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Vol. 42. Issue S1.
Pages 11-12 (October 2020)
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Vol. 42. Issue S1.
Pages 11-12 (October 2020)
SP 21
Open Access
Relapsed and refractory classical Hodgkin lymphoma immunotherapy
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Kirill Lepik
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Liudmila Fedorova, Elena Kondakova, Yury Zalyalov, Andrey Kozlov, Marina Popova, Anastasia Beynarovich, Nikita Volkov, Polina Kotselyabina, Artem Gusak, Vadim Baykov, Alexandr Kulagin, Natalya Mikhailova

Background: Introduction of PD-1 inhibitor nivolumab (Nivo) into a clinical practice revolutionized the treatment of relapsed and refractory classical Hodgkin lymphoma (r/r cHL). Yet there is a set of unresolved clinical questions including the assessment of response, the prognostic factors influencing the survival of patients during immunotherapy, and optimal treatment strategy in patients resistant to nivolumab, as well as the possibility of discontinuation of therapy in case of persistent complete remission. This report presents the results of analysis of nivolumab treatment outcomes in Pavlov University.

Methods: This retrospective study included r/r cHL patients treated with standard-dose nivolumab (3mg/kg q2w). Therapy was continued until the disease progression, signs of intolerance or could be stopped at the discretion of treating physicians in selected patients with prolonged complete remission. In patients with r/r disease after nivolumab monotherapy, 48 received nivo and bendamustine (Benda) in a 28-day cycle. Benda (90mg/m2) was infused on day 1,2 and Nivo – on day 1 of the cycle. The response was assessed by PET-CT scan every 3 months according to LYRIC criteria.

Results: The analysis included 116 patients treated with nivolumab monotherapy (56m/60f) with a median age of 32 years (range 14–63). With a median follow-up of 41 (6–54) months after treatment initiation, 108 (93%) patients were alive, the median OS was not reached. Median PFS was 19mo (13.7–24.4) with a 3-year PFS of 27%. The best overall response was CR in 33%, PR in 34%, SD in 5%, PD in 9%, an indeterminate response (IR) in 20% of pts. Patients with early CR at 3mo after treatment initiation had significantly better prognosis (median PFS 35mo vs. 17mo, p=0.008). Other clinical factors that predicted prognosis were B-symptoms (median PFS 15mo vs. 26mo, p=0.017), extranodal disease at the moment of the treatment initiation (median PFS 14mo vs. NR, p=0.000), >4 prior lines of therapy (median PFS 18mo vs. 27mo, p=0.05). In a group of patients (n=23) who discontinued nivolumab in complete response (CR), the possibility of durable remission achievement was demonstrated (2-year PFS was 55.1%). The nivolumab retreatment has demonstrated the efficacy with high overall response rate (ORR) and CR (67 and 33.3% respectively). In the group of patients receiving nivo-benda combination after nivolumab monotherapy failure, the median follow-up was 29 (4–38) months, with the median PFS of 9.8mo (7.4–12.2). The median OS was not reached, 89.6% of patients were alive. The overall response rate (ORR) was 75% including complete remission (CR) in 44% pts. The progressive disease (PD) was the best response in 10% of pts. The allo-HSCT after Nivo was performed in 14 (29%) pts.

Conclusion: Nivolumab is highly efficient in the treatment of r/r cHL with early complete response, B-symptoms and extranodal disease at the treatment initiation being the most significant prognostic factor of PFS duration in our population of patients. The therapy may be discontinued in selected patients with complete remission. Combination of nivo with bendamustine is effective and safe approach for patients with r/r cHL after nivo monotherapy failure.

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Hematology, Transfusion and Cell Therapy
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