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Department of Lymphoma and Myeloma
The University of Texas MD Anderson Cancer Center
Michael Wang MD, has disclosed that he has received consulting fees from AstraZeneca/Acerta, BeiGene, Celgene, Guidepoint Global, InnoCare, Janssen, Juno, Kite, Loxo, Oncternal, Omi, Pharmacyclics, Pulse, Targeted Oncology, and VelosBio and funds for research support from AstraZeneca/Acerta, BeiGene, BioInvent, InnoCare, Janssen, Juno, Kite, Lilly, Loxo, Molecular Templates, Oncternal, Pharmacyclics, VelosBio, and Verastem.
The CAR T‑cell immunotherapy era continues to expand. In the past year, we have had another FDA approval of a CAR T-cell therapy, with several other products rapidly nearing approval. The 2020 ASH annual meeting will again host an impressive number of presentations detailing clinical research into this therapeutic modality. In this commentary, I discuss several recent advances in the field of CAR T‑cell therapy and provide a preview of some of the exciting research that will be presented at ASH 2020.
Lisocabtagene maraleucel (liso-cel) is an anti-CD19 CAR T-cell product that has been investigated in the pivotal phase I TRANSCEND NHL 001 study in patients with relapsed/refractory large B-cell lymphomas. Data from this study have been very exciting, demonstrating impressive efficacy and a toxicity profile that may be improved compared with similar products (although there are no data from comparative clinical trials). Among current investigational CAR T-cell therapies, liso-cel is probably the closest to outpatient therapy in the future. Unfortunately, the FDA review of the liso-cel application was delayed due to COVID-related issues; we recently learned that it will not be completed by the Prescription Drug User Fee Act action date of November 16, 2020.
More exciting data on liso‑cel will be presented at ASH 2020; of particular interest will be an analysis of efficacy and safety in patients with relapsed/refractory mantle cell lymphoma (MCL) in TRANSCEND NHL 001.
Perhaps nothing has changed the way we treat MCL like the recent approval of brexucabtagene autoleucel (KTE-X19), a CD19-directed autologous CAR T-cell immunotherapy. In the past, patients with relapsed/refractory MCL would endure increasingly aggressive therapies, typically with limited success. However, in July 2020, brexucabtagene autoleucel was approved for patients with relapsed/refractory MCL based on data from the phase II ZUMA-2 trial, which demonstrated an ORR of 93% and a CR rate of 67% in this population. Those data were presented at ASH 2019, when the median follow-up was 12 months. At ASH 2020, I will present data from a longer follow-up showing consistent efficacy—with a median follow-up of 17.5 months, the ORR and the CR rate are relatively unchanged.
The approval of brexucabtagene autoleucel represented a paradigm shift for the treatment of MCL; we now have a CAR T‑cell therapy capable of rescuing some terminally sick patients, including those with high Ki67 and p53 mutations. This is a meaningful advance that will save many lives.
Data from numerous other studies of approved and emerging CAR T-cell therapies will be presented at ASH 2020. Several BCMA-targeted CAR T-cell therapies are now in clinical development for patients with relapsed/refractory multiple myeloma. At ASH 2020, we will see data from several analyses of idecabtagene vicleucel from the pivotal KarMMa study. Idecabtagene vicleucel has already been the subject of a successful phase I study and is now being evaluated in several other studies, including the randomized phase III KarMMa-3 trial in patients with relapsed/refractory multiple myeloma. We will also see new data with the BCMA-targeted agents orvacabtagene autoleucel (from the EVOLVE study) and ciltacabtagene autoleucel (from the CARTITUDE-1 study).
CAR T-cell therapy continues to evolve, with exciting novel therapies targeting molecules beyond CD19 and BCMA, including CD20, CD22, ROR1, CD70, and others. Additional strategies in clinical development include CAR T-cell cocktails, as well as dual and bispecific CARs. Although the currently approved CAR T-cells are autologous therapies, which demand an extensive amount of time, labor, and expense, investigations are ongoing with allogeneic CAR T-cells, which may simplify the process. Therefore, we could have off‑the‑shelf CAR T-cells rather than preparing everything from scratch for each patient.
What new data on CAR T-cell therapy are you most looking forward to at ASH 2020? Answer the polling question and join the conversation by posting a comment in the discussion section.
For more on CAR T-cell therapy advances, register here to attend a live Webinar at ASH 2020 on December 4 featuring my colleagues Renier J. Brentjens, MD, PhD; Frederick L. Locke, MD; and Noopur Raje, MD, titled “A Fresh Look at CAR T-Cell Therapy: Recent Advances, New Evidence, and Evolving Paradigms.”