Leukemia – 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.

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.

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.

Challenges with CAR-T therapy in AML & insights into IF-BETTER-gated CAR-T cells

Anya Kerkache — Wed, 08 Mar 2023 10:35:16 +0000

Sascha Haubner, MD, Memorial Sloan Kettering Cancer Center, New York, NY, discusses challenges with developing efficacious CAR-T cell products for the treatment of patients with acute myeloid leukemia (AML), highlighting the heterogeneity of this disease. Dr Haubner then shares some insights into the development of IF-BETTER-gated CAR-T cells, which have demonstrated promising pre-clinical activity and will soon be evaluated in a first-in-human trial. 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 safety and efficacy of UCART123v1.2 in R/R AML: results from AMELI-01

Anya Kerkache — Thu, 26 Jan 2023 12:11:29 +0000

David Sallman, MD, Moffitt Cancer Center, Tampa, FL, discusses the results of the AMELI-01 Phase I trial of UCART123v1.2 in adult patients with relapsed refractory (R/R) CD123+ acute myeloid leukemia (AML; NCT04106076). UCART123v1.2 is an anti-CD123 allogeneic CAR-T product, that has been genetically modified to minimize the occurrence of graft-versus-host disease (GvHD). Overall, results suggest UCART123v1.2 is well tolerated, though severe cytokine release syndrome (CRS) did occur, and that three-drug lymphodepletion optimizes CAR-T expansion and patient responses. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.

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

Results from a Phase I trial of rapidly manufactured Prgn-3006 Ultracar-T in R/R AML

Anya Kerkache — Thu, 26 Jan 2023 12:11:28 +0000

In this video, David Sallman, MD, Moffitt Cancer Center, Tampa, FL, outlines the completed Phase I results for Prgn-3006 Ultracar-T in patients with relapsed/refractory (R/R) CD33+ acute myeloid leukemia (AML). Prgn-3006 Ultracar-T is an autologous CAR-T cell product with decentralized manufacturing that significantly reduces the time between apheresis and CAR-T infusion compared to standard autologous CAR-T therapies. Overall, results suggest that Prgn-3006 Ultracar-T is well tolerated, with only a few grade 3 cytokine release syndrome (CRS) events and no dose-limiting toxicities. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.

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

Results from the first-in-human trial of huCART19-IL18 in patients with R/R NHL and CLL

Anya Kerkache — Thu, 26 Jan 2023 12:11:27 +0000

Jakub Svoboda, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, describes the mechanism of action of huCART19-IL18, a 4th generation autologous CAR T-cell product, and outlines findings from a first-in-human trial investigating the efficacy of huCART19-IL18 in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphomas (NHL) or chronic lymphocytic leukemia (CLL) (NCT04684563). Results from this study so far have been encouraging, with no unexpected toxicities being recorded and some patients already achieving complete response. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.

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