ISSN 1866-8836
Клеточная терапия и трансплантация

Therapy of relapse and progression of classical Hodgkin lymphoma after allogeneic hematopoetic stem cell transplantation

Evgeniya S. Borzenkova, Natalia B. Mikhailova, Kirill V. Lepik, Lilia V. Stelmakh, Anastasia V. Nekrasova, Ivan V. Tsygankov, Ivan S. Moiseev, Yuri R. Zalyalov, Elena I. Darskaya, Sergey N. Bondarenko, Boris V. Afanasyev
R. M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation; First St. Petersburg I. Pavlov State Medical University, St. Petersburg, Russia

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Cellular Therapy and Transplantation (CTT)
Volume 7, Number 3
Contents 

Summary

Introduction

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.

Results

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).

Conclusion

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.

Keywords

Hodgkin lymphoma, allogeneic hematopoetic stem cell transplantation, brentuximab vedotin, nivolumab.
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