R/R MCL: Treating With CAR-T

Javier Munoz, MD, MS, FACP: I was honored to be 1 of the coauthors of the ZUMA-2 trial published in the New England Journal of Medicine. The inclusion criteria for ZUMA-2 allowed patients to enroll with relapsed/refractory mantle cell lymphoma who had received up to 5 prior therapies, including chemotherapy, a monoclonal antibody, and BTK [Bruton tyrosine kinase] inhibitors, whether ibrutinib or acalabrutinib or both. No question about it, when a patient with relapsed or refractory mantle cell lymphoma has received and failed a BTK inhibitor, the prognosis is very poor. CAR [chimeric antigen receptor] T-cell therapy seems to be able to rescue these patients. Hence, it has the potential to change the therapeutic landscape in mantle cell lymphoma.

If you look at the label for brexucabtagene autoleucel, which is the new name for this CAR T-cell therapy explored in ZUMA-2, it states that it’s approved for adult patients with relapsed/refractory mantle cell lymphoma. This produces a situation in which the label is slightly different from the inclusion criteria for the study. The ZUMA-2 inclusion criteria required prior BTK inhibitor exposure, and the label does not mention prior BTK inhibitor exposure. This is similar to our experience with diffuse large B-cell lymphoma after the approvals occurred for tisagenlecleucel and axi-cel [axicabtagene ciloleucel]. This is a multilayer, multistep process, and sometimes it takes a village to bring these novel therapies to your cancer center. You need to factor in all the variables at hand, including age, comorbidities, social support, proximity to a cancer center for monitoring, and availability of a reliable caregiver.

Studies are showing us that CAR T cells are here to stay when it comes to lymphoma, but there may be some subgroups of patients who may not be able to tolerate this advanced technique. Hence, we need to continue exploring clinical trials for this rare disease.

It is important for me to mention that we welcome KTE-X19 as an addition to the mantle cell lymphoma armamentarium, but it will not necessarily be a good fit for all patients. Hence, we need to continue to develop other options for mantle cell lymphoma. Nevertheless, it goes without saying that we’re clearly excited about the results seen in clinical trials when it comes to CAR T-cell therapies.

Transcript edited for clarity.

Case: A 66-Year-Old Woman With Mantle Cell Lymphoma

History

• A 66-year-old woman diagnosed with mantle cell lymphoma in 2017
• She was treated with rituximab, dexamethasone, cytarabine + carboplatin followed by autologous stem cell rescue; achieved PR;
  • Continued on rituximab maintenance therapy
• In 2019 she experienced clinical relapse and was started on acalabrutinib; achieved SD
   

Currently

• She complains of a 3-month history of intermittent fatigue, nausea and dyspnea on exertion
• PMH: DM, medically controlled
• PE: bilateral submandibular lymphadenopathy; otherwise unremarkable
• Labs: WBC 12 X 109/L, hemoglobin 9.8 gm/dL, plt 90,000/u, LDH 410 U/I, ANC 3100/mm3
• Lymph node biopsy: IHC; cyclin D1+, CD10+, CD20+, CD43+; FISH: t (11;14)
• C/A/P CT scan: widespread lymphadenopathy including bilateral submandibular (2.9 cm, 3.4 cm), 2 left-sided axillary lymph nodes (3.7 cm, 4.1 cm), and lumbar region (5.1 cm)
• PET/CT shows diffuse uptake of 18F-FDG in the submandibular, axillary and lumbar lymph nodes
• Beta-2-microglobulin 4.2 µg/L
• Ann Arbor stage IV; MIPI score 6.6, high risk; ECOG PS 0
• Treatment was started with fludarabine + cyclophosphamide, followed by a single infusion of CAR transduced autologous T cell