PS1239 NIVOLUMAB FOR TREATMENT OF PATIENTS WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN'S LYMPHOMA (CHL): CLINICAL AND PATIENT‐REPORTED OUTCOMES
Authors: Lepik K. , Mikhailova N. , Kondakova E. , Tsvetkova L. , Zalyalov Y. , Borzenkova E. , Moiseev I. , Baykov V. , Nikitina T. , Porfir’eva N. , Ionova T. , Afanasyev B. 
Published: June 2019

Background:

Treatment of pts with relapsed/refractory cHL is focused on achievement of survival benefits and improvement of patients’ quality of life (QoL).

Aims:

We aimed to evaluate clinical and patient‐reported outcomes of nivolumab (Nivo) as ≥3nd treatment line in pts with relapsed/refractory cHL.

Methods:

Pts with relapsed/refractory cHL who received Nivo 3 mg/kg q2w till disease progression, intolerance/toxicity of Nivo or refusal were included in the study. Treatment response was assessed using CT/PET‐CT in accordance with LYRIC criteria for response assessment of malignant lymphomas to immunotherapy. Safety was assessed in accordance with NCI CTCAE v. 4.03. For QoL assessment pts filled out RAND SF‐36 and EQ‐5D questionnaires, for symptom assessment – CSP‐Lym 41–1w questionnaire at baseline and at 3, 6, 9 and 12 mos after Nivo treatment start. Overall survival (OS) and progression‐free survival (PFS) were evaluated by the Kaplan‐Meyer method. For longitudinal QoL analysis paired t‐test, Wilcoxon test, Fridman ANOVA and χ2 test were used.

Results:

In total, 101 pts cHL (median age – 31 y.o., range 19–62, 52% males) who received 2–10 previous treatment lines were involved in the study. 90 out of 101 pts received Nivo as part of an named patient program. At the time of diagnosis 63.4% pts had advanced stage (III–IV), 61.4% ‐ primary chemotherapy resistance. Median follow‐up – 25 mos (3–31). Treatment response was registered in 64% pts: 32 (31.7%) pts achieved complete response, 33 (32.7%) – partial response. Stabilization and progression as the best response were registered in 5 (5.0%) and 10 (9.9%) pts, respectively. Indeterminate response was observed in 21 (20.8%) pts. The 2‐year OS was 96%; the median of OS was not achieved. The 2‐year PFS – 40.6%, the median of PFS was 17.9 mos. Adverse events were reported in 87.1% pts. Severe adverse events (III–IV grade) occurred in 18.8% pts. Analysis of QoL changes during treatment was performed in 87 pts. Before Nivo treatment start QoL was dramatically worsened for all SF‐36 scales. Significant QoL impairment was observed in 66% pts. All the pts experienced symptoms, 84% pts had moderate‐to‐severe symptoms. The most frequent (>80% pts) symptoms were quick tiredness, fatigue and decreased work energy. During Nivo treatment meaningful QoL improvement was revealed for all SF‐36 scales. Integral QoL Index significantly increased at 3, 6, 9 and 12 mos of treatment as compared to baseline: 0.298 at baseline vs 0.504 at 3 mos, 0.538 at 6 mos, 0.545 at 9 mos, 0.597 at 12 mos (p < 0.001). Proportion of pts with significant QoL impairment significantly decreased during treatment as compared to baseline: 66% before treatment, 32% at 3 mos, 34% at 6 mos (Cochran's Q test, p < 0.001). During treatment proportion of pts with no problems by EQ‐5D significantly increased by all 5 dimensions as compared to those pts with problems (Cochran's Q test, p < 0.01). EQ VAS significantly improved during treatment: 59.4 before treatment vs 80.6 at 12 mos (p = 0.006). The severity of the vast majority of symptoms (38/41) significantly decreased during 6 mos of treatment (p < 0.05). At 9 and 12 mos of treatment significant decrease of symptom severity was registered for more than 50% symptoms of CSP‐Lym 41–1w (p < 0.05).

Summary/Conclusion:

The results obtained in this observational study demonstrate high efficacy of Nivo as a monotherapy for relapsed/refractory cHL and its good tolerability. Nivo treatment leads to dramatic QoL improvement and significant decrease of symptom burden in this patient population.