Clinical Pearls & Morning Reports
Published June 29, 2022
Initial studies of survival among patients treated for mantle-cell lymphoma showed a poor outcome after standard chemotherapy. However, with the development of rituximab and regimens specific for this disorder, survival has improved. Read the NEJM Review Article here.
Q: Is mantle-cell lymphoma equally common in men and women?
A: Mantle-cell lymphoma accounts for approximately 5 to 7% of all lymphomas. The median age of patients is between 60 and 70 years. Mantle-cell lymphoma has a striking sex imbalance, with approximately 70% of all cases in men. Most patients with mantle-cell lymphoma present with nonlocalized, palpable lymphadenopathy, with or without systemic symptoms. More than 80% have stage III or IV disease at diagnosis, frequently with bone marrow involvement.
Q: What are some of the characteristics of the tumor cells in mantle-cell lymphoma?
A: In nearly all cases, the tumor cells overexpress cyclin D1 (a cell-cycle regulatory protein that drives cells from the G1 phase into the S phase), SOX11 (a transcription factor not normally expressed in B cells that influences the expression of several genes involved in cell survival), and Bcl-2 (an antiapoptosis protein). These changes tend to promote cell survival and proliferation, though the precise mechanism of cell transformation and acquisition of proliferative autonomy is not known.
A: Patients with mantle-cell lymphoma are frequently divided into two groups for initial therapy. One group includes patients who are sufficiently young and healthy to be candidates for consolidative autologous bone marrow transplantation. The other group of patients are considered to be poor candidates for high-dose chemotherapy and autologous transplantation and are instead treated with standard chemotherapy regimens, with or without maintenance rituximab therapy.
A: In most patients with mantle-cell lymphoma, the primary treatment regimen does not result in a cure, and salvage therapy is required. Several new, targeted therapies are active in patients with relapsed or refractory mantle-cell lymphoma. These include the Bruton’s tyrosine kinase inhibitors (irreversible inhibitors: ibrutinib, zanubrutinib, and acalabrutinib; reversible inhibitor: pirtobrutinib), lenalidomide, bortezomib, the mammalian target of rapamycin inhibitors temsirolimus and everolimus, the phosphatidylinositol 3-kinase inhibitors idelalisib and umbralisib, and the Bcl-2 inhibitor venetoclax. These drugs are often given in combination with rituximab or another anti-CD20 antibody. The response rates have been quite high, and when the drugs are used in combination, the complete response rates are frequently in the range of 50%. Both autologous and allogeneic hematopoietic stem-cell transplants have been used for patients with relapsed or refractory mantle-cell lymphoma. Unfortunately, given the advanced age of most patients with mantle-cell lymphoma, only a subgroup of patients are candidates for allogeneic transplantation. New immunotherapies have had a major effect on a number of cancers, including some lymphomas. Unfortunately, inhibition of programmed cell death 1 (PD-1) or the PD-1 ligand seems to be minimally active in mantle-cell lymphoma.