LY-03. Long-term multicenter study of nivolumab efficacy and safety in patients with relapsed and refractory classic Hodgkin lymphoma
Yaroslava V. Komarova1, Ludmila V. Fedorova1, Marina V. Demchenkova2, Maria V. Grigorieva2, Polina V. Kotselyabina1, Andrey M. Chekalov1, Elena E. Lepik1, Elena V. Kondakova1, Evgenia S. Borzenkova1, Vadim V. Baykov1, Marina O. Popova1, Ivan S. Moiseev1, Kirill V. Lepik1, Natalia B. Mikhailova1, Alexander D. Kulagin1
1 RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russia
2 Regional Oncological Clinic, Irkutsk, Russia
Contact: Dr. Yaroslava V. Komarova, phone: +7 (918) 043-17-31, e-mail: firstname.lastname@example.org
Nivolumab (Nivo) showed its efficacy in patients with relapsed and refractory classic Hodgkin lymphoma (r/r cHL) in clinical trials. Continued accumulation of the long-term experience in PD-1 inhibitors treatment is required to support previous data. Our aim was to evaluate long-term data on the efficacy and safety of Nivo therapy in patients with r/r cHL.
Materials and methods
A retrospective cohort of 182 patients was analyzed: 36% of patients (n=66) were treated with Nivo (40 mg); 64% (n=116) were treated with Nivo at a dose of 3 mg/kg in the RM Gorbacheva Research Institute and Regional Oncological Clinic in Irkutsk. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS) were analyzed. PFS was censored upon initiation of additional therapy. The response was evaluated every 3 mo by PET-CT using LYRIC criteria. Adverse events (AE) were analyzed by NCI CTCAE 5.0.
Patient characteristics included demographic parameters, data on previous therapy, chemoresistance, relapse rates, and disease stage at the time of Nivo initiation. Median follow-up was 54.9 mo (0.5-77.7). ORR was 68%, e.g., complete response (CR), 33%; partial response, 35%; stable disease, 7%; indeterminate response, 18%; progressive disease, 7% of cases. Median OS was not achieved, 5-year OS was 94.3% [95% CI: NA-NA]; median PFS was 19.2 mo [95% CI: 15.4-23.5]; 5-year PFS was 25.6% [95% CI: 17.5-34.6]. Several factors, including patients’ age, Nivo dose, number of previous therapy lines, prior auto-HSCT or brentuximab vedotin (BV) treatment have not had a statistically significant effect upon PFS. However, B-symptoms at Nivo initiation (median PFS, 35.6 mo [95% CI: 19.1-NA] vs 15.3 mo [95% CI: 11.5-19.3], p=0.0006); gender (median PFS in females was 23.4 [95% CI: 20.1-26.8] vs 13.7 in males [95% CI: 8.8-18.7], p=0.018), and early CR after 3 mo of Nivo therapy (median PFS 32 mo [95% CI: 20.4-NA] vs 17.9 mo [95% CI: 13.7-21.7], p=0.008) were significantly associated with PFS. Any grade of AE was detected in 72% of analyzed patients (n=173), including gr 3-4 AE in 21% of cases, and gr 5 AE in 2% of pts (2 secondary MDS, and one case of pneumonia). Additional therapy after Nivo was required in 78% of patients and included, e.g., Nivo monotherapy in 25%, chemotherapy (CT) in 7%, BV monotherapy in 7%, Nivo combined with CT or BV in 57%, allo- and auto-HSCT performed in 3% and 1% of patients respectively. Allo-HSCT was carried out in a total of 15% of patients after initial Nivo monotherapy, either immediately, or after additional therapy.
The obtained data demonstrate high efficacy and acceptable toxicity profile of Nivo therapy in the patients with r/r cHL. Such prognostic factors as absence of B symptoms at the time of Nivo initiation, female gender and early CR achievement were significantly associated with increased PFS duration. Since the Nivo therapy does not allow curation of the disease in most patients, some additional therapy after Nivo, including PD1 inhibitors, as well as allo-HSCT, may increase the survival rate in this group of patients.
Nivolumab, PD-1 inhibitors, immunotherapy, Hodgkin lymphoma, LYRIC criteria.