Ibrutinib Maintenance Demonstrates Feasibility Post-Induction Therapy Among Patients With Previously Treated MCL

Maintenance with Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib following induction chemo-immunotherapy with or without autologous stem cell transplantation (autoSCT) was feasible and demonstrated manageable safety among patients with treatment-naive mantle cell lymphoma (MCL), according to findings published in Blood Advances. 

Reem Karmali, MD, Northwestern University Feinberg School of Medicine, Chicago, Illinois, and coauthors aimed to assess the 3-year progression-free survival from the initiation of ibrutinib maintenance as the primary end point of this study. 

A total of 36 eligible patients with MCL who demonstrated a complete or partial response to frontline chemo-immunotherapy with or without autoSCT were administered ibrutinib maintenance at 560 mg daily for up to 4 years. Minimal residual disease (MRD) by next-generation sequencing on peripheral blood was assessed pre-ibrutinib maintenance, and at 1, 6, and 18 to 24 months post-initiation. 

Results indicated that for frontline treatment, 50% of patients (n = 18) had consolidation with autoSCT in the first complete response prior to ibrutinib maintenance. At a median follow-up of 55.7 months, 47% of patients (n = 17) successfully finished the full course of ibrutinib maintenance at a median of 37.5 cycles (range: 2 to 52). The 3-year progression-free survival was 94%, and the 3-year overall survival rate was 97%. Notably, patients who underwent prior autoSCT had a 3-year progression-free survival and overall survival rate of 100%. 
Regarding safety, the most common treatment-related adverse event associated with ibrutinib maintenance was infection, which occurred in 86% of patients (n = 31) and was typically low-grade. The most common grade 3/4 toxicities were hematologic. 

Among the 22 patients assessed for MRD, all were MRD-negative after induction, and 6 became MRD-positive on ibrutinib maintenance. Of these 6 patients, 2 reverted to an MRD-negative status with continued ibrutinib maintenance. All 6 patients maintained radiographic complete responses, except for 1 who experienced disease progression. 

As end points were met, Dr Karmali et al concluded, “[Ibrutinib maintenance] is feasible in MCL after frontline chemo-immunotherapy with manageable toxicities though significant.”

“Changes in [next-generation sequencing]-MRD were noted in limited patients during maintenance with few progression and survival events,” they added. 

Source: 

Karmali R, Abramson JS, Stephens DM, et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. Published online September 27, 2023. doi: 10.1182/bloodadvances.2023011271