A phase 1 clinical trial investigating the combination of sonrotoclax plus zanubrutinib has demonstrated encouraging results in patients with relapsed/refractory mantle cell lymphoma (MCL), according to findings presented by Raul Cordoba, MD, PhD. The study revealed a favorable safety profile with notable absence of tumor lysis syndrome or atrial fibrillation, two complications commonly associated with MCL treatments.
Promising Efficacy Results
The combination therapy showed substantial antitumor activity, achieving a 78% overall response rate and a 70% complete response rate at the recommended dose of 320 mg. These response rates represent significant clinical activity in a patient population with limited treatment options, as relapsed/refractory MCL typically carries a poor prognosis.
The safety profile of the combination was particularly noteworthy, with researchers reporting no cases of tumor lysis syndrome, a potentially life-threatening complication that can occur when cancer cells are rapidly destroyed. Additionally, no atrial fibrillation was observed, which is significant given that cardiac complications can be a concern with certain lymphoma treatments.
Advances in MCL Treatment Landscape
The findings come amid broader advances in mantle cell lymphoma treatment approaches. The TRIANGLE study has established new standards for untreated MCL patients eligible for autologous stem cell transplantation (ASCT). This pivotal trial demonstrated that ibrutinib combined with R-CHOP and R-DHAP/R-DHAOx regimens improved both 4-year failure-free survival and overall survival compared to standard chemoimmunotherapy with ASCT.
Based on these results, ibrutinib plus chemoimmunotherapy, with or without ASCT, is now recommended for untreated MCL patients eligible for transplantation. The Committee for Medicinal Products for Human Use (CHMP) has recommended ibrutinib plus immunochemotherapy for previously untreated patients, reflecting the growing evidence base for targeted therapies in MCL management.
Clinical Implications
The sonrotoclax plus zanubrutinib combination represents a potential new treatment option for patients with relapsed/refractory disease, addressing a significant unmet medical need. The combination's favorable safety profile, particularly the absence of tumor lysis syndrome and atrial fibrillation, may offer advantages over existing therapies that carry these risks.
These developments highlight the evolving treatment paradigm in mantle cell lymphoma, where targeted therapies are increasingly being integrated into both frontline and relapsed/refractory settings. The promising response rates observed with sonrotoclax plus zanubrutinib warrant further investigation in larger patient cohorts to confirm these preliminary findings and establish the combination's role in MCL treatment algorithms.
