Improving outcomes after allogeneic hematopoietic cell transplantation for Hodgkin lymphoma in the brentuximab vedotin era

Abstract

Allogeneic hematopoietic cell transplantation (allo HCT) remains a valuable alternative for relapsed/refractory (R/R) Hodgkin lymphoma (HL). Data on allo HCT outcomes in the era of new HL therapies are needed. We evaluated 72 R/R HL patients who received reduced intensity conditioning (RIC) allo HCT and compared the time periods 2009-2013 (n=20) to 2000-2008 (n=52). Grafts included HLA-matched sibling (35%), unrelated donor (8%) and umbilical cord blood (UCB, 56%). In recent period, patients more often received brentuximab vedotin (BV, 60% vs 2%), had fewer comorbidities (Sorror index 0: 60% vs 12%) and were in complete remission (50% vs 23%). Median follow-up was 4.4 years. Three-year progression-free survival (PFS) improved for patients treated between 2009-2013 (49%, 95% CI 26-68%) as compared to the earlier era (23%, 95% CI 13-35%, p=0.02). Overall survival (OS) at 3-years was 84% (95% CI 57-94%) vs 50% (95% CI 36-62%, p=0.01), reflecting lower non-relapse mortality and relapse rates. In multivariate analysis mortality was higher among those with chemoresistance (HR 3.83, 95% CI 1.38-10.57), while treatment during the recent era was associated with better OS (HR for period 2009-2013: 0.24, 95% CI 0.07-0.79) and PFS (HR 0.46, 95% CI 0.23-0.92). Allo HCT in patients with R/R HL is now a more effective treatment.

Brentuximab vedotin prior to allogeneic stem cell transplantation in Hodgkin lymphoma: a report from the EBMT Lymphoma Working Party

“…Unfortunately, patients with relapsed/refractory disease have already received multiple lines of therapy and are quite difficult to salvage. Preliminary data from small series suggest that pre‐transplant salvage therapy with BV might improve outcomes after allogeneic SCT for HL (Chen et al , , ; Hegerova et al , ).…”

“…Unfortunately, a significant number of patients with relapsed/refractory HL have chemo‐resistant disease and have received multiple lines of therapy. Therefore, novel monoclonal antibodies, such as brentuximab vedotin (BV), or checkpoint inhibitors are increasingly used as a bridge to transplant (Chen et al , , ; Ansell et al , ; Illidge et al , ; El Cheikh et al , ; Hegerova et al , ; Merryman et al , ).…”

“…Preliminary data suggests that BV may improve the results of allogeneic SCT for HL when used as a bridging agent (Chen et al, 2012a(Chen et al, , 2014Illidge et al, 2015;Hegerova et al, 2017). However, the impact on long-term outcomes remains unknown.…”

Brentuximab vedotin as salvage treatment in Hodgkin lymphoma naïve transplant patients or failing ASCT: the real life experience of Rete Ematologica Pugliese (REP)

“…Few data are available regarding BV before ASCT or allogeneic transplant (alloSCT), but preliminary results are encouraging [12,13,23]. Recently, updated data on survival after alloSCT from a single institution were presented, showing that the improved responses occurred in recent years and the reduced morbidity may be attributable to the use of BV as a safer and more effective salvage alternative before alloSCT [24]. Diversly, in a more recent report from the EBMT Lymphoma Working Party, patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT.…”

Haploidentical stem cell transplantation for patients with lymphoma: a position statement from the Lymphoma Working Party-European Society for Blood and Marrow Transplantation

“…Although chemo-(immuno)-therapy has a curative potential for a significant proportion of patients with HL or aggressive NHL, the percentage of chemo-refractory patients increases with each relapse and line of treatment. Allogeneic stem cell transplantation (alloSCT) is a valuable treatment option with curative potential for patients with relapsed or refractory NHL [1][2][3][4][5][6][7] and HL [8][9][10][11][12].…”