Articles

Videos

American Society of Hematology (ASH)

“There are estimates that a small number, less than 20%, of patients who are currently CAR T-cell eligible in myeloma actually have access. It's really the minority of people that have access, so just having another therapy on the market will really bridge the gap of some of these access deficiencies.”

Data from the phase 1/2 CARTITUDE-1 study (NCT03548207) demonstrated ciltacabtagene autoleucel’s (cilta-cel) continued ability to produce deep and durable responses in heavily-pretreated patients with multiple myeloma.

Thomas G. Martin, MD, clinical professor of medicine, Adult Leukemia and Bone Marrow Transplantation Program, and associate director, Myeloma Program, University of California San Francisco, and co-leader, Cancer Immunology & Immunotherapy Program, Helen Diller Family Comprehensive Cancer Center, presented these data at the 63rd Annual American Society of Hematology (ASH) Meeting, December 11-14, 2021.

Data on cilta-cel from the CARTITUDE-2 study (NCT04133636) as an earlier line of therapy in patients with only 1 to 3 prior lines of therapy were also presented at ASH 2021. Investigators found that progression-free survival (PFS) at 6 months was 90% (95% CI, 65.6–97.4).

spoke with Martin to learn more about cilta-cel and the current landscape of CAR T-cell therapies. He discussed access issues with CAR T-cell therapies and how adding new therapies to the treatment landscape may improve these issues.

 for the treatment of adult patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy on February 28, 2022.)

1. New data from CARTITUDE-1 Study show continued deep and durable responses of ciltacabtageneautoleucel (cilta-cel) in treatment of heavily pretreated patients with multiple myeloma. News release. Janssen. December 12, 2021. https://www.janssen.com/new-data-cartitude-1-study-show-continued-deep-and-durable-responses-ciltacabtagene-autoleucel-cilta
2. Martin T, Usmani SZ, Berdeja JG, et al. Updated results from CARTITUDE-1: Phase 1b/2 study of CiltacabtageneAutoleucel, a B-cell maturation antigen–Directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. Presented at: 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 549.
3. Cohen YC, Cohen DA, Delforge M, et al. Efficacy and safety of ciltacabtageneautoleucel (cilta-cel), a B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapy, in lenalidomide-refractory patients with progressive multiple myeloma after 1–3 prior lines of therapy: Updated results from CARTITUDE-2. Presented at: 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 3866.

The clinical professor of medicine, Helen Diller Family Comprehensive Cancer Center, UCSF, discussed potential effects of cilta-cel's approval. 

Improving Access to CAR T-Cell Therapies: Thomas G. Martin, MD 

“Once there's sufficient data with this new dosing schema, then hopefully that data will then be evaluated, published and presented. If it looks reasonable enough, that could be how this drug will be packaged to the FDA for hopefully getting it licensed in the future.”

The antithrombin-targeted, siRNA therapeutic fitusiran reduced bleeding in people with hemophilia A or B with or without inhibitors treated with prophylactic doses compared with those only given on-demand treatment.

Fitusiran was evaluated in the phase 3 ATLAS-INH study (NCT03417102), data from which were presented at the 63rd Annual American Society of Hematology (ASH) Meeting, December 11-14, 2021, by Guy Young, MD, director, Hemostasis and Thrombosis Program, Children’s Hospital of Los Angeles and professor of Pediatrics, Keck School of Medicine, University of Southern California.

Fitusiran reduced bleeding to 0 bleeding events in most patients in the fitusiran arm with both hemophilia A and B (n = 25; 65.8%) after treatment. Primary endpoints were met, as these patients achieved statistical significance in reduced annual bleeding rate (ABR) of treated bleeds as well as a reduction in all, spontaneous, and joint bleeds. Higher physical health domain and health-related quality of life scores were also observed in participants treated with fitusiran (both 

 <.0001). Adverse events (AEs) were common and 17.1% (n = 7) of patients reported serious AEs.

 spoke with Young to learn more about the safety profile of fitusiran and how investigators are mitigating these AEs by modifying trial protocols. He discussed how mitigation strategies should be employed in the future if the candidate comes to market.

Young G, Srivastava A, Kavkli K, et al. Efficacy and safety of fitusiran prophylaxis, an siRNA therapeutic, in a multicenter phase 3 study (ATLAS-INH) in people with hemophilia A or B, with inhibitors (PwHI). Presented at: 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 4.

The director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles discussed mitigation strategies in trials and clinic. 

Managing Safety in Fitusiran Treatments of Hemophilia: Guy Young, MD 

Ciltacabtagene autoleucel (cilta-cel) produced deep and durable responses in heavily-pretreated patients with multiple myeloma, according to data from the phase 1/2 CARTITUDE-1 study (NCT03548207).

63rd Annual American Society of Hematology (ASH) Meeting, December 11-14, 2021

, by Thomas G. Martin, MD, clinical professor of medicine, Adult Leukemia and Bone Marrow Transplantation Program, and associate director, Myeloma Program, University of California San Francisco, and co-leader, Cancer Immunology & Immunotherapy Program, Helen Diller Family Comprehensive Cancer Center.

Also presented at ASH 2021 were results from the CARTITUDE-2 study (NCT04133636) which is evaluating cilta-cel as an earlier line of therapy in patients with only 1 to 3 prior lines of therapy.

 Progression-free survival (PFS) at 6 months was 90% (95% CI, 65.6–97.4).

 spoke with Martin to learn more about the CARTITUDE-1 and CARTITUDE-2 studies. He discussed positive safety and efficacy data seen in both studies and cilta-cel's place in the multiple myeloma treatment landscape.

The clinical professor of medicine, Helen Diller Family Comprehensive Cancer Center, UCSF, discussed data from both the CARTITUDE-1 and CARTITUDE-2 studies. 

Cilta-Cel in the Multiple Myeloma Treatment Landscape: Thomas G. Martin, MD 

This content originally appeared on our sister site, 

ARU-1801, an investigative cell therapy from Aruvant Sciences, has been safe and efficacious in 3 adults with severe sickle cell disease (SCD) through 1 year of follow-up post-transplant.

Data presented from the phase 1/2 study (NCT02186418) were presented at the 

American Society of Hematology (ASH) 2021 Meeting

 demonstrated significant improvements in annualized vaso-occlusive events and stabilized anti-sickling globins (HbF). There were no treatment-related serious adverse events in 4 treated patients between the ages of 19 and 35.

Investigators now believe the investigative therapy may serve as a “promising alternative” to myeloblative transplants for patients with severe sickle cell disease who need to achieve durable disease mitigation responses from therapy.

 during ASH 2021, investigator Michael Grimley, MD, of the Division of Bone Marrow Transplantation and Immune Deficiency at Cincinnati Children's Hospital Medical Center, discussed the new phase 1/2 findings and their implication for the future of sickle cell disease care.

“I think this field is almost untapped, as to where we’re going,” Grimley said. “Unfortunately, there’s a very large group of patients who could benefit from a change in their sickle cell care.”

Grimley also discussed plans for the continued trial, which include increasing the patient population to 10 adults before progressing to a regulatory licensing application trial, which could help investigators decrease the age of eligibility to include pediatric children aged ≥12 years old with sickle cell disease.

As he noted, there’s suggestion that younger patients may have better, even safer benefit from the stem cell transplant therapy—and the effort would help to sooner address severe sickle cell disease cases.

“That’s not a stretch to think this therapy may be even more effective in the younger patients, but it has been safe across the board from 18-35 and efficacious for all age ranges,” Grimley said. “But all of us would love to prevent sickle cell complications, instead of treating them after they have sickle cell complications.”

Safety and Efficacy of Aru-1801 in Patients with Sickle Cell Disease: Early Results from the Phase 1/2 Momentum Study of a Modified Gamma Globin Gene Therapy and Reduced Intensity Conditioning

The medical director of Bone Marrow Transplantation and Immune Deficiency at Cincinnati Children's discussed data on ARU-1801 presented at ASH 2021.

Expanding Study Populations of Cell Therapy in Sickle Cell Disease: Michael Grimley, MD

“We had a decent number of patients with hemophilia B with inhibitors in the study. That is a very small population in the United States, roughly 150 patients. These patients have no good alternatives to preventing bleeding and few alternatives to treating bleeding. That's the group of patients that continues to really suffer and has been left behind... by the innovations we've had with emicizumab and factor therapy in hemophilia A.”

Findings from the phase 3 ATLAS-INH study (NCT03417102) of fitusiran were presented at the 63rd Annual American Society of Hematology (ASH) Meeting, December 11-14, 2021, by Guy Young, MD, director, Hemostasis and Thrombosis Program, Children’s Hospital of Los Angeles and professor of Pediatrics, Keck School of Medicine, University of Southern California. Fitusiran reduced bleeding in people with hemophilia A or B with or without inhibitors compared with those only given on-demand treatment. The siRNA therapeutic targets antithrombin and is administered in monthly, prophylactic doses.

Most participants in the study (65.8%) with both hemophilia A and B had treated bleeding events reduced to 0. In general, treated participants also had higher physical health domain health-related quality of life scores (both 

 spoke with Young to learn more about fitusiran and how the siRNA therapeutic may improve outcomes in hemophilia A and B. He discussed unmet needs in hemophilia B and the decent population included in the ATLAS-INH study.

The director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles discussed advantages of the siRNA therapeutic. 

Improving Outcomes in Hemophilia With Fitusiran: Guy Young, MD 

“In my mind, these [data from CARTITUDE-1] were the best results that have ever been shown in this truly triple-class refractory, 6 prior lines of therapy population. This is the most aggressive and the most responsive and efficacious therapy, as a single agent in refractory multiple myeloma treatment, that we've ever seen.”

Ciltacabtagene autoleucel (cilta-cel) produced deep and durable responses in heavily-pretreated patients with multiple myeloma, according to data from the phase 1/2 CARTITUDE-1 study (NCT03548207) presented at the 

Investigators found that the 97 participants treated with cilta-celin the CARTITUDE-1 study had an overall response rate of 98% and that of 61 evaluable participants with minimal residual disease, the progression-free survival rate at 2 years was 100%. Also presented at ASH 2021 were positive results in a less-pretreated population.

 spoke with Martin to learn more about the data from CARTITUDE-1 presented at ASH 2021. He discussed the positive results and cilta-cel's potential in this population.

1. New data from CARTITUDE-1 Study show continued deep and durable responses of ciltacabtageneautoleucel (cilta-cel) in treatment of heavily pretreated patients with multiple myeloma. News release. Janssen. December 12, 2021. 

https://www.janssen.com/new-data-cartitude-1-study-show-continued-deep-and-durable-responses-ciltacabtagene-autoleucel-cilta


2. Martin T, Usmani SZ, Berdeja JG, et al. Updated results from CARTITUDE-1: Phase 1b/2 study of CiltacabtageneAutoleucel, a B-cell maturation antigen–Directed chimeric antigen receptor T cell therapy, in patients with relapsed/refractory multiple myeloma. Presented at: 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 549.
3. Jakubowiak A, Usmani SZ, Berdeja JG, et al. Efficacy and safety of ciltacabtageneautoleucel in patients with relapsed/refractory multiple myeloma: CARTITUDE-1 subgroup analysis. Presented at: 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 3938.

The clinical professor of medicine, Helen Diller Family Comprehensive Cancer Center, UCSF, discussed data from the CARTITUDE-1 study presented at ASH 2021. 

Cilta-Cel's Efficacy in Heavily Pretreated Patients With Multiple Myeloma: Thomas G. Martin, MD 

The first patient has been enrolled in the phase 1/2 CEDAR trial (NCT04819841) of GPH101 (Graphite Bio), an investigative Cas9-edited autologous CD34+ cell therapy for the treatment of 

“GPH101 is the first investigational therapy to enter clinical development that uses our next-generation gene editing platform technology to directly correct the mutation in the beta-globin gene that causes sickle cell disease,” Josh Lehrer, MD, chief executive officer, Graphite Bio, said in a statement.

 “Using our gene correction approach, we have demonstrated in preclinical studies an ability to decrease the production of harmful sickle hemoglobin and restore the expression of normal adult hemoglobin. This approach has the potential to restore normal physiology and is viewed as the gold standard for curing sickle cell disease. We are thrilled that our first patient is now enrolled in our CEDAR clinical trial, and we look forward to evaluating GPH101’s potential as we continue to advance its development with urgency in hopes of delivering a curative therapy to the sickle cell community.”

The hematopoietic stem cell (HSC) therapy GPH101 is developed using Graphite’s next-generation targeted gene integration platform. The platform uses Cas9 technology and a non-integrating DNA template to correct the mutation in the β-globin gene through the homology directed repair (HDR) cellular pathway.

The State of Gene and Cell Therapy for Sickle Cell Disease

Further details on the phase 1/2 trial were presented at the 

63rd Annual American Society of Hematology (ASH) Meeting, December 11-14, 2021,

 by investigator Julie Kanter, MD, associate professor of medicine and co-director, Comprehensive Sickle Cell Center, University of Alabama at Birmingham.

“While allogeneic transplant is the only available cure for sickle cell disease, the procedure has several limitations, mainly lack of available donors and risk of graft-versus-host disease. Other available therapies are considered palliative as they do not specifically reverse end-organ damage. This type of gene therapy – reducing sickle hemoglobin production at the same time as restoring adult hemoglobin expression through direct gene correction – would be an ideal curative option in sickle cell disease,” Kanter said in a statement.

 “As an investigator in the CEDAR trial, I look forward to assessing GPH101’s potential to be a curative option for patients.”

Kanter discussed the CEDAR trial, which is an open-label, single-dose, multi-site trial that plans to enroll around 15 participants with severe SCD. She presented the GPH101 treatment process, from local stem cell selection and cryopreservation to shipment to a central manufacturing facility. 

The CEDAR trial is primarily evaluating the safety of GPH101 by measuring overall survival, mortality, adverse event incidence, and HSC engraftment. Secondary outcomes include pharmacodynamics and measures of exploratory efficacy such as levels of HbA, HbS, and total hemoglobin, as well as clinical manifestations of SCD such as vaso-occlusive events and acute chest syndrome. The trial will also assess changes in organ function, red blood cell health, and gene correction. Graphite expects to dose the first patient in the first half of 2022 with preliminary data available by the end of 2022.

“Sickle cell disease is a devastating illness for which a cure is desperately needed. By directly correcting the mutation that causes sickle cell disease, we believe that GPH101 has the potential to be a one-time cure that restores normal physiology and alleviates the life-threatening morbidities associated with the disease,” Lehrer added to a more recent statement.

 “We are excited to share details about our CEDAR clinical trial for GPH101, in which we recently enrolled our first patient, and we look forward to continuing to advance GPH101’s development in anticipation of sharing initial proof-of-concept data by the end of next year.”

1. Graphite Bio enrolls first patient in phase 1/2 clinical trial of GPH101 for sickle cell disease. News release. Graphite Bio. November 17, 2021. 

https://www.businesswire.com/news/home/20211117005527/en/Graphite-Bio-Enrolls-First-Patient-in-Phase-12-Clinical-Trial-of-GPH101-for-Sickle-Cell-Disease


2. Kanter J, DiPersio JF, Leavey P, et al. Cedar trial in progress: A first in human, phase 1/2 study of the correction of a single nucleotide mutation in autologous HSCs (GPH101) to convert HbS to HbA for treating severe SCD. Presented at: 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 1864
3. Graphite Bio presents overview of phase 1/2 CEDAR Trial evaluating investigational gene editing therapy GPH101 in sickle cell disease at 63rd ASH Annual Meeting and Exposition. News release. Graphite Bio. December 11, 2021. https://www.businesswire.com/news/home/20211211005014/en/Graphite-Bio-Presents-Overview-of-Phase-12-CEDAR-Trial-Evaluating-Investigational-Gene-Editing-Therapy-GPH101-in-Sickle-Cell-Disease-at-63rd-ASH-Annual-Meeting-and-Exposition

Details on the phase 1/2 CEDAR trial were presented at the 2021 ASH meeting. 

Sickle Cell Disease Cell Therapy Clinical Trial Enrolls First Patient 

“We're looking for treatments that reduce the treatment burden. We can do that 1 of 2 ways. One is by the mode of administration... Subcutaneous is a lot easier than IV...The other treatment burden issue is the frequency. Rather than having to have treatment1 to 2 to 3 times per week, we'd like to be able to administrate less often... Fitusiran is once per month in the ATLAS-INH study, and in the future we’ll explore other possible dosing regimens.”

Monthly prophylactic doses of fitusiran, an siRNA therapeutic targeting antithrombin, reduced bleeding in people with hemophilia A or B with or without inhibitors compared with those only given on-demand treatment.

These findings, from the phase 3 ATLAS-INH study (NCT03417102), were presented at the

 63rd Annual American Society of Hematology (ASH) Meeting, December 11-14, 2021

, by Guy Young, MD, director, Hemostasis and Thrombosis Program, Children’s Hospital of Los Angeles and professor of Pediatrics, Keck School of Medicine, University of Southern California.

Young and colleagues found that 65.8% of treated patients with both hemophilia A and B had treated bleeding events reduced to 0. In general, treated participants also had higher physical health domain health-related quality of life scores (both P <.0001).

 spoke with Young to learn more about unmet needs in people with hemophilia. He discussed treatment adherence issues with IV factor therapy and how less frequent fitusiran treatments could reduce patients’ treatment burden.

The director of the hemostasis and thrombosis program at Children’s Hospital Los Angeles discussed improving outcomes in hemophilia with fitusiran. 

Reducing Treatment Burden in Hemophilia: Guy Young, MD 

The phase 3 ALLELE study (NCT03394365) has demonstrated tablecleucel’s (tab-cel; Atara Biotherapeutics) efficacy in patients with Epstein-Barr virus-associated post-transplant lymphoproliferative disease (EBV+ PTLD).

Data from the study showed clinically meaningful improvements in overall response rate (ORR) with promising overall survival (OS) rates and were presented at the American Society of Hematology 2021 Meeting, December 11-14, by Susan Prockop, MD, pediatric oncologist/hematologist, program director, Clinical and Translational Research, Boston Children’s Hospital. (Prockop is formerly of Memorial Sloan Kettering [MSK], an ALLELE trial site).

Tab-cel is also being evaluated in the phase 2 ATA129-EBV-205 study (NCT04554914) in a variety of immunodeficiency associated, EBV-driven conditions, as well as liquid tumors and solid tumors.

 spoke with AJ Joshi, MD, chief medical officer, Atara Biotherapeutics, to learn more about further research being conducted with tab-cel. He stressed the importance of tab-cel being the first allogeneic T-cell immunotherapy to be submitted to a regulatory agency

1. Atara Biotherapeutics to present eight abstracts at the 63rd American Society of Hematology (ASH) Annual Meeting, including first presentation of Tab-cel® pivotal phase 3 (ALLELE) data. News release. Atara Biotherapeutics. November 4, 2021. https://www.businesswire.com/news/home/20211104005811/en/Atara-Biotherapeutics-to-Present-Eight-Abstracts-at-the-63rd-American-Society-of-Hematology-ASH-Annual-Meeting-Including-First-Presentation-of-Tab-cel%C2%AE-Pivotal-Phase-3-ALLELE-Data
2. Prockop S, Mahadeo KM, Beitinjaneh A, et al. Multicenter, Open-Label, Phase 3 Study of Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Recipients with Epstein–Barr Virus-Driven Post Transplant Lymphoproliferative Disease after Failure of Rituximab or Rituximab and Chemotherapy (ALLELE). Presented at: 63rd Annual ASH Meeting; December 11-14, 2021, Atlanta, GA. Abstract 301.

AJ Joshi, MD, chief medical officer, Atara Biotherapeutics, discussed further research with tab-cel, including study 205. 

Further Research With Tab-Cel in EBV+ Post-Transplant Lymphoproliferative Disease 

spoke with Guenther Koehne, MD, PhD, deputy director and chief of stem cell transplantation, hematologic oncology and benign hematology, Miami Cancer Institute, to learn more about the study of chimeric antigen receptor (CAR) T-cell agents axicabtagene ciloleucel (axi-cel; Yescarta) vs tisagenlecleucel (tisa-cel; Kymriah) in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Koehne discussed new data on CAR T-cell agents. One analysis presented at the 

was a propensity score–matched comparison from the French DESCAR-T registry (NCT04328298) of axi-cel and tisa-cel in patients with relapsed or refractory DLBCL. It is unknown how all CAR T-cell therapies definitively measure up against one another, Koehne adds.

Data from the randomized study showed that axi-cel elicited higher response rates in this population; however, the product was also associated with a higher rate of adverse effects, such as immune effector cell–associated neurotoxicity syndrome and cytokine release syndrome, when compared with tisa-cel, Koehne explains. Furthermore, axi-cel and tisa-cel produced similar overall survival rates, raising questions about how to optimally choose between the 2 therapies, Koehne says.

However, potential strategies may be able to inform which products to use in different patient populations, Koehne adds. For example, tisa-cel could be a strong option for older patients with more comorbidities, and axi-cel might be ideal for younger patients with less aggressive lymphomas, Koehne concludes.

The deputy director and chief of stem cell transplantation at Miami Cancer Institute discussed the study of axicabtagene ciloleucel vs tisagenlecleucel in relapsed or refractory diffuse large B-cell lymphoma.

Conferences