Matthew J. Matasar, MD, on the Clinical Implications of the Phase 3 CHRONOS-3 Study

The lymphoma expert discussed how adding copanlisib to rituximab improved progression-free survival, while demonstrating a manageable safety profile in patients with relapsed indolent non-Hodgkin lymphoma.

Adding copanlisib (Aliqopa) to rituximab (Rituxan) reduced the risk of disease progression or death, compared with rituximab plus placebo, in patients with relapsed indolent non-Hodgkin lymphoma, according to primary results from the phase 3 CHRONOS-3 study (NCT02367040).

At the virtual American Association for Cancer Research Annual Meeting, Matthew J. Matasar, MD, presented results from the trial, showing that the median progression-free survival with copanlisib/rituximab was 21.5 months (95% CI, 17.8-33.0) compared with 13.8 months (95% CI, 10.2-17.5) with rituximab/placebo (HR, 0.520; 95% CI, 0.393-0.688; P <.0001). Moreover, the combination demonstrated a manageable safety profile that was consistent with prior reports of copanlisib and rituximab as single agents.

“Our hope is that with copanlisib…[we] might be able to overcome those challenges and prove to be a safe and effective medicine when combined with rituxumab.,” Matasar, associate member of Lymphoma Service, Department of Medicine, at Memorial Sloan Kettering Cancer Center, said in an interview with CancerNetwork®.

He further discussed the trial results and the clinical implications they may have for patients with relapsed indolent non-Hodgkin lymphoma.


The takeaway here is that the combination of copanlisib with rituximab was shown to be safe and effective. Safe, meaning we didn’t find any unexpected toxicities or signal that wasn’t expected given what we know about the agents alone, and effective, meaning that it significantly improved progression-free survival. Patients on average were able to stay in remission longer with the combination than with rituximab alone.

I think that these data really do support the use of the combination of rituximab with copanlisib as a standard treatment for patients with indolent relapsed B-cell lymphomas whose disease has been sensitive to rituximab in the past. I really think that this establishes the treatment as safe and effective and a very reasonable consideration for such patients.

We’re continuing to work on how best to leverage copanlisib in clinical practice. We’ve recently completed a sister study called CHRONOS-4, which is again a randomized clinical trial comparing rituximab in combination with bendamustine or rituximab plus CHOP [cyclophosphamide, doxorubicin, vincristine and prednisone], with or without copanlisib, to see whether copanlisib can be safely combined with chemoimmunotherapy to improve outcomes for patients with indolent lymphomas.


Matasar MJ, Capra M, Ozcan M, et al. CHRONOS-3: randomized phase III study of copanlisib plus rituximab vs rituximab/placebo in relapsed indolent non-Hodgkin lymphoma (iNHL). Presented at: 2021 AACR Annual Meeting 2021; April 10-15, 2021; virtual. Abstract CT001.