Dr. Goy on the Management of Patients With Genetic Abnormalities and Low Risk in MCL

Andre H. Goy, MD, physician in chief, Hackensack Meridian Health Oncology Care Transformation Service, chairman & chief physician officer, John Theurer Cancer Center, Lydia Pfund Chair for Lymphoma, Academic Chairman Oncology, Hackensack Meridian School of Medicine at Seton Hall University, professor of medicine, Georgetown University, discusses the appropriate monitoring and management of patients with mantle cell lymphoma (MCL) who display genetic abnormalities but are not considered to be high risk.

Due to the variety of genetic features, risk status, and other characteristics across the disease spectrum in MCL, it is important to develop a treatment approach that is specific to a patient’s MCL presentation.

The use of next-generation sequencing in routine clinical practice can best identify patients who carry genetic alterations, do not exhibit high-risk features, and still require treatment in the first line, Goy begins. Traditionally, approaches to management and monitoring in this population have been formulated according to a patient’s ability to tolerate high-dose therapies with or without autologous stem cell transplant (ASCT), Goy explains.

Patients who are younger than 65 years of age and are transplant eligible will typically receive induction therapy with rituximab (Rituxan) and cytarabine followed by ASCT, he says. Conversely, patients who are older than 65 will often undergo frontline treatment with bendamustine plus rituximab (BR) followed by maintenance therapy with rituximab.

The use of frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (Velcade; VR-CAP) has also been explored for this patient population. The regimen has demonstrated a substantial long-term survival benefit and could be an alternative to other standard approaches like rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) or BR induction.

The addition bortezomib to standard BR was also explored for this population in the phase 2 ECOG-ACRIN E1411 trial (NCT01415752). However, the regimen did not meet the primary end point of improved progression-free survival (PFS) or increased responses vs BR alone. Accordingly, BR with rituximab maintenance was supported as the standard induction treatment in this population.

Lastly, data from the prospective, phase 2 study of patients with previously untreated MCL in the MAINTAIN trial (NCT00877214) aimed to confirm the benefit of rituximab maintenance following first-line BR. The trial compared the effect of 2 years of rituximab maintenance vs observation in this population. However, the trial did not show a significant difference in PFS or overall survival between arms. The median PFS was not reached for the rituximab maintenance arm compared with 54.7 months in the observation arm. These inconclusive results indicate that longer follow-up is needed.

Editor’s Note: Dr. Goy reports serving in a consulting or advisory role for AstraZeneca, Elsevier, Gilead Sciences, Janssen, Kite, a Gilead company, OncLive Peer Exchange, Physicans' Education Resource, Resilience Care, Vincera Pharma/Vincerx Pharma; he has employment with OM Pharmaceutical Industries, Regional Cancer Care Associates; he received institutional research funding from Acerta Pharma, AstraZeneca, Celgene, Constellation Pharmaceuticals, Genentech/Roche, Infinity Pharmaceuticals, Infinity/Verastem, Janssen, Karyopharm Therapeutics, Kite/Gilead, Pharmacyclics; he has ownership interests in and serves in a leadership role for COTA, Genomic Testing Cooperative, Resilience Care; he served on a speakers’ bureau for Bristol MyersSquibb/Celgene.