Background: The aims of this study were to investigate the effect of brentuximab vedotin (BV) 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), and to identify prognostic factors in patients with a first relapse or primary refractory classical Hodgkin lymphoma (R/R cHL).
Methods: We collected individual patient data of 770 transplant eligible R/R cHL patients treated in prospective clinical trials, of whom n=386 were treated with BV and chemotherapy (BV-cohort), and n=384 with chemotherapy alone (Chemo-cohort), followed by ASCT [Fig1A]. The BV- and Chemo-cohorts were matched by propensity scores on baseline characteristics (i.e. relapsed/refractory, bulky disease, extranodal disease, stage I-II/III-IV, B symptoms and first-line treatment with BEACOPP). Matching was repeated 2000 times as internal validation and mean results are presented. Primary refractory disease was defined as no complete response on first-line treatment.
Results: After matching, there were no statistically significant differences in baseline characteristics between the cohorts [Fig1B]. The 3-year PFS was 73% (95%CI: 67-79%) in the BV-cohort compared to 67% (61-74%) in the Chemo-cohort (p=0.14) [Fig1C] and the 3-year OS was 93% (89-96%) versus 80% (75-86%) (p<0.001), respectively [Fig1D]. Primary refractory patients did not show any difference in PFS between the BV- and Chemo-cohorts (p=0.78), while patients with relapsed disease showed a significantly higher PFS in the BV-cohort (p=0.037) [Fig1E+F]. Logistic regression showed a significantly higher CMR rate for the BV-cohort compared to the CMR rate after BeGEV or ICE only (71.2% versus 63.1%; p=0.021), but there was no significant difference when compared to ICE-GVD (71.2% versus 76.4%; p=0.43). Cox regression for 3-year PFS showed high prognostic value for not achieving a CMR pre-ASCT (HR 2.0; p=0.002), stage III/IV (HR 2.0; p<0.001), B-symptoms (HR 1.8; p<0.001) and primary refractory disease (HR 1.7; p<0.001).
Conclusions: The addition of BV to salvage chemotherapy followed by ASCT seems to increase PFS in relapsed, but not in primary refractory cHL patients. This suggests that in patients who are chemotherapy resistant other treatment modalities, such as checkpoint inhibitors (CPI), should be considered.