Gene-Based Medicine – VJRegenMed

CD33 CRISPR/Cas9 gene-edited donor allograft in patients with AML at risk of relapse post-HSCT

Anya Kerkache — Thu, 09 Mar 2023 11:31:49 +0000

John DiPersio, MD, PhD, Washington University School of Medicine, St. Louis, MO, shares the rationale and results of a first-in-human clinical trial evaluating the safety of trem-cel (formerly VOR33), a CD33 CRISPR/Cas9 gene-edited donor allograft designed to prevent relapse in patients with acute myeloid leukemia (AML) undergoing hematopoietic stem cell transplantation (HSCT; NCT04849910). Results from the first two patients transplanted with trem-cel indicated neutrophil engraftment and a similar platelet recovery when compared to patients who received non-edited CD34-selected grafts. Treatment with gemtuzumab ozogamicin (GO) in one of the recipients did not result in a change in blood counts, suggesting that the target was effectively eliminated on the recipient’s stem cells and that GO would then only target residual leukemia cells expressing CD33. The ability of this strategy to induce long-term remission and to effectively eliminate all residual leukemia cells remains to be confirmed. This interview took place at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR® held in Orlando, FL.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

Outcomes of children and young adults with B-ALL following tisa-cel reinfusion

Anya Kerkache — Thu, 09 Mar 2023 11:31:48 +0000

Kevin McNerney, MD, MSc, Johns Hopkins All Children’s Hospital, St. Petersburg, FL, shares the results of a retrospective study evaluating the safety and efficacy of tisagenlecleucel (tisa-cel) reinfusion in children and young adults with B-cell acute lymphoblastic leukemia (B-ALL). Overall, the study showed that second CAR-T infusions were well tolerated, allowed patients to achieve a complete remission (CR) or re-establish B-cell aplasia (BCA), and could be used as a bridge to transplant. However, most remissions were brief and BCA was limited. This interview took place at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR® held in Orlando, FL.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

Safety and efficacy of LV20.19 CAR-T therapy in Richter’s transformation and R/R MCL

Anya Kerkache — Thu, 09 Mar 2023 11:31:47 +0000

Nirav Shah, MD, Medical College of Wisconsin, Milwaukee, WI, comments on the results of two studies evaluating the LV20.19 CAR-T product in patients with Richter’s transformation and in patients with heavily pretreated mantle cell lymphoma (MCL; NCT04186520). Out of the six patients with Richter’s transformation who were evaluated, four achieved a durable remission and the overall response rate (ORR) was 100%. Patients presented a unique toxicity profile, with a high incidence of hemophagocytic lymphohistiocytosis (HLH)-like toxicity. In MCL, eight of the 14 patients in the study met the primary endpoint, and the ORR at day 90 was 100%. This interview took place at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR® held in Orlando, FL.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

Phase I study of rapcabtagene autoleucel in patients with R/R DLBCL

Anya Kerkache — Thu, 09 Mar 2023 11:31:46 +0000

Nirav Shah, MD, Medical College of Wisconsin, Milwaukee, WI, gives an update on a Phase I study of rapcabtagene autoleucel in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Dr Shah explains that this next-generation CD19 CAR-T therapy has been manufactured using T-Charge, which allows this product to be manufactured faster than other CAR-T therapies, thus helping it to preserve T cell stemness, decrease the dose of infused CAR-Ts, and increase its overall quality. The study identified a safe dose level for further investigations and reported low rates of cytokine release syndrome (CRS). This interview took place at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR® held in Orlando, FL.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

KarMMa-3 results: ide-cel vs standard regimens in triple-class exposed multiple myeloma

Anya Kerkache — Thu, 09 Mar 2023 11:31:45 +0000

In this video, Sergio Giralt, MD, Memorial Sloan Kettering Cancer Center, New York City, NY, gives an overview of the results of the KarMMa-3 study (NCT03651128), a Phase III trial comparing idecabtagene vicleucel (ide-cel) versus standard regimens in patients with triple class–exposed relapsed/refractory (R/R) multiple myeloma. The study reported a significant benefit for ide-cel in terms of complete remission (CR) rate and progression-free survival (PFS) across all risk categories. This interview took place at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR® held in Orlando, FL.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

Preliminary results from Phase I study of CD123 CAR-T therapy in pediatric R/R AML

Anya Kerkache — Thu, 09 Mar 2023 11:31:44 +0000

In this video, Swati Naik, MBBS, St. Jude Children’s Research Hospital, Memphis, TN, discusses the rationale and preliminary results from a Phase I study evaluating the safety and feasibility of CD123-targeting CAR-Ts in pediatric patients with relapsed/refractory (R/R) acute myeloid leukemia (AML; NCT04318678). Dr Naik first explains the challenges associated with designing effective CAR-Ts for AML, including the identification of a suitable target, patient heterogeneity, and the aggressive and immunosuppressive nature of the disease. Dr Naik then comments on the results of the study, which showed evidence of expansion and anti-leukemic activity at different dose levels, with no dose-limiting toxicities. This interview took place at the 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR® held in Orlando, FL.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

CAR-T therapy in acute and chronic leukemias: current applications and future outlooks

Anya Kerkache — Wed, 08 Mar 2023 10:35:19 +0000

John Gribben, MD, DSc, FRCP, FRCPath, FMed Sci, Barts Cancer Institute, London, UK, shares some insights into clinical indications for CAR-T therapy in acute and chronic leukemias, highlighting recent updates and challenges in this space. Prof. Gribben first discusses the role of CAR-T therapy in acute lymphoblastic leukemia (ALL), drawing focus on the two approved products in this malignancy. Prof. Gribben then goes on to explain mechanisms of resistance to CAR-T therapy in ALL, and ongoing research in this space. Following this, Prof. Gribben discusses updates and challenges with the use of CAR-T therapy in T-cell malignancies and acute myeloid leukemia (AML), and concludes by highlighting challenges with developing efficacious CAR-T products for chronic lymphocytic leukemia (CLL), which may be overcome by combining CAR-T cells with Bruton’s tyrosine kinase (BTK) inhibitors. This interview took place at the EBMT-EHA 5th European CAR T-cell Meeting held in Rotterdam, The Netherlands.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

Novel CAR-T constructs emerging for patients with multiple myeloma who experience loss of BCMA

Anya Kerkache — Wed, 08 Mar 2023 10:35:19 +0000

Hermann Einsele, MD, FRCP, University Hospital of Würzburg, Würzburg, Germany, briefly discusses CAR-T constructs emerging for patients with multiple myeloma who experience loss of BCMA, including agents targeting GPRC5D, CD38 and SLAMF7. This interview took place at the EBMT-EHA 5th European CAR T-cell Meeting held in Rotterdam, The Netherlands.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

Exploring the potential role of CD7-targeting CAR-T cells in T-ALL

Anya Kerkache — Wed, 08 Mar 2023 10:35:18 +0000

Maksim Mamonkin, PhD, Baylor College of Medicine, Houston, TX, shares some insights into the promise of CD7-targeting CAR-T therapies for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL). Dr Mamonkin explains methods used to develop these products, and further highlights the promising activity that has been observed in ongoing clinical trials. This interview took place at the EBMT-EHA 5th European CAR T-cell Meeting held in Rotterdam, The Netherlands.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.

The importance of managing hematologic toxicity associated with CAR-T therapy

Anya Kerkache — Wed, 08 Mar 2023 10:35:17 +0000

In this video, Marion Subklewe, MD, Ludwig-Maximilians University of Munich, Munich, Germany, comments on the importance of improving methods of assessing and managing hematologic toxicity associated with the use of CAR-T therapy. Prof. Subklewe also shares some insights into the novel CAR-HEMATOTOX risk stratification tool being evaluated in patients treated with CAR-T therapy for various hematological malignancies. This interview took place at the EBMT-EHA 5th European CAR T-cell Meeting held in Rotterdam, The Netherlands.

These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.