Oncology

Mantle Cell Lymphoma

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Reducing Treatment-Related Toxicities in Mantle Cell Lymphoma

patient care perspectives by Julie M. Vose, MD, MBA

Overview

As clinical experience with both established and newer therapies for mantle cell lymphoma (MCL) continues to grow, several opportunities for less toxic treatment are of interest.

Expert Commentary

Julie M. Vose, MD, MBA

Neumann M. and Mildred E. Harris Professor
Chief, Division of Oncology/Hematology
Professor of Medicine
University of Nebraska Medical Center
Omaha, NE

“There may be opportunities to reduce treatment-associated toxicities across the care continuum, from first-line treatments, to maintenance therapies, to treatments for relapsed disease.”

Julie M. Vose, MD, MBA

There may be opportunities to reduce treatment-associated toxicities across the care continuum, from first-line treatments, to maintenance therapies, to treatments for relapsed disease. One way to decrease toxicities is by using a less intensive induction regimen prior to autologous stem cell transplantation (ASCT). At some locations, there are variations in induction regimens involving the use of bendamustine-rituximab. For younger patients with MCL, the goal is to get the disease under the best possible control and to at least consider high-dose chemoimmunotherapy and ASCT. Many studies have used a high-intensity cytarabine-containing regimen for induction. Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) is a very toxic regimen that was once used more widely. It is not clear whether such high intensity is necessary, other than perhaps in patients with blastic disease or central nervous system involvement; and, in those circumstances, one would likely want to choose a different regimen. 

Regarding ASCT, it is still unclear whether it is actually needed; however, many centers continue to perform ASCTs in the first remission. In the post-transplant setting, clinical trials have shown that patients can benefit from rituximab maintenance treatment for up to 3 years. With any maintenance therapy, it is important to consider the potential toxicities as well, so we look out for cytopenias, infections, and other problems that might arise from the maintenance therapy. In the context of the COVID-19 pandemic, questions have arisen with regard to the balance between the benefits of rituximab maintenance and the potential for worsened outcomes due to COVID-19, so this has been an area of uncertainty and controversy during the pandemic.

With respect to relapsed/refractory MCL, there are many different treatment options, probably the most common of which are the Bruton tyrosine kinase (BTK) inhibitors. Different toxicities are associated with different BTK inhibitors, and the choice of which one to use is informed by the individual patient and the patient’s age and comorbidities. Compared with the more recently introduced BTK inhibitors, ibrutinib may carry a higher risk of toxicities such as bleeding and atrial fibrillation. So, if the patient is older, is at risk for atrial fibrillation, or is on anticoagulation therapy, that should be taken into consideration when choosing a BTK inhibitor. If the patient is on warfarin, it is difficult to recommend any of the BTK inhibitors, although these drugs may be considered in those receiving direct oral anticoagulants. Other toxicities associated with BTK inhibitors include arthralgias and myalgias, but bleeding and atrial fibrillation are the biggest concerns. 

References

Brown JR, Moslehi J, O’Brien S, et al. Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials. Haematologica. 2017;102(10):1796-1805. doi:10.3324/haematol.2017.171041

Byrd JC, Owen R, O’Brien SM, et al. Pooled analysis of safety data from clinical trials evaluating acalabrutinib monotherapy in hematologic malignancies. Blood. 2017;130(suppl 1):4326. doi:10.1182/blood.V130.Suppl_1.4326.4326

Lamure S, Dulery R, Delord M, et al. High incidence of persistent COVID-19 among patients with lymphoma treated with B-cell depleting immunotherapy [abstract S09-02]. Abstract presented at: American Association for Cancer Research Virtual Meeting: COVID-19 and Cancer; February 3-5, 2021.

Le Gouill S, Thieblemont C, Oberic L, et al; LYSA Group. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377(13):1250-1260. doi:10.1056/NEJMoa1701769

Merryman RW, Edwin N, Redd R, et al. Rituximab/bendamustine and rituximab/cytarabine induction therapy for transplant-eligible mantle cell lymphoma. Blood Adv. 2020;4(5):858-867. doi:10.1182/bloodadvances.2019001355

Rhodes J, Mato A, Sharman JP. Monitoring and management of toxicities of novel B cell signaling agents. Curr Oncol Rep. 2018;20(6):49. doi:10.1007/s11912-018-0694-x

Villa D, Sehn LH, Savage KJ, et al. Bendamustine and rituximab as induction therapy in both transplant-eligible and -ineligible patients with mantle cell lymphoma. Blood Adv. 2020;4(15):3486-3494. doi:10.1182/bloodadvances.2020002068

Julie M. Vose, MD, MBA

Neumann M. and Mildred E. Harris Professor
Chief, Division of Oncology/Hematology
Professor of Medicine
University of Nebraska Medical Center
Omaha, NE

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