. EBMT, 2022.