AW-03. Treatment strategy for the patients with relapsed and refractory classical Hodgkin lymphoma after PD-1 inhibitors failure: experience at the Pavlov University

Summary

The treatment strategy for relapsed and refractory classical Hodgkin lymphoma (r/r cHL) after PD-1 inhibitors failure is still not well-defined. Novel data demonstrating efficacy of PD-1 inhibitors with chemo- or targeted therapy of r/r cHL are accumulating. Nevertheless, the optimal combination, the sequence of the various therapy regimens and the place for allogeneic hematopoietic stem cell transplantation (allo-HSCT) are undefined. The aim of the study was to analyze the treatment strategy of patients with r/r cHL after nivolumab (N) failure.

Materials and methods

This retrospective study included 83 patients with r/r cHL who progressed or relapsed after PD-1 inhibitors monotherapy. All patients were treated with different combination of N and chemo- or targeted therapy. The median age was 33 (19-62). The primary chemoresistance was observed in 55 (66%) pts, early relapse in 8 (10%) pts. Previous autologous HSCT was performed in 28 (34%) pts, brentuximab vedotin (BV) in 39 (47%) pts. The median therapy lines before combination therapy was 5 (2-11). In this study, the best overall response (BOR) to first combination therapy (CT), PFS, OS and event-free survival (EFS) were analyzed. Event-free survival was defined as the time from the first CT to disease progression, relapse, death or initiation of other therapy. We also evaluated the treatment strategy of patients with r/r cHL after PD-1 inhibitors, including the place for allo-HSCT. The response was evaluated every 3 months by PET-CT using LYRIC criteria. Adverse events (AE) were analyzed by NCI CTCAE 4.0.3.

Results

The median follow up was 34 (7-55) months. Nivolumab combined with bendamustine, vinblastine, gemcitabine or BV as first CT was used in 35 (42%) pts, 27 (33%), 3 (4%), 18 (22%) pts respectively. The BOR to first CT was comp-lete response (CR) in 23 (28%) pts, partial response (PR) in 26 (31%), stable disease (SD) in 9 (11%), progressive disease (PD) in 9 (11%) and indeterminate response (IR) in 16 (19%) pts. Median PFS was 13 (95%CI: 10,9-15,0) months, 3-year PFS was 26.9%. Median OS was not reached, 3-year OS was 86.4%. Previous exposure to one of chemo- or targeted drugs used later in combination hadn’t significantly influenced PFS (p=0.995). Type of CT didn’t influence on PFS (p=0.48). Adverse effects (AE) occurred in 58 (70%) pts, including 3-4 grade AE in 13 (16%) pts. In 78 (94%) pts, additional therapy after the first CT was started. The median number of different CT types was 2 (1-4). Median EFS was 6 (95% CI:4.9-7.0) months. Allo-HSCT was performed in 21 (25%) pts after CT. The disease status before allo-HSCT was CR, PR, PD and IR in 3 (14%), 6 (29%), 8 (38%), 4 (19%) pts respectively. The median number of CT lines before allo-HSCT were 2 (1-3). There was a trend towards a better PFS in patients with one combination before allo-HSCT (p=0.073). At the same time, disease status before allo-HSCT didn’t influence PFS (p=0.509). Reasons for not proceeding to allo-HSCT were donor absence in 1 pts, patient refusal in 18 (22%) pts, disease progression in 15 (18%) pts, unsatisfactory somatic status or concomitant illnesses in 12 (14%) pts, several of the above reasons in 2 (2%) pts, unknown reasons in 10 (12%) pts. Two patients were at the stage of preparation for allo-HSCT during analysis.

Conclusion

The use of immunotherapy based strategy including N combinations and allo-HSCT after PD-1 inhibitors failure have potential to achieve long-term survival in patients with r/r cHL. The study underlines the importance of allo-HSCT timing. The determination of the optimal treatment structure in this patient group requires further prospective research.

Keywords

Hodgkin lymphoma, PD-1 inhibitors, immunotherapy, nivolumab.