Efficacy and Safety of Obinutuzumab Preemptive Treatment at the Time of the Molecular Relapse

Patients with evidence of MCL molecular relapse defined as an increasing copy number in quantitative real-time polymerase chain reaction (RQ-PCR) of clone-specific immunoglobulin heavy chain (IGH) gene rearrangements or BCL1-IGH fusion genes according to BIOMED-2 methodology and protocols in peripheral blood or/and bone marrow without evidence of clinical relapse/progression after auto-HCT procedure with all inclusion and no exclusion clinical trial criteria will receive 4 weekly infusions of obinutuzumab (1000 mg, iv) on day 1, 8, 15, 22.Response assessment in bone marrow and/or peripheral blood and CT/MRI imaging will be performed 2 months after the obinutuzumab preemptive treatment. Patients with subsequent molecular remission in peripheral blood and/or bone marrow confirmed in RQ-PCR (with 10-4 level of sensitivity) assessment and no signs of relapse/progression according to the Lugano Classification will be further followed. From this moment, evaluation of response will be performed every 6 months with computed tomography/magnetic resonance (CT/MR) imaging and bone marrow aspiration to detect classical relapse/progression and/or to detect subsequent molecular relapse by quantitative real-time polymerase chain reaction (RQ-PCR) of clone-specific immunoglobulin heavy chain (IGH) gene rearrangements or BCL1-IGH fusion genes with the use of consensus JH probes and specific ASO primers. Patients will be monitored every 3 months (outpatient visits with peripheral blood samples for MRD assessment to detect molecular relapse by quantitative RQ-PCR of clone-specific immunoglobulin heavy chain (IGH) gene rearrangements or BCL1-IGH fusion genes). Preemptive treatment can be administered in subsequent molecular relapses/progressions.