Therapy of relapse and progression of classical Hodgkin lymphoma after allogeneic hematopoetic stem cell transplantation
Allogeneic hematopoetic stem cell transplantation (allo-HSCT) has the curative potential for patients with relapsed and/or refractory classical Hodgkin lymphoma (cHL). Nevertheless, published data about therapy of relapse or progression (r/r) of cHL after alloHSCT is limited. The aim of single-center retrospective study was to identify prognostic factors in treatment of r/r cHL patients after allo-HSCT.
Patients and methods
This retrospective analysis included patients with r/r cHL (n=27), who had undergone allo-HSCT in our center from 2002 to 2017. Patients with documented relapse or progression of cHL after allo-HSCT were represented by 22.2% (n=6); patients with documented CR after allo-HSCT, but had relapse further, were represented by 25.9% (n=7); patients with first disease status after alloHST worse than CR (PR/SD) comprised 51.8% (n=14), including 7 patients with non-documented 1st disease status, such as PR/SD, based on cHL status before allo-HSCT, herewith CR and PD also were no documented. At the first staging after alloHSCT, CR was achieved in 7 patients (25.0%), PR was achieved in 10 patients (37.0%), 17 (62.9%) patients had objective response. Further on, 20 patients (74.0%) of 27 had progression or disease relapse after allo-HSCT, 19 patients of them received treatment, i.e., six patients of 20 received only chemotherapy (c/t; chemo) after allo-HSCT (ChVPP, LABO, vinblastine); 13 patients of 20 received novel monoclonal antibodies (Mabs), including brentuximab vedotin (BV) and nivolumab (Nivo), or their combination with chemotherapy. 8 patients of 20 did not receive treatment of cHL: three patients, due to other complications and poor performance status, and 5 patients with no documented 1st disease status (PR-1, SD-1) were at dynamic observation. BV-based regimens were used as the first-line Mab-therapy in all 13 Mab-treated patients (48.1%). Seven of them (53.8%; 25.9%), due to continuous progression, were transferred to second Mab- therapy line (with Nivolumab). Before treatment by Mab (BV) 5 of 13 patients received chemotherapy and 4 patients from 13 had got donor lymphocyte infusion (DLI). The patients characteristics are presented in Table 1.
At the time of analysis, the median follow-up period was 27 (1.4-3.7) months. For patients with chemotherapy only, (n=6) median follow-up was 25 (6.27-55) months, patients with Mab-therapy (including combination with chemo) (n=13), 45mo (range, 23-73), and for non-treated patients (n=8), the median follow-up was 11 months (1.47-39.37). The median interval to progression/relapse of disease was 3.6 mo (1.3-11.3mo). Overall survival (OS) at the moment of analysis was 55% (15/27). The median interval between alloSCT and first dose of BV due to PD/RD was 4.7 (1.7- 44) mo. The median interval between alloSCT and first dose of Nivo was 38.7 months (range, 14.5-44.5). The median interval between last dose of BV and first dose of Nivo was 2.83 (1.23-32.47) months. At the moment of analysis 12 patients (44.4%) died: six with Hodgkin lymphoma progression, and six other patients were lost due to severe chronic GVHD (chGVHD) and infectious complications over post-transplant period, including 3 patients with Mab therapy, and one patient from the group of dynamic observation. 15 patient are alive: four patients with dynamic observation had achieved CR; six patients had achieved CR after Mab-therapy (5) and chemotherapy (1); 5 patients are continuing treatment because of stable or progressing disease. When compared with chemotherapy, Mab-therapy had prognostic significance (76.9% vs 16.7%, p=.003). Development of chGVHD also had prognostic significance (72.7% vs 43.9%, p=.084).
As based on a limited clinical material, we have demonstrated that the lymphoma progression was the cause of lethal outcomes in one third of patients, and therapy-related complications were fatal in almost the same number of patients. Despite relatively favorable outcome in heavily pretreated patients, further studies are required to determine optimal therapy for post-transplant relapse of cHL.
Hodgkin lymphoma, allogeneic hematopoetic stem cell transplantation, brentuximab vedotin, nivolumab.