Consolidation with ADCT-402 (loncastuximab tesirine) after a short course of immunochemotherapy: a phase II study in BTKi-treated (or BTKi intolerant) Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) patients

The treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL) remains a highly debated topic, particularly in patients who have already received Bruton tyrosine kinase inhibitors (BTKi). While these agents were originally reserved for R/R patients, their use is now progressively being moved earlier in the treatment sequence. This shift will make the management of such patients increasingly complex, with fewer therapeutic options available. 
Additionally, a subset of patients may experience intolerance to these agents, further highlighting the need for alternative treatments that are both safe and effective. 
One treatment regimen that has demonstrated good efficacy and safety in R/R MCL patients post-BTKi therapy is the chemoimmunotherapy combination R-BAC (rituximab, bendamustine, cytarabine). However, R-BAC alone is not capable of producing durable responses. 
Recently, a novel antibody-drug conjugate, loncastuximab tesirine (ADCT-402), has shown very promising results in R/R MCL. Nonetheless, its use as monotherapy is unlikely to provide long-term disease control in such complex cases. 
Therefore, we have designed a phase II study that proposes an initial salvage treatment with the R-BAC regimen, followed by consolidation with loncastuximab tesirine administered for a limited number of infusions to minimize the risk of long-term toxicity. 
This study aims to generate preliminary data on efficacy and toxicity, forming the foundation for future clinical investigations.