ASH 2021 | Brentuximab vedotin plus chemotherapy prior to ASCT in R/R Hodgkin lymphoma
Julia Driessen, MBBS, University of Amsterdam, Amsterdam, The Netherlands, shares the findings from a study aiming to investigate the effect of brentuximab vedotin addition to salvage chemotherapy compared to chemotherapy alone on progression-free survival (PFS), overall survival (OS), and complete metabolic response (CMR) rate prior to autologous stem-cell transplant (ASCT) in patients with a first relapse or primary refractory (R/R) classical Hodgkin lymphoma. Results demonstrated that the addition of brentuximab vedotin to salvage chemotherapy followed by ASCT increased PFS in relapsed but not in primary refractory patients. This finding suggests that other treatment strategies such as checkpoint inhibitors should be considered in chemotherapy-resistant patients. An increase in OS for the brentuximab vedotin cohort was also observed. Additionally, the study confirmed the prognostic value of pre-ASCT CMR for PFS and b-symptoms, stage, and primary refractory disease as prognostic factors for PFS and pre-ASCT CMR. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
For patients with relapsed and refractory Hodgkin lymphoma, the standard treatment is currently chemotherapy followed by autologous stem cell transplant. Patients have a long-term progression-free survival of about 60% to 70% so there is certainly room for improvement in this. A few new novel drugs have come on the market in the past decades of which one is brentuximab vedotin, which is a CD30 antibody drug conjugate...
For patients with relapsed and refractory Hodgkin lymphoma, the standard treatment is currently chemotherapy followed by autologous stem cell transplant. Patients have a long-term progression-free survival of about 60% to 70% so there is certainly room for improvement in this. A few new novel drugs have come on the market in the past decades of which one is brentuximab vedotin, which is a CD30 antibody drug conjugate.
The other is immunotherapy with PD-L1 inhibitors. Now, several Phase II clinical trials have been done that investigated the additional of brentuximab vedotin into chemotherapy prior to autologous stem cell transplant, but there are no randomized controlled trials that compare BV and chemo to chemotherapy alone. There are also no Phase III trials that are currently running or that are being set up. That’s why we started to collect individual patient data from all the Phase II studies that have been performed to compare the addition of BV to chemotherapy to chemotherapy alone.
We contacted all the authors and collected all the data and then we performed a matched analysis on all the BV studies versus chemo studies. So we performed an individual patient’s matched analysis on BV addition to chemotherapy. We matched the BV studies to the chemo cohorts. We matched by several baseline characteristics such as Stage B symptoms, primary refractory status, external disease and bulky disease.
These variables were equally distributed among the cohorts. And then, we compared the progression-free and overall survival over time. So the three-year progression-free survival is improved in patients that had relapsed disease at baseline, but not in primary refractory patients. For relapsed patients, it seems that the addition of BV to chemotherapy increases progression-free survival, but for refractory patients, not.
So we hypothesized that, refractory patients who are refractory to chemotherapy are also more likely to not respond to extra production of vedotin. Furthermore, we also compared the complete metabolic response rate prior to autologous stem cell transplant in which you also see an increase primarily in relapsed patients. In refractory patients, there was a small increase but not a significant increase.
Then for the overall survival, we also observed an increase in the BV cohort, but this could also be due to advances in treatments over time for patients who fail ACT because, novel drugs such as checkpoint inhibitors were not yet available at the time of the chemo studies. So, there could be a bias of that in the study.
I think, the most important points are that, the BV addition to chemotherapy can increase the progression-free survival in relapsed patients but not in primary refractory patients, and that the overall survival increased over time. Besides, we also investigated the prognostic value of several baseline characteristics. We found that, primary refractory status is very important, but also B symptoms.
Patients with B symptoms have a much lower survival rate compared to patients without B symptoms. So, in future trials, there could be more attention, I think, for patients with B symptoms and patients with primary refractory disease to improve the results, particularly in that group of patients.
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