A subset analysis of the randomised, double-blind, placebo-controlled phase III CHRONOS-3 study that focused on patients with relapsed marginal zone lymphoma, showed superior efficacy of treatment with a PI3K inhibitor, copanlisib plus rituximab compared to placebo plus rituximab. The safety profile of copanlisib plus rituximab was consistent with copanlisib and rituximab given as monotherapy. The results were reported by Prof. Muhit Özcan of the Department of Haematology, Ankara University School of Medicine in Ankara, Turkey during the proffered papers session on haematological malignancies at ESMO Congress 2021 (16-21 September).
Prof. Özcan told the audience that the CHRONOS-3 study showed a 48% risk reduction in disease progression/death with combination treatment of copanlisib plus rituximab compared to placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma. In this study, patients with relapsed indolent non-Hodgkin lymphoma who were progression- and treatment-free for at least 12 months after rituximab-based therapy or at least 6 months if unwilling/unfit to receive chemotherapy were randomised 2:1 to copanlisib plus rituximab or placebo plus rituximab. The study primary endpoint was centrally assessed progression-free survival (PFS).
Among 458 patients enrolled in the CHRONOS-3 study, 66 with marginal zone lymphoma were randomised to copanlisib plus rituximab and 29 to placebo plus rituximab. Subtypes of marginal zone lymphoma included in the analysis were nodal (39%), extranodal (37%), and splenic (24%). With a median follow-up of 18.0 months, treatment with copanlisib plus rituximab significantly reduced the risk of disease progression/death compared to placebo plus rituximab.
In the overall population with marginal zone lymphoma, median PFS was 22.1 month with copanlisib plus rituximab versus 11.5 month with placebo plus rituximab (hazard ratio 0.475; 95% confidence interval 0.245,0.923; p= 0.012). Similar results to overall marginal zone lymphoma population were seen in the subgroups of patients with nodal and extranodal disease.
The objective response rate improved with copanlisib plus rituximab; it was 75.8% in the overall marginal zone lymphoma population versus 41.4% in those treated with placebo plus rituximab.
Median duration of response was 25.4 month for copanlisib plus rituximab versus 9.3 month for placebo plus rituximab; median time to progression was 33.2 month versus 11.5 month. Median overall survival was not evaluable.
Most common treatment-emergent adverse events (TEAEs; all grade/grade 3+) with copanlisib plus rituximab were hyperglycaemia (65%/54%) and hypertension (54%/45%). Most common TEAEs with placebo plus rituximab were hyperglycaemia (24%/10%), cough (24%/0%) and upper respiratory tract infection (24%/0%). Serious TEAEs were higher with copanlisib plus rituximab (57%) versus placebo plus rituximab (28%). TEAEs deemed related to copanlisib/placebo included hyperglycaemia (63%/24%) and hypertension (54%/17%).
The authors concluded that copanlisib is the first PI3K inhibitor to be safely combined with rituximab in a phase III setting in patients with relapsed marginal zone lymphoma and represents a potential new therapeutic strategy in these patients.
The study was funded by Bayer AG.
826O – Özcan M, Jin J, Szomor A, et al. Copanlisib plus rituximab vs placebo plus rituximab in patients (pts) with relapsed marginal zone lymphoma (MZL) treated in the phase III CHRONOS-3 trial. ESMO Congress 2021 (16-21 September).