Irene Urbino, MD, Città della Salute e della Scienza di Torino, Turin, Italy discusses the efficacy of blinatumomab given as consolidation in adults with B-cell precursor acute lymphoblastic leukemia (B-ALL). Dr Urbino describes how, in this real-world evidence study, patients with B-ALL were divided into three subgroups – those in first complete remission (CR1), those in second CR after chemotherapy-base salvage therapy (CR2), and those in overt relapse (R/R). The results of the study highlight that blinatumomab should preferably be used in consolidation rather than as salvage therapy in patients with B-ALL in first relapse. This interview took place at the European Hematology Association (EHA) Congress 2022 held in Vienna, Austria.
Jayastu Senapati, MBBS, MD, MD Anderson Cancer Center, Houston, TX, discusses the results of a Phase II study investigating the use of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive (Ph+ALL) and negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) who are measurable residual disease (MRD)-positive. Whilst the study reported promising overall response rates (ORR), it did not meet its primary endpoint. This interview took place at the European Hematology Association (EHA) Congress 2022 held in Vienna, Austria.
Petri Pölönen, PhD, St. Jude’s Research Hospital, Memphis, TN, discusses the results of a study which used whole genome sequencing (WGS), whole exome sequencing (WES), and transcriptome sequencing to characterize the genome of pediatric patients with T-cell acute lymphoblastic leukemia (T-ALL). Dr Pölönen highlights novel T-ALL driver genes and genomic alterations that were identified. This interview took place at the European Hematology Association (EHA) Congress 2022 held in Vienna, Austria.
Bijal Shah, MD, Moffitt Cancer Center, Tampa, FL, provides an overview of two-year follow up results from the Phase III ZUMA-3 trial (NCT02614066) evaluating brexucabtagene autoleucel (brexu-cel), an autologous anti-CD19 CAR-T cell therapy approved in the US, to treat adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In this interview, Dr Shah discusses outcomes with longer follow-up in these patients and in a larger pooled analysis of Phase I and II patients who received the pivotal dose of brexu-cel. Dr Shah also comments on the impact of tumor burden and age on toxicity, and further discusses the future of CAR-T therapy for the treatment of B-ALL. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.
Following a fantastic day at the 4th International Workshop on CAR-T (iwCAR-T) 2022 in Tampa, FL, leading experts David Maloney, MD, PhD, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA, John Gribben, MD, DSc, FRCPath, FMed Sci, Barts and The London School of Medicine, Queen Mary University of London, London, UK, and Noelle Frey, MD, MSCE, University of Pennsylvania, Philadelphia, PA, share their highlights from the leukemia and lymphoma sessions. To begin with, the experts discuss the past, present, and future of CAR-T therapy in acute lymphoblastic leukemia (ALL), outlining strategies to improve relapse-free survival (RFS) in these patients. They then comment on the key challenges to CAR-T therapy in acute myeloid leukemia (ALL) and highlight recent progress in this field. Finally, Dr Maloney, Dr Frey, and Prof. Gribben provide an overview of recent advances in CAR-T therapy for chronic lymphocytic leukemia (CLL), discussing the potential of ibrutinib in modulating the immune microenvironment and improving T-cell fitness in both CLL and in lymphoma, and emphasize the importance of determining the optimal window of opportunity for CAR-T in CLL.
In this video, Mohamad Mohty, MD, PhD, Saint-Antoine Hospital, Paris, France, discusses the efficacy of antibody-drug conjugates (ADCs) for the treatment of multiple myeloma. Prof. Mohty first mentions that ADCs have been approved in other hematological indications, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and Hodgkin lymphoma (HL). Following this, Prof. Mohty discusses the efficacy of ADCs and the promising results observed with the use of belantamab mafodotin for patients who are refractory to other lines of therapy. To conclude, Prof. Mohty explains the need to further investigate the best way to combine ADCs, and manage side effects such as keratopathy. This interview took place at the 8th World Congress on Controversies in Multiple Myeloma (COMy) 2022, held in Paris, France.
Roman Galetto, PhD, Cellectis, Paris, France, briefly discusses some novel allogeneic chimeric antigen receptor T-cell (CAR-T) therapies in the pipeline at Cellectis. Dr Galetto highlights the products being developed for the treatment of various hematological indications, including B-cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML), multiple myeloma, and other B-cell malignancies. This interview took place at the 8th World Congress on Controversies in Multiple Myeloma (COMy) 2022, held in Paris, France.
The use of chimeric antigen receptor (CAR) T-cell therapy in T-cell malignancies have been previously limited due to shared antigens and subsequent fratricide. LaQuisa Hill, MD, Texas Children’s Hospital, Houston Methodist Hospital, Houston, TX, provides an overview of the developments made within the field. Anti-CD5 and -CD7 CAR T-cell therapies have proven to be promising treatments for patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LBL). Anti-CD30 therapies have additionally demonstrated efficacy in patients with peripheral T-cell lymphoma (PTCL) and a favorable safety profile with fewer cases of cytokine release syndrome and neurotoxicity. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Michael Bishop, MD, University of Chicago, Chicago, IL, describes advances in chimeric antigen receptor (CAR) T-cell therapy for hematologic malignancies. Data from the JULIET (NCT02445248), TRANSFORM (NCT03575351), BELINDA (NCT03570892), ZUMA-1 (NCT02348216), and ZUMA-7 (NCT03391466) trials have demonstrated CAR T-cell therapy as a promising frontline therapy in non-Hodgkin lymphoma. Dr Bishop additionally highlights updates in multiple myeloma and acute lymphoblastic leukemia (ALL), as well as strategies to manage CAR T-cell toxicity. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Crystal Mackall, MD, Stanford University, Stanford, CA, explains the rationale and the results from a Phase I trial investigating the safety and efficacy of a bispecific chimeric antigen receptor (CAR) T-cell targeting CD19 and CD22 in combination with chemotherapy in adult patients with recurrent or refractory B-cell malignancies (NCT03233854). Previous studies have revealed that up to two thirds of patients treated with CAR T-cell therapy relapse because of antigen modulation, either by complete loss or by downregulation of the CD19 target antigen. Monospecific CD22-directed CAR T-cells developed to overcome that challenge have shown remarkable activity in antigen loss variants of leukemia and in patients with lymphoma who have progressed after CD19-targeting CAR T-cell therapy. However, the bispecific CAR T-cells targeting both CD19 and CD22 tested in the Phase I trial were not more effective than monospecific CAR T-cells and showed good potency on CD19 but not on CD22. It is thus important to design novel strategies to deliver bispecific CAR T-cells. This interview took place during the 36th Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, D.C.