A 66-Year-Old Woman With Mantle Cell Lymphoma - Episode 3
Javier Munoz, MD, MS, FACP: The course of mantle cell lymphoma is many times convoluted. This is an aggressive disease. The median overall survival when incorporating intensive therapy is 8 to 10 years, and shorter survival times are seen with less intensive therapy. For the relapsed/refractory setting of mantle cell lymphoma, there are 3 BTK [Bruton tyrosine kinase] inhibitors currently FDA approved: ibrutinib, acalabrutinib, and zanubrutinib. Other options include bortezomib, the immunomodulator lenalidomide, and the BCL2 inhibitor, venetoclax.
Patients who are relapsed or refractory after a BTK inhibitor have a very ominous prognosis, with a survival of maybe 13 months. Hence, several trials have been conducted trying to salvage this population of patients. The inclusion criteria for ZUMA-2 was for patients with relapsed or refractory mantle cell lymphoma after up to 5 previous therapies, and all patients needed to have received a previous BTK inhibitor. Needless to say, these patients face an unmet need in lymphoma, and the ZUMA-2 trial did allow patients with high-risk features to enroll, including patients with high MKI67, TP53 abnormalities, high MIPI [Mantle Cell Lymphoma Prognostic Index] scores, and blastoid or pleomorphic histologies. These patients are the sickest of the sick and have historically done very poorly with standard chemotherapy.
We know that chimeric antigen receptor, or CAR, T-cell therapy, such as axicabtagene ciloleucel, or axi-cel for short, has displayed efficacy in patients with relapsed or refractory aggressive B-cell lymphomas. This includes diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma. KTE-X19 is an anti-CD19 CAR T-cell therapy, meaning you are re-educating those T cells to target cells that express CD19, which is present across the board in multiple B-cell malignancies including mantle cell lymphoma. The KTE-X19 data in the ZUMA-2 trial was recently presented by Dr Michael Wang at medical conferences. Furthermore, KTE-X19 is particular in the way that it’s produced in a manufacturing process that removes circulating CD19-expressing malignant cells that could potentially be present in patients with leukemia or lymphomas. The removal of these CD19 malignant cells decreases the chances of exhaustion of anti-CD19 CAR-T cells during the manufacturing process, making it more seamless.
ZUMA-2 was a phase 2 trial that analyzed data for 74 patients enrolled. The results showed 93% of patients had an objective response, and 67% of patients had a complete response. KTE-X19 was manufactured for 71 patients and administered to 68 patients. Hence, when you look at the intention-to-treat analysis, the objective response was 85% and complete response was 59%, which is still impressive.
At 12 months, the estimated progression-free survival and overall survival were 61% and 83%, respectively. Very similar to the CAR T cells previously approved for aggressive B-cell lymphomas, serious and life-threatening toxic effects were consistent with those reported with those of other constructs. The main toxicities for CAR T-cell therapies, in general, are cytokine release syndrome and neurological events. Grade 3 or higher cytokine release syndrome and neurological events occurred in 15% and 31% of patients, respectively, when KTE-X19 was used.
Transcript edited for clarity.
Case: A 66-Year-Old Woman With Mantle Cell Lymphoma