AW-03. Treatment strategy for the patients with relapsed and refractory classical Hodgkin lymphoma after PD-1 inhibitors failure: experience at the Pavlov University
Liudmila V. Fedorova, Kirill V. Lepik, Elena V. Kondakova, Evgenia S. Borzenkova, Anastasia V. Beynarovich, Polina V. Kotselyabina, Marina O. Popova, Ivan S. Moiseev, Natalia B. Mikhailova, Alexander D. Kulagin
RM Gorbacheva Research Insitute, Pavlov University, St.Petersburg, Russia
Dr. Liudmila V. Fedorova, phone: +7 (921) 770-49-92, e-mail: firstname.lastname@example.org
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.
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.
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.
Hodgkin lymphoma, PD-1 inhibitors, immunotherapy, nivolumab.