He began by reviewing how MCL patients were treated historically with R-CHOP or rituximab + bendamustine (R-Benda) in both, front-line and the relapsed/refractory (R/R) settings. Young and fit patients received autologous stem cell transplantation (ASCT) before undergoing allogeneic stem cell transplantation (allo-SCT) at first relapse. He highlighted the need to rethink treatment for MCL with the advent of ibrutinib, which is particularly efficacious in patients who have received only one prior therapy.
Durable responses lasting more than 2 years can be achieved in 50% of patients with ibrutinib as a monotherapy. Despite advocating for ibrutinib to be used as a second-line treatment in all patients, he pointed out that in the high-risk group of younger, fit patients with a p53 mutation, ibrutinib should merely be used as a bridging therapy before allo-SCT due to their high risk of relapse. As part of combination therapy (for example, RLI), high ORR and complete response (CR) have been demonstrated in patients with relapsed MCL (regardless of p53 type). Furthermore, the AIM trial showed similar benefits of ibrutinib in combination with venetoclax for newly diagnosed MCL patients.
Prof. Rule went on to discuss novel therapies being used for front-line treatment of MCL. He mentioned the Lyma-101 trial (the results of which were presented at the 24th European Hematology Association Congress, summarised on lymphoma hub here), which assessed obinutuzumab and dexamethasone, high dose cytarabine and cisplatin (O-DHAP) followed by consolidation therapy with ASCT, and obinutuzumab maintenance for three years.
Lyma-101 found acceptable toxicity, good OS, and PFS. Though longer-term follow up is still ongoing. Prof. Rule also mentioned Window I/II, a trial with ibrutinib and rituximab induction, followed by a short intensive chemo-immunotherapy course. He also talked about studies assessing the combination of lenalidomide and rituximab, or obinutuzumab, venetoclax and ibrutinib in older patients.
In his concluding remarks, Prof. Rule stressed the significance of ibrutinib treatment for most patients with relapsed MCL, and recommended it as a standard of care. When questioned, Prof. Rule highlighted his preferred maintenance regimens: in younger patients, rituximab maintenance given after chemo or allo-SCT, in older patients, rituximab maintenance should only be considered after R-CHOP, but not after R-Benda due to a lack of benefit.