Mantle Cell Lymphoma: First-line Therapy in Patients Not Eligible for Stem Cell Transplantation

Abstract

Mantle cell lymphoma is a distinct subtype of non-Hodgkin's lymphoma, which has historically been associated with a poor prognosis. It is now recognized as a heterogeneous disease with variable biologic and clinical behavior. Treatment paradigms have evolved along two lines. Younger, fit mantle cell lymphoma (MCL) patients are generally treated with intensive strategies and older less fit patients with non-intensive strategies. Most of the published literature has focused on intensive strategies, which appear to result in more durable remissions, but with an unclear impact on overall survival. The literature is more sparse for the roughly 50% of patients who are not candidates for intensive strategies, and no "standard" approach has been established for this patient population. However, clues are emerging. Randomized clinical trials have (a) established that bendamustine-rituximab (BR) is more efficacious and less toxic than rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); (b) established that bortezomib should replace vincristine if using an R-CHOP backbone; and (c) established that maintenance rituximab (MR) is beneficial after an R-CHOP induction. In our opinion, it is reasonable to extrapolate the data supporting MR after R-CHOP and apply MR after a BR induction. In our practice, we recommend BR followed by MR for 2 years to MCL patients not eligible for intensive therapy. An ongoing US intergroup trial is testing the addition of bortezomib to the BR backbone and the addition of lenalidomide to MR. This trial may establish a standard of care in the older MCL population. In addition, exciting options for relapsed MCL have emerged in the last few years, with the introduction of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and the development of the lenalidomide-rituximab combination. In this article, we will discuss the current available options for these older MCL patients and the evidence supporting those options.

Walking a tightrope: clinical use of ibrutinib in mantle cell lymphoma in the elderly

“…However, in the absence of contraindications, they usually receive rituximab plus a chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]; bendamustine; or other drugs), with possible rituximab maintenance for 2 years after CHOP (the role of rituximab maintenance after bendamustine is still controversial 9 ). 1,10 Unfortunately, the majority of elderly MCL patients will relapse and then have a very poor prognosis. Managing relapsing or refractory (r/r) MCL is particularly challenging because these individuals often have a reduced performance status and are particularly prone to experience treatment-related adverse events (AEs) as a result of previous chemotherapies and increased age.…”

Intensive induction regimens after deferring initial therapy for mantle cell lymphoma are not associated with improved survival

“…A variety of regimens have been utilized including low and high‐intensity treatments with and without autologous hematopoietic stem cell transplantation (ASCT). 20,22‐27 We evaluated the outcomes of patients with MCL who defer initial therapy to determine the impact of induction treatment intensity. Additionally, we describe the patient, disease, and treatment characteristics associated with choice of treatment and identify possible predictors of survival in patients who defer therapy.…”