On November 3, 2022 BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a pre-commercial-stage biopharmaceutical company focused on oncology, reported that its full pharmacoeconomic study that indirectly evaluated the cost-effectiveness of using the investigational drug motixafortide as a primary stem cell mobilization (SCM) agent in combination with granulocyte colony stimulating factor (G-CSF), against plerixafor in combination with G-CSF, in multiple myeloma (MM) patients undergoing autologous stem cell transplantation, will be presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting held from December 10-13 in New Orleans, LA (Press release, BioLineRx, NOV 3, 2022, View Source [SID1234622932]). The analysis demonstrated significant net cost savings with motixafortide plus G-CSF and a greater proportion of patients achieving successful mobilization of optimal amounts of stem cells in a single apheresis day. The company has submitted a new drug application to the FDA for motixafortide in this indication.

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Collaborating investigators will also present a Phase 1 trial design of a novel mobilization regimen combining motixafortide and a VLA-4 inhibitor. The clinical trial will evaluate the regimen’s ability to safely produce the significant quantity of hematopoietic stem cells (HSC) required for the genetic manipulation processes used in gene therapy development in patients with sickle cell disease (SCD). Sickle cell disease is one of the most common inherited genetic diseases globally and HSC -based gene therapies now offer curative potential; however, effective HSC-based gene therapy depends on the collection of sufficient HSCs. Currently, the most widely used mobilization strategies include G-CSF and CXCR4 inhibition with plerixafor. However, G-CSF is contra-indicated in SCD and short-acting CXCR4 inhibition with plerixafor alone does not reliably yield optimal HSC numbers for SCD gene therapy applications. Developing novel HSC mobilization regimens to rapidly and reliably mobilize optimal CD34+ HSCs for gene therapy in SCD represents an unmet need.

"We are pleased to publish our full pharmacoeconomic data at ASH (Free ASH Whitepaper) which demonstrates that the combination of motixafortide plus G-CSF significantly lowers healthcare resource utilization in patients with multiple myeloma in the U.S. undergoing autologous stem cell transplantation," said Philip Serlin, Chief Executive Officer of BioLineRx. "Importantly, motixafortide plus G-CSF had significantly greater successful mobilization of the optimal number of cells following a single administration of motixafortide and in only one apheresis session, improving the patient journey. If approved, we believe motixafortide has the potential to become the new standard of care for all patients with multiple myeloma undergoing autologous stem cell transplantation. We are also excited to introduce the design of a Phase 1 study by investigators who are targeting unmet needs in both quantity and quality of cells harvested for cell engineering and administration. Our team is working diligently to develop motixafortide in different areas of stem cell mobilization with the objective of becoming the standard of care in these settings."

Major Findings of Cost-Effectiveness Analysis

The study was performed by the Global Health Economics and Outcomes Research (HEOR) team of IQVIA. For this study, an adjusted indirect comparison was undertaken, using data from the relevant phase 3 trials. This included finding and extracting efficacy data for both motixafortide (from GENESIS Phase 3 trial patient-level data) and plerixafor (aggregate data from literature), estimating plerixafor efficacy as if it had been one arm of the GENESIS trial (Bucher method), and implementing the results in the cost-effectiveness model.

Healthcare resource utilization (HRU) outcomes significantly favored motixafortide plus G-CSF during primary mobilization, including less frequent administration of G-CSF, lower G-CSF doses, and fewer apheresis sessions
The proportion of patients with successful mobilization of≥6×106 CD34+ cells/kg within 1 apheresis day was significantly greater with motixafortide plus G-CSF than with plerixafor plus G-CSF
Motixafortide plus G-CSF was dominant to plerixafor plus G-CSF over a lifetime horizon, resulting in additional QALYs and lower total costs as per base case deterministic results. The key cost drivers were the probability of successful transplantation, long-term maintenance costs, and the time to engraftment in poor mobilizers
PRESENTATIONS AT ASH (Free ASH Whitepaper)

Title: Cost-Effectiveness Analysis of Motixafortide Versus Plerixafor in Stem Cell Mobilization for Autologous Transplantation in Patients with Multiple Myeloma
Presenting Author: Mark Lamotte, MD, Global Health Economics & Outcomes Research, IQVIA
Date/Time: Poster 4848, Monday, December 12, 2022, 6:00 PM – 8:00 PM

Title: A Phase I Safety and Feasibility Study to Evaluate Motixafortide (CXCR4/SDF-1 Inhibition) and Natalizumab (VLA-4/VCAM-1 Inhibition) As a Novel Regimen to Mobilize CD34+ Hematopoietic Stem Cells for Gene Therapy in Sickle Cell Disease
Presenting Author: Zachary Crees, MD, Division of Oncology, Washington University School of Medicine, St. Louis, MO
Date/Time: Poster 4679, Monday, December 12, 2022, 6:00 PM – 8:00 PM

About the GENESIS Trial
The GENESIS trial (NCT03246529) was initiated in December 2017. GENESIS was a randomized, placebo-controlled, multicenter study, evaluating the safety, tolerability and efficacy of motixafortide and G-CSF, compared to placebo and G-CSF, for the mobilization of hematopoietic stem cells for autologous transplantation in multiple myeloma patients. The primary objective of the study was to demonstrate that only one dose of motixafortide on top of G-CSF is superior to G-CSF alone in the ability to mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. A key secondary objective of the study was to demonstrate that only one dose of motixafortide on top of G-CSF is superior to G-CSF alone in the ability to mobilize ≥ 6 million CD34+ cells in only one apheresis session. In this regard, ~90% of patients in the GENESIS study went directly to transplantation after mobilizing the optimal number of stem cells following only one administration of motixafortide on top of G-CSF and in only one apheresis session, compared to less than 10% of those receiving G-CSF alone. Additional objectives included time to engraftment of neutrophils and platelets and durability of engraftment, as well as other efficacy and safety parameters.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects some white blood cells called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells in the bone marrow with tumors. In 2022, it is estimated that more than 34,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.

About Autologous Stem Cell Transplantation
Autologous stem cell transplantation (ASCT) is part of the standard treatment paradigm for a number of blood cancers, including multiple myeloma. In the U.S., nearly 15,000 ASCTs are performed each year with the majority in patients with multiple myeloma. The current standard of care includes the administration of 5-8 daily doses of granulocyte colony stimulating factor (G-CSF), with or without 1-4 doses of plerixafor, and the performance of 1-4 apheresis sessions. For patients unable to mobilize sufficient numbers of cells for harvesting during this primary mobilization phase, rescue therapy is carried out, consisting of 1-4 additional doses of plerixafor on top of G-CSF, and the performance of an additional number of apheresis sessions as necessary. In light of this, an agent with superior mobilization activity may significantly reduce the mobilization and harvesting burden and associated risks of the ASCT process and lead to significant clinical and resource benefits.

On November 3, 2022 Aptose Biosciences Inc. ("Aptose") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics targeting the underlying mechanisms of cancer, reported that clinical data for tuspetinib (formerly HM43239), a myeloid kinome inhibitor, and luxeptinib, a dual lymphoid and myeloid inhibitor, have been accepted for poster presentations at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held Saturday, December 10 – Monday, December 13, 2022 in New Orleans, LA and virtually (Press release, Aptose Biosciences, NOV 3, 2022, View Source [SID1234622931]).

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The abstracts accepted for presentation are listed below and can be viewed online at the ASH (Free ASH Whitepaper) conference website. Note that the actual presentations will include more recent updates and additional data not found in the abstracts. Aptose will hold a Clinical Update webcast during the ASH (Free ASH Whitepaper) timeframe to provide up-to-date data. Details will be forthcoming.

Poster Presentation Details

Publication Number 2758: A Phase 1/2 Dose Escalation Study of the Myeloid Kinase Inhibitor HM43239 in Patients with Relapsed or Refractory Acute Myeloid Leukemia

Publication Number 2767: A Phase 1a/b Dose Escalation Study of the FLT3/BTK Inhibitor Luxeptinib (CG-806) in Patients with Relapsed or Refractory Acute Myeloid Leukemia

Publication Number 2893: A Phase 1a/b Dose Escalation Study of the BTK/FLT3 Inhibitor Luxeptinib in Patients with
The poster abstracts also will be published in the November supplemental issue of Blood, an ASH (Free ASH Whitepaper) journal, available online.

On November 3, 2022 Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on creating and delivering engineered cells as medicines, reported that six abstracts have been accepted for presentation, including two oral presentations, at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting to be held December 10-13, 2022 in New Orleans, LA (Press release, Sana Biotechnology, NOV 3, 2022, View Source [SID1234622930]).

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"The presentations at ASH (Free ASH Whitepaper) will showcase the potential for both our allogeneic CAR T cell and in vivo delivery platforms to develop differentiated drugs for patients with hematologic malignancies," said Terry Fry, Sana’s Senior Vice President and Head of T Cell Therapeutics. "We are initially developing therapeutics for patients with lymphoma, leukemia, and multiple myeloma, and we look forward to presenting data on CD19-, CD22- and BCMA-targeted therapeutic candidates at the meeting."

Full abstracts are available for online viewing via the ASH (Free ASH Whitepaper) Annual Meeting website at www.hematology.org/meetings/annual-meeting. In addition, abstracts will be published online in the November supplemental issue of Blood, the journal of the American Society of Hematology (ASH) (Free ASH Whitepaper).

On November 3, 2022 2seventy bio, Inc. (Nasdaq: TSVT) reported that data from two cohorts of the KarMMa-2 study of Abecma (idecabtagene vicleucel) in patients who have suboptimal response to transplant or early relapse will be presented at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place from December 10-13, 2022, in New Orleans (Press release, 2seventy bio, NOV 3, 2022, View Source [SID1234622929]).

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"The growing body of data supporting Abecma has given us critical insight into which patients may benefit most from CAR T," said Steve Bernstein, M.D., chief medical officer, 2seventy bio. "While autologous stem cell transplant (ASCT) remains the standard of care, there is a high unmet medical need for patients with newly diagnosed and second-line, clinically high-risk multiple myeloma. We are seeing strong outcomes in patients who have suboptimal response to transplant (cohort 2c) and patients with an early relapse from transplant (cohort 2a) underscoring the importance of optimizing treatment for these patients. We plan to further evaluate this hypothesis in our registrational KarMMa-9 study in patients with newly diagnosed multiple myeloma who have a suboptimal response to transplant – a meaningful proportion of multiple myeloma patients."

New data from KarMMa-2, cohort 2a, a study performed in partnership with Bristol Myers Squibb (BMS), evaluating the efficacy and safety of Abecma in clinical high-risk multiple myeloma patients with early relapse after frontline ASCT, has been accepted as an oral presentation. Results suggest the clinical benefit of Abecma in high-risk patients who relapse early after transplant.

Data from KarMMa-2, cohort 2a, showed an overall response rate (ORR) of 83.8% (n=31) and a complete response rate (CRR) of 45.9%. The 12-month and 24-month progression-free survival (PFS) rates were 47.9% and 26.2%, respectively.

A poster presentation of KarMMa-2, cohort 2c, also in partnership with BMS, evaluating efficacy and safety of Abecma in patients with clinical high-risk multiple myeloma due to inadequate response (

Data from KarMMa-2, cohort 2c, showed an ORR of 87.1% (n=31) and a CRR of 74.2%. The 12-month and 24-month PFS rates were 90.1% and 83.1%, respectively. Data showed a 12-month and 24-month event-free overall survival (OS) rate of 100% among all treated patients. Despite low tumor burden, robust expansion was seen across patients treated.

Data suggest that Abecma can provide significant clinical benefit to patients with suboptimal response to transplant and support further evaluation of Abecma in newly diagnosed patients in our KarMMa-9 study described below.

Lower incidence and severity of cytokine release syndrome (CRS) and neurotoxicity (NT) were seen in newly diagnosed multiple myeloma patients versus those treated with Abecma in later lines. Safety data in both cohorts reinforce the known Abecma tolerability and favorable safety profile.

Abecma Development in Newly Diagnosed Patients

2seventy bio recently announced plans to initiate the KarMMa-9 study, in partnership with BMS, to evaluate Abecma (idecabtagene vicleucel) in newly diagnosed multiple myeloma patients who have suboptimal response to transplant, which represents a patient population with an unfavorable outcome. Of the approximately 70% newly diagnosed multiple myeloma patients who are eligible and chose to receive transplant, up to 50% do not achieve complete response post-transplant, underscoring the high unmet need in this population.

The company, in partnership with BMS, plans to provide additional information about the design and timing of the KarMMa-9 study at the earliest upcoming opportunity.

ASH Presentation Details
Oral Presentation [#361]: KarMMa-2 Cohort 2a: Efficacy and Safety of Idecabtagene Vicleucel in Clinical High-Risk Multiple Myeloma Patients with Early Relapse after Frontline Autologous Stem Cell Transplantation
Presenting Author: Saad Z. Usmani, MD, MBA, FACP, Hematologic Oncologist, Memorial Sloan Kettering Cancer Center, New York, N.Y.
Date/Time: Saturday, December 10, 2022, 4:00 p.m. ET

Poster Presentation [#3314]: KarMMa-2 Cohort 2c: Efficacy and Safety of Idecabtagene Vicleucel in Patients with Clinical High-Risk Multiple Myeloma Due to Inadequate Response to Frontline Autologous Stem Cell Transplantation
Presenting Author: Madhav V. Dhodapkar, MBBS, Director, Center for Cancer Immunology, Winship Cancer Institute of Emory University, Atlanta, Ga.
Date/Time: Sunday, December 11, 2022, 6:00 p.m. ET

About Abecma

Abecma is the first-in-class B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy approved in the U.S. for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Abecma recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

Abecma was approved by the U.S. Food and Drug Administration (FDA) in March 2021 for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Please see the Important Safety Information section below, including Boxed WARNINGS for Abecma regarding cytokine release syndrome, neurologic toxicities, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome and Prolonged Cytopenia. Abecma is being jointly developed and commercialized in the U.S. as part of a Co-Development, Co-Promotion, and Profit Share Agreement between Bristol Myers Squibb and 2seventy bio.

The companies’ broad clinical development program for Abecma includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-7, KarMMa-9) in earlier lines of treatment for patients with multiple myeloma. For more information visit clinicaltrials.gov.

Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, AND PROLONGED CYTOPENIA

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ABECMA. Do not administer ABECMA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic Toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ABECMA. Provide supportive care and/or corticosteroids as needed.
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) including fatal and life-threatening reactions, occurred in patients following treatment with ABECMA. HLH/MAS can occur with CRS or neurologic toxicities.
Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA.
ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS.
Cytokine Release Syndrome (CRS): CRS, including fatal or life-threatening reactions, occurred following treatment with ABECMA. CRS occurred in 85% (108/127) of patients receiving ABECMA. Grade 3 or higher CRS (Lee grading system) occurred in 9% (12/127) of patients, with Grade 5 CRS reported in one (0.8%) patient. The median time to onset of CRS, any grade, was 1 day (range: 1 – 23 days) and the median duration of CRS was 7 days (range: 1 – 63 days) in all patients including the patient who died. The most common manifestations of CRS included pyrexia (98%), hypotension (41%), tachycardia (35%), chills (31%), hypoxia (20%), fatigue (12%), and headache (10%). Grade 3 or higher events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, acute respiratory distress syndrome (ARDS), atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, multiple organ dysfunction syndrome and HLH/MAS.

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

Fifty four percent (68/127) of patients received tocilizumab; 35% (45/127) received a single dose while 18% (23/127) received more than 1 dose of tocilizumab. Overall, across the dose levels, 15% (19/127) of patients received at least 1 dose of corticosteroids for treatment of CRS. All patients that received corticosteroids for CRS received tocilizumab.

Overall rate of CRS was 79% and rate of Grade 2 CRS was 23% in patients treated in the 300 x 106 CAR+ T cell dose cohort. For patients treated in the 450 x 106 CAR+ T cell dose cohort, the overall rate of CRS was 96% and rate of Grade 2 CRS was 40%. Rate of Grade 3 or higher CRS was similar across the dose range. The median duration of CRS for the 450 x 106 CAR+ T cell dose cohort was 7 days (range: 1-63 days) and for the 300 x 106 CAR+ T cell dose cohort was 6 days (range: 2-28 days). In the 450 x 106 CAR+ T cell dose cohort, 68% (36/53) of patients received tocilizumab and 23% (12/53) received at least 1 dose of corticosteroids for treatment of CRS. In the 300 x 106 CAR+ T cell dose cohort, 44% (31/70) of patients received tocilizumab and 10% (7/70) received corticosteroids. All patients that received corticosteroids for CRS also received tocilizumab. Ensure that a minimum of 2 doses of tocilizumab are available prior to infusion of ABECMA.

Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated.

Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Neurologic Toxicities: Neurologic toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. CAR T cell-associated neurotoxicity occurred in 28% (36/127) of patients receiving ABECMA, including Grade 3 in 4% (5/127) of patients. One patient had ongoing Grade 2 neurotoxicity at the time of death. Two patients had ongoing Grade 1 tremor at the time of data cutoff. The median time to onset of neurotoxicity was 2 days (range: 1 – 42 days). CAR T cell-associated neurotoxicity resolved in 92% (33/36) of patients with a median duration of neurotoxicity was 5 days (range: 1 – 61 days). The median duration of neurotoxicity was 6 days (range: 1 – 578) in all patients including those with ongoing neurotoxicity at the time of death or data cut off. Thirty-four patients with neurotoxicity had CRS. Neurotoxicity had onset in 3 patients before, 29 patients during, and 2 patients after CRS. The rate of Grade 3 neurotoxicity was 8% in the 450 x 106 CAR+ T cell dose cohort and 1.4% in the 300 x 106 CAR+ T cell dose cohort. The most frequently reported (greater than or equal to 5%) manifestations of CAR T cell-associated neurotoxicity include encephalopathy (20%), tremor (9%), aphasia (7%), and delirium (6%). Grade 4 neurotoxicity and cerebral edema in 1 patient has been reported with ABECMA in another study in multiple myeloma. Grade 3 myelitis and Grade 3 parkinsonism have been reported after treatment with ABECMA in another study in multiple myeloma.

Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs and symptoms of neurologic toxicities. Rule out other causes of neurologic symptoms. Monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.

Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): HLH/MAS occurred in 4% (5/127) of patients receiving ABECMA. One patient treated in the 300 x 106 CAR+ T cell dose cohort developed fatal multi-organ HLH/MAS with CRS. In another patient with fatal bronchopulmonary aspergillosis, HLH/MAS was contributory to the fatal outcome. Three cases of Grade 2 HLH/MAS resolved. The rate of HLH/MAS was 8% in the 450 x 106 CAR+ T cell dose cohort and 1% in the 300 x 106 CAR+ T cell dose cohort. All events of HLH/MAS had onset within 10 days of receiving ABECMA with a median onset of 7 days (range: 4-9 days) and occurred in the setting of ongoing or worsening CRS. Two patients with HLH/MAS had overlapping neurotoxicity. The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, and cytopenia. HLH/MAS is a potentially life-threatening condition with a high mortality rate if not recognized early and treated. Treatment of HLH/MAS should be administered per institutional standards.

ABECMA REMS: Due to the risk of CRS and neurologic toxicities, ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS. Further information is available at www.AbecmaREMS.com or 1-888-423-5436.

Hypersensitivity Reactions: Allergic reactions may occur with the infusion of ABECMA. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in ABECMA.

Infections: ABECMA should not be administered to patients with active infections or inflammatory disorders. Severe, life-threatening, or fatal infections occurred in patients after ABECMA infusion. Infections (all grades) occurred in 70% of patients. Grade 3 or 4 infections occurred in 23% of patients. Overall, 4 patients had Grade 5 infections (3%); 2 patients (1.6%) had Grade 5 events of pneumonia, 1 patient (0.8%) had Grade 5 bronchopulmonary aspergillosis, and 1 patient (0.8%) had cytomegalovirus (CMV) pneumonia associated with Pneumocystis jirovecii. Monitor patients for signs and symptoms of infection before and after ABECMA infusion and treat appropriately. Administer prophylactic, preemptive, and/or therapeutic antimicrobials according to standard institutional guidelines.

Febrile neutropenia was observed in 16% (20/127) of patients after ABECMA infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

Viral Reactivation: Cytomegalovirus (CMV) infection resulting in pneumonia and death has occurred following ABECMA administration. Monitor and treat for CMV reactivation in accordance with clinical guidelines. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against plasma cells. Perform screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias: Patients may exhibit prolonged cytopenias following lymphodepleting chemotherapy and ABECMA infusion. In the KarMMa study, 41% of patients (52/127) experienced prolonged Grade 3 or 4 neutropenia and 49% (62/127) experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following ABECMA infusion. Rate of prolonged neutropenia was 49% in the 450 x 106 CAR+ T cell dose cohort and 34% in the 300 x 106 CAR+ T cell dose cohort. In 83% (43/52) of patients who recovered from Grade 3 or 4 neutropenia after Month 1, the median time to recovery from ABECMA infusion was 1.9 months. In 65% (40/62) of patients who recovered from Grade 3 or 4 thrombocytopenia, the median time to recovery was 2.1 months. Median time to cytopenia recovery was similar across the 300 and 450 x 106 dose cohort.

Three patients underwent stem cell therapy for hematopoietic reconstitution due to prolonged cytopenia. Two of the three patients died from complications of prolonged cytopenia. Monitor blood counts prior to and after ABECMA infusion. Manage cytopenia with myeloid growth factor and blood product transfusion support according to institutional guidelines.

Hypogammaglobulinemia: Plasma cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with ABECMA. Hypogammaglobulinemia was reported as an adverse event in 21% (27/127) of patients; laboratory IgG levels fell below 500 mg/dl after infusion in 25% (32/127) of patients treated with ABECMA.

Monitor immunoglobulin levels after treatment with ABECMA and administer IVIG for IgG <400 mg/dl. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

The safety of immunization with live viral vaccines during or following ABECMA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during ABECMA treatment, and until immune recovery following treatment with ABECMA.

Secondary Malignancies: Patients treated with ABECMA may develop secondary malignancies. Monitor life-long for secondary malignancies. If a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 to obtain instructions on patient samples to collect for testing of secondary malignancy of T cell origin.

Effects on Ability to Drive and Operate Machinery: Due to the potential for neurologic events, including altered mental status or seizures, patients receiving ABECMA are at risk for altered or decreased consciousness or coordination in the 8 weeks following ABECMA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions: The most common nonlaboratory adverse reactions (incidence greater than or equal to 20%) include CRS, infections – pathogen unspecified, fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite.

On November 3, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported that it will present a poster on CTX110, its wholly-owned allogeneic CAR-T cell investigational therapy targeting CD19+ B-cell malignancies, at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2022 Annual Meeting, taking place December 10-13, 2022, virtually and at the Ernest N. Morial Convention Center in New Orleans, Louisiana (Press release, CRISPR Therapeutics, NOV 3, 2022, View Source [SID1234622928]).

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The ASH (Free ASH Whitepaper) abstract includes preliminary data from 32 patients with Large B-Cell Lymphoma (LBCL) who have been dosed in the Company’s ongoing Phase 1 CARBON trial evaluating the safety and efficacy of CTX110. The poster presentation will include updated results from the CARBON trial.

The ASH (Free ASH Whitepaper) abstract is now available at www.hematology.org.

Title: CTX110 Allogeneic CRISPR-Cas9–Engineered CAR-T Cells in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): Results From the Phase 1 Dose Escalation CARBON Study
Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster III
Session Date: Monday, December 12, 2022
Presentation Time: 6:00 PM – 8:00 PM ET
Abstract Number: 4629
Location: Ernest N. Morial Convention Center, Hall D

About CTX110 and CARBON Trial
CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting cluster of differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON trial, a Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies. CTX110 has been granted Regenerative Medicine Advanced Therapy designation from the FDA.