Emerging immunotherapies in multiple myeloma – The BMJ
By daniellenierenberg
Immunotherapies that are currently being studied in multiple myeloma are discussed in this section under four headings: checkpoint inhibitors, chimeric antigen receptor (CAR) T cells, bispecific antibodies, and antibody drug conjugates (fig 2).
Malignant plasma cells in most patients with multiple myeloma express the checkpoint programmed death-ligand 1, which is upregulated especially when exposed to inflammatory mediators such as interferon . Interaction of this checkpoint molecule with programmed cell death protein 1 on T cells limits their proliferation and cytotoxic activity.6869
The first study evaluating single agent nivolumab for relapsed multiple myeloma showed a response in only one of 27 patients.7071 Despite a lack of single agent activity, single arm trials combining checkpoint inhibitors with immunomodulatory imide drugs and dexamethasone because of the potential synergy72 look promising.7374
With these clinical data, three large randomized phase III trials were halted by the FDA in 2017 because of increased serious adverse events and deaths as well as decreased overall survival in the checkpoint inhibitor arm (pomalidomide and dexamethasone with and without pembrolizumab) in relapsed and refractory multiple myeloma (hazard ratio 1.61, 95% confidence interval 0.91 to 2.85),75 pomalidomide and dexamethasone with and without nivolumab in relapsed and refractory multiple myeloma (1.19, 0.64 to 2.20),76 and lenalidomide and dexamethasone with and without pembrolizumab in transplant ineligible patients with newly diagnosed multiple myeloma (2.06, 0.93 to 4.55)77).
These trials encourage caution with expedited timelines for future combination studies for drugs with limited single agent activity.7879 Future trials in multiple myeloma will need to be based on sound preclinical and clinical rationale with other partners and be conducted in heavily treated patients (with limited standard options) initially.
CAR T cells are human T cells that have been genetically modified and expanded in the laboratory before they are infused back into patients to target the tumor. The receptor on the surface of CAR T cells that targets the tumor antigens consists of several parts (fig 3): an extracellular, non-major histocompatibility complex restricted, targeting domain, usually derived from a single chain variable fragment of a monoclonal antibody; a spacer region; a transmembrane domain; an intracellular signaling domain including the CD3 activation domain; and a costimulatory domain (eg, CD28 or 4-1BB). The single chain variable fragment was originally derived from mice (hence the term chimeric), but many of the newer constructs are fully human.8081
Chimeric antigen receptor (CAR) T cell structure
CD3 positive T cells are obtained from patients (for autologous CAR T cells) or healthy donors (for allogeneic CAR T cells) via a process called leukapheresis. These T cells are expanded manifold in culture and activated using beads coated with anti-CD3 or anti-CD28 monoclonal antibodies or cell based artificial antigen presenting cells.82 The T cells are then transduced with a vector (usually either lentiviral or retroviral) that carries the gene encoding a receptor to an antigen present on the surface of tumor cells. This manufacturing process takes up to four weeks at a good manufacturing practices facility, and the CAR T cells can then be stored until needed by the patient. This delay means that the disease must not be rapidly progressing, so that the patient is able to wait until the CAR T product is ready; otherwise the patient will need bridging chemotherapy. Two to seven days before CAR T cell infusion, a patient receives lymphodepleting chemotherapy to make way for the CAR T cells that are subsequently given as an intravenous infusion. Once infused into patients, the CAR T cells encounter the antigen, proliferate, and kill the tumor cells (fig 4). These cells, therefore, combine the target specificity of a monoclonal antibody with the enhanced cytotoxicity of T cells without requiring human leucocyte antigen presentation of the target antigen.83
Chimeric antigen receptor (CAR) T cell treatment for multiple myelomasequence of events. CRS=cytokine release syndrome; ICANS=immune effector cell associated neurotoxicity syndrome
An ideal antigen is one that is widely and exclusively expressed on cancer cells but not on normal cells to enhance efficacy and reduce toxicity.8485 In multiple myeloma, most emerging immunotherapies (including CAR T cells) target B cell maturation antigen (BCMA), a type III transmembrane receptor, which is a promising target antigen.8687 BCMA is also known as tumor necrosis factor receptor superfamily member 17 or CD269. It is expressed in nearly all plasma cells (normal and malignant) although its expression is variable.88 BCMA promotes plasma cell survival and is induced during plasma cell differentiation89 by binding to ligands (a proliferation inducing ligand (APRIL) and B cell activating factor (BAFF)) that are produced by osteoclasts.90 Increased levels of soluble BCMA are associated with high tumor burden in multiple myeloma and thus worse outcomes.91
CAR T cells targeting CD19 were approved by the FDA in 2017 for refractory large B cell lymphoma9293 and acute lymphoblastic leukemia,94 and are being used in clinical practice. The first study on CAR T cell treatment directed by BCMA opened in 2014 at the US National Cancer Institute.879596 Since then, about a dozen of different early phase clinical trials have been conducted on BCMA CAR T treatment for advanced multiple myeloma.9798 A detailed review outlining the differences in the construct, manufacturing, and clinical efficacy of these different products has been published previously.8186
This review focuses on four BCMA CAR T cell products that are currently being evaluated in registration (that is, for regulatory approval) phase I/II clinical trials for patients with relapsed and refractory multiple myeloma. These products include bb2121 (now known as idecabtagene vicleucel or ide-cel), JCARH125 (now known as orvacabtagene autoleucel or orva-cel), LCAR-B38M (now known as JNJ-4528), and P-Bcma-101. FDA approvals for some of these agents are anticipated in 2020-21 for relapsed and refractory multiple myeloma (fig 5; table 2). The high overall response rates of 60-100% seen in these trials in a highly refractory population is unprecedented, although the durability of these responses is still in question.
Four major constructs of chimeric antigen receptor (CAR) T cells targeting B cell maturation antigens (BCMA), currently in multicenter clinical trials investigating multiple myeloma. This figure does not include all BCMA constructs in multiple myeloma. ScFv=single chain variable fragment; VH only=variable-heavy chain only fragments
Summary of major multicenter clinical trials investigating multiple myeloma treatments*
The most advanced CAR T cell treatment targeting a BCMA is ide-cel (bb2121), which uses a lentiviral vector for CAR insertion and includes a 4-1BB costimulatory domain as well as a murine single chain variable fragment.114 In a phase I non-randomized, open label, multicenter trial in relapsed and refractory multiple myeloma (3 prior lines of treatment) for 33 patients treated at various doses,115 researchers found an overall response rate of 85% with a median progression free survival of 11.8 months. A higher overall response rate was seen at the higher dose levels and doses of 150-450106 CAR T cells were defined as the active dose.115 This dose is being tested currently in a multicenter, single arm, open label trial to evaluate bb2121 CAR T cells further in relapsed and refractory multiple myeloma; the trial has completed enrolment of 149 patients worldwide. Preliminary results show an overall response rate of 73% (complete response rate 33%) and median progression free survival of 8.8 months in 128 patients treated at doses of 150-450106 cells (table 2).99 Fifty four patients treated at the highest dose level of 450106 cells had an overall response rate of 82% and a median progression free survival of 12.1 months.99 These results have been submitted to regulatory agencies including the FDA and European Medicines Agency for treatment for advanced multiple myeloma.
Orva-cel (JCARH125) is another second generation CAR product with a fully human B cell derived single chain variable fragment, a 4-1BB costimulatory domain, and optimized manufacturing (predefined CD4:CD8 ratio) that is derived from preclinical work at Memorial Sloan Kettering Cancer Center. The preliminary data for the multicenter phase I/II EVOLVE study were presented at the American Society of Clinical Oncology meeting in 2020. These patients had received a median of six prior treatments. They received escalating doses of 50-600106 cells. The results for 62 patients treated at the 300-600106 cells dose range showed an overall response rate of 92% (complete response rate 36%).100101 The trial is currently enrolling at the recommended phase II dose of 600106 cells (table 2).
The LCAR-B38M CAR construct was developed initially in China and is currently being pursued in the US and globally as JNJ-4528 (table 2). It consists of two llama derived variable-heavy chain only fragments that target two epitopes of BCMA designed to confer avidity. In a phase I/II study in China, researchers found deep durable responses with a median progression free survival of 19.9 months and a manageable safety profile in relapsed and refractory multiple myeloma, although the patients in this study were treated earlier in their disease course with a median of three prior lines of treatment and were therefore less heavily pre-treated.102103104105 In the US and Europe, a multicenter phase Ib/II clinical trial of this CAR construct as JNJ-4528 in relapsed and refractory multiple myeloma (3 prior lines of treatment) was conducted to confirm the findings of the LEGEND-2 study. Preliminary results of the phase Ib portion showed an overall response rate of 100% (complete response rate 86%) in patients with a median of five prior lines of treatment (table 2).106107 The phase II portion is fully enrolled, and phase II and III studies have been initiated.
P-BCMA-101 is uniquely manufactured using the non-viral piggyBac gene editing system, which is less costly, produces cells with a high percentage of favorable stem cell memory phenotype T cells, and has the ability to include a safety switch. The binding molecule for this product is not a single chain variable fragment but a small fully human fibronectin domain (Centyrin) that has higher specificity and potentially less immunogenicity. In a phase I dose escalation trial, the overall response rate was 63% with a median progression free survival of 9.5 months in 19 evaluable patients108 (table 2).
CAR T cell treatments have a unique toxicity profile where patients can develop side effects such as cytokine release syndrome and neurotoxicity that has been recently termed immune effector cell associated neurotoxicity syndrome (ICANS).116 Cytokine release syndrome has been defined as a disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, or hypoxia caused by the release of cytokines from cells. The American Society for Transplantation and Cellular Therapy has developed a consensus grading system for cytokine release syndrome, which depends on the severity and presence of fever, hypotension, or hypoxia (table 3).116
American Society for Transplantation and Cellular Therapy consensus grading for cytokine release syndrome (CRS)116
ICANS has been defined as a disorder involving the central nervous system following any immunotherapy that results in the activation or engagement of endogenous or infused T cells or other immune effector cells. Symptoms or signs can be progressive and could include aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral edema.116 It includes four grades that are determined by the ICE score (immune effector cell associated encephalopathy score, which provides objectivity to grading encephalopathy), level of consciousness, seizure, motor findings, and elevated intracranial pressure or cerebral edema (table 4).116 Management of ICANS and cytokine release syndrome is based on grading and involves supportive care, steroids, and interleukin blocking agents.117118 Interleukin 6 blocking agents (tocilizumab and siltuximab) with or without steroids are the mainstay of management for cytokine release syndrome, whereas steroids are the mainstay for the management of neurotoxicity. Another potential agent for managing these symptoms includes the interleukin 1 blocking agent anakinra.119
American Society for Transplantation and Cellular Therapy consensus grading for immune effector cell associated neurotoxicity syndrome (ICANS) in adults116
All the clinical trials on BCMA CAR T cell treatments had a high incidence of cytokine release syndrome (>80%) except for P-BCMA-101, which seemed to have a substantially lower incidence (10%). Despite this, severe cytokine release syndrome (that is, grade 3) is seen in less than 10% of patients. Neurotoxicity was reported in less than 20% of patients with severe neurotoxicity (grade 3) in less than 7% of patients. Another common side effect is cytopenia, which has also been thought to be secondary to the lymphodepleting chemotherapy, ongoing CAR T cell activity, and disruption of hematopoiesis showing severe hypocellularity in the bone marrow, but most patients recover with time.120121
Early recognition of cytokine release syndrome and ICANS and prompt intervention after CAR T cell treatment is vital to prevent serious consequences, although the optimal timing for intervention and benefit of prophylactic treatment is yet unknown.122 The CAR T cell therapy associated toxicity (CARTOX) working group has developed a management approach for these syndromes, based on multidisciplinary grades.123 In cytokine release syndrome, patients with grade 1 are usually managed with supportive care, those with grade 2 are managed with the anti-interleukin 6 receptor tocilizumab with or without steroids in addition to supportive care, and those with grade 3-4 are managed in the intensive care unit with aggressive supportive care, vasopressors, oxygen, tocilizumab, and steroids. Patients with grade 1 and 2 ICANS are managed supportively but an electroencephalogram is done to rule out electrical seizures and imaging of the brain to rule out edema. Patients with grade 3 and 4 ICANS need steroids and more aggressive supportive care.120
Bispecific monoclonal antibodies direct a hosts immune system (more specifically cytotoxic T cells) against cancer cells by binding CD3 on T cells with a target protein on cancer cells (fig 6).124 A type of bispecific antibody is the bispecific T cell engager (BiTE), which differs from other bispecific antibodies by containing two different single chain variable fragments connected by a linker. BiTEs often have a short half life, requiring continuous infusion to maintain efficacy.125 The first BiTE to receive FDA approval for treatment in relapsed and refractory acute lymphoblastic leukemia is Blinatumomab, a bispecific antibody that engages T cells to CD19 positive cells.126 Because BiTEs engage and activate the patients own immune cells, they have a toxicity profile similar to CAR T cells including cytokine release syndrome and ICANS.116
Structure of a bispecific antibody. BiTEs=bispecific T cell engagers
AMG 420 (previously named BI 836909) is a novel BiTE targeting BCMA on myeloma cells and CD3 on T cells, which has induced multiple myeloma cell lysis in preclinical models.127 In the first-in-human phase I study of AMG 420 in patients with at least two lines of treatment, AMG 420 was given as a continuous infusion with a pump for four week infusions, six week cycles, and a maximum of 10 cycles. The maximum tolerated dose was 400 g/day; seven (70%) of 10 patients responded to this dose. Serious adverse events were seen in 48% of patients, which were most commonly infections; and two patients had reversible grade 3 polyneuropathies. Cytokine release syndrome developed in 38% of patients, with no toxicity in the central nervous system.109 A phase Ib trial with AMG 420 is currently ongoing and although this drug looks promising, the continuous intravenous infusions present logistical challenges for patients and healthcare systems (table 2). AMG 701 is a modified version of AMG 420 (by addition of an Fc domain) with an extended half life that is suitable for dosing once a week and is being investigated in a phase I study.128
Another BCMA bispecific antibody, CC-93269, is being studied in an ongoing phase I clinical trial. This humanized 2+1, immunoglobulin G 1 based, T cell engager binds to BCMA bivalently on myeloma cells and CD3 monovalently on T cells. The bivalent binding could lead to improved potency, tumor targeting, and retention.129 All doses (range 0.15-10 mg) were given intravenously over two hours weekly for the first three cycles, every two weeks for the next three cycles, and then monthly. The most common treatment emergent adverse events of grade 3 or higher included neutropenia, anemia, and infections. Cytokine release syndrome was seen in 77% of patients, with all events developing after the first dose and less common with subsequent doses. The incidence increased with higher doses, and only one patient had cytokine release syndrome of grade 3 or higher leading to their death. In 30 patients treated, the overall response rate was 43.3% and dose dependent. The overall response rate was 88.9% in nine patients in the highest dose cohort.110
Teclistamab (JNJ-64007957) is a humanized, immunoglobulin G-4 based, bispecific DuoBody antibody that binds to BCMA and CD3 that is being studied in a phase I clinical trial. In the dose escalation part, 78 patients received doses ranging from 0.3 g/kg to 720 g/kg. The drug is given intravenously every week, with one to three step-up doses given within one week before the full dose. The overall response rate was dose dependent with no responses at doses 0.3-19.2 g/kg, 30% at 38.4-180 g/kg, and 67% at 270 g/kg. Cytokine release syndrome was seen in 56% of patients overall and 65% patients at doses over 38.4 g/kg. The most common adverse events at grade 3 or higher that were related to treatment were cytopenias and infections (table 2).111
Antibody drug conjugates are complex molecules composed of an antibody that targets cancer cells and are linked to a biologically active cytotoxic drug (known as the payload; fig 7).125 Belantamab mafodotin (GSK2857916) is a novel humanized and afucosylated (to improve antibody dependent cell mediated cytotoxicity) antibody drug conjugate that targets BCMA. It consists of an anti-BCMA monoclonal antibody conjugated to monomethyl auristatin F, a potent microtubule inhibitor.130 This antibody drug conjugate was shown to have selective myeloma cell killing in vitro and in vivo thus setting the stage for clinical trials.130131
Structure of an antibody drug conjugate
This antibody was studied in a two part phase I study. The drug was well tolerated with no dose limiting toxicities, although corneal events (such as blurry vision, dry eyes, photophobia) were seen in about 58% of patients; these events are a known toxicity of monomethyl auristatin F.132 In the dose expansion phase, 35 patients were treated, and the overall response rate was 60% with a median progression free survival 12 months.133 In a phase II, two arm study, the antibody was used in patients with relapsed and refractory multiple myeloma who had failed at least three lines of treatment. The overall response rate was 31% at the 2.5 mg/kg dose and 34% at the 3.3 mg/kg dose, which was significantly lower than the phase I study. The corneal changes or keratopathy were seen in 70% and 75% of patients, respectively. Owing to the similar response rates with the 2.5 mg/kg and 3.3 mg/kg doses and a more favorable side effect profile with the lower dose, 2.5 mg/kg will be the dose used for future studies.112 Based on these data, belantamab is the first anti-BCMA treatment to be FDA approved for relapsed and refractory multiple myeloma patients who have received four prior treatments including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.
Preliminary results for another study with 18 patients treated on the belantamab, bortezomib, and dexamethasone arm was presented recently, with an overall response rate of 78%; however, all 18 patients developed grade 1-3 keratopathy.113 This visual toxicity is a unique but potentially serious side effect to this drug that needs close monitoring with an ophthalmologist. Another antibody drug conjugate, DFRF4539A, is an anti-FcRH5 (also known as FcRL5) antibody conjugated to monomethyl auristatin and has shown limited activity and high incidence of toxicity in a phase I study; therefore, it was unsuccessful for this disease (table 2).134135
Read more here:
Emerging immunotherapies in multiple myeloma - The BMJ
- Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune ... - Nature.com - April 28th, 2024
- Stem Cell Therapy: Know How The Procedure Stops Cancer - Times Now - April 28th, 2024
- Rejuvenating the immune system by depleting certain stem cells - National Institutes of Health (NIH) (.gov) - April 19th, 2024
- New gene therapy eliminates need for bone marrow transplant. Here's how it works. - CBS News - April 19th, 2024
- New gene therapy eliminates need for bone marrow transplant. Here's how it works. - MSN - April 19th, 2024
- Long Island boy with rare blood disorder undergoes gene therapy - MSN - April 19th, 2024
- Philadelphia Wings player, Connecticut man will be forever bonded by bone marrow donation: "He's my hero" - CBS Philly - April 10th, 2024
- VRD versus VCD as induction therapy before autologous stem cell transplantation in multiple myeloma: a nationwide ... - Nature.com - April 10th, 2024
- Register as a bone marrow donor today and save lives - The Citizen - April 10th, 2024
- Resilient anatomy and local plasticity of naive and stress haematopoiesis - Nature.com - March 26th, 2024
- A Deeper Depth of Response After Salvage Therapy Improves Outcomes of Autologous Stem Cell Transplantation in ... - Cureus - March 26th, 2024
- Iron restriction keeps blood stem cells young, researchers find - Phys.org - March 18th, 2024
- Blood drive, bone marrow testing to be held in local woman's memory - The Winchester Star - March 18th, 2024
- Signal of Benefit for Stem Cell Therapy in Progressive MS - Medscape - March 10th, 2024
- Woman, 22, With Leukemia Recalls Symptoms And New Treatment She Received: EXCLUSIVE - TODAY - March 10th, 2024
- This Swedish startup wants to reduce the cost, and controversy, around stem cell production - TechCrunch - March 10th, 2024
- Outcomes and prognosis of haploidentical haematopoietic stem cell transplantation in children with FLT3-ITD mutated ... - Nature.com - March 10th, 2024
- Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor ... - Nature.com - March 10th, 2024
- Hematopoietic cell transplantation and cell therapy activity landscape survey in the Kingdom of Saudi Arabia; a report ... - Nature.com - March 10th, 2024
- How an MS friendship led to HSCT and a love of running - Multiple Sclerosis News Today - March 10th, 2024
- Iron Limitation Preserves Youthfulness of Blood Stem Cells - Mirage News - March 10th, 2024
- Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis: A retrospective analysis of the ... - Nature.com - March 10th, 2024
- AJMC in the Press, February 23, 2024 - AJMC.com Managed Markets Network - February 24th, 2024
- Orca Bio Presents Promising Data on Orca-T in Two Oral Presentations at the 2024 Tandem Meetings of ASTCT and ... - Yahoo Finance - February 24th, 2024
- New approaches to live-track the production of different types of blood cells in mice - Medical Xpress - February 24th, 2024
- If Other Treatments Aren't Working -- Stem Cell Transplant May Be A Good Option In CLL - SurvivorNet - February 24th, 2024
- Expanding the Horizons of Cell and Gene Therapy - RegMedNet - February 24th, 2024
- The strangers who saved each others lives - BBC - February 24th, 2024
- City of Hope Research Featuring the Successful Treatment of the Oldest Patient to Achieve Remission for Leukemia ... - StreetInsider.com - February 15th, 2024
- 3D printing and material processing combined to create artificial bone - Optics.org - February 15th, 2024
- Man, 63, is in remission from HIV five years after receiving groundbreaking stem cell transplant... - The Sun - February 15th, 2024
- Team demonstrates fabrication method to construct 3D structures that mimic bone microstructure - Phys.org - February 15th, 2024
- Hematopoietic Stem Cells and Their Role in Development and Disease Therapy - The Scientist - February 15th, 2024
- Blood cell family trees trace how production changes with aging - MIT News - February 7th, 2024
- New study on promising stem cell-based therapy for Crohn's disease - Medical Xpress - January 30th, 2024
- Second haploidentical bone marrow transplantation with antithymocyte antibody-containing conditioning regimen for ... - Nature.com - January 30th, 2024
- Stem cell study shows how gene activity modulates the amount of immune cell production in mice - Medical Xpress - January 30th, 2024
- Global Stem Cell Therapy Industry Outlook to 2028, Driven by Therapeutic Innovations and Clinical Advancements ... - Yahoo Finance - January 30th, 2024
- 1st-of-its-kind therapy blocks immune attack after stem-cell transplant - Livescience.com - January 22nd, 2024
- Individualized dose of anti-thymocyte globulin based on weight and pre-transplantation lymphocyte counts in pediatric ... - Nature.com - January 22nd, 2024
- Implications of stress-induced gene expression for hematopoietic stem cell aging studies - Nature.com - January 22nd, 2024
- LVHN announces opening of new stem cell transplant center. Here's what that means for the Lehigh Valley - The Morning Call - January 22nd, 2024
- Fast Five Quiz: Chronic GVHD Risk Factors and Prevention - Medscape Reference - January 22nd, 2024
- Could Treatments for HIV and Sickle Cell Open the Gene Therapy Floodgates? - BioSpace - January 22nd, 2024
- Effects of fine particulate matter on bone marrow-conserved hematopoietic and mesenchymal stem cells: a systematic ... - Nature.com - January 14th, 2024
- Donating Bone Marrow and Stem Cells: The Process and What To Expect - On Cancer - Memorial Sloan Kettering - January 14th, 2024
- No, Rep. Steve Scalise Didn't Vote Against Stem Cell Research From Which He Is Now Benefiting - Yahoo News - January 14th, 2024
- Hematopoietic Stem Cell Transplantation Market to Grow Rapidly During the Study Period (2019-2032), Evaluates ... - PR Newswire - January 14th, 2024
- Life-saving donation from Philly athlete saves life: 'Feeling so strong, I owe that all to him' - AOL - January 14th, 2024
- The Key to Creating Blood Stem Cells May Lie in Your Own Blood - ScienceAlert - January 14th, 2024
- Dr Phillips on the Rationale for the GLOBRYTE Trial in Relapsed/Refractory MCL - OncLive - January 14th, 2024
- COVID-19 and HSCT Recipients: Risk Factors and Prevention Measures - Medriva - January 14th, 2024
- Bone Marrow Transplant: Heres What You Need To Know About This Therapy - Times Now - January 5th, 2024
- New insights about the development of hematopoietic stem cells - Drug Target Review - December 28th, 2023
- Bone Marrow Transplantation | Johns Hopkins Medicine - December 20th, 2023
- Stem Cell or Bone Marrow Transplant | American Cancer Society - December 20th, 2023
- Embryonic-stem-cell-derived mesenchymal stem cells relieve experimental contact urticaria by regulating the functions ... - Nature.com - December 20th, 2023
- Researchers discover crucial step in creating blood stem cells - Phys.org - December 20th, 2023
- A niche topic: understanding the development of hematopoietic stem cells - Fred Hutchinson Cancer Center - December 20th, 2023
- Vertex developed a CRISPR cure. Its already on the hunt for something better. - MIT Technology Review - December 20th, 2023
- FDA approves cure for sickle cell disease, the first treatment to use gene-editing tool CRISPR - NBC News - December 12th, 2023
- First therapy using CRISPR technology will treat sickle cell disease - Morning Brew - December 12th, 2023
- 7 medical breakthroughs that gave us hope in 2023 - National Geographic - December 12th, 2023
- Understanding Chronic Myeloid Leukemia: Causes, Symptoms, and Treatment - Everyday Health - December 12th, 2023
- Mansour bin Zayed witnesses inauguration of ADSCC Bone Marrow Transplant & Cellular Therapy Congress 2023 - ZAWYA - November 26th, 2023
- ADSCC Bone Marrow Transplant and Cellular Therapy Congress 2023 to take place in Abu Dhabi - ZAWYA - November 18th, 2023
- Orchard Therapeutics Reports First Quarter 2023 Financial Results and Announces Initiation of Rolling Submission for Biologics License Application of... - May 16th, 2023
- Family of 7-month-old in need of bone marrow transplant hosting donor registration event - CBS Pittsburgh - May 8th, 2023
- Anika Continues to Expand Addressable Market for Tactoset Injectable Bone Substitute with Additional 510(k) Clearance from FDA - Marketscreener.com - April 5th, 2023
- MorphoSys Completes Enrollment of Phase 3 MANIFEST-2 Study of Pelabresib in Myelofibrosis with Topline Results Expected by End of 2023 -... - April 5th, 2023
- VOR BIOPHARMA INC. Management's Discussion and Analysis of Financial Condition and Results of Operations (form 10-K) - Marketscreener.com - March 25th, 2023
- BioRestorative Therapies to Seek FDA Approval to Expand the Clinical Application of BRTX-100 - Marketscreener.com - March 17th, 2023
- BioSenic delivers a new post-hoc analysis of its Phase III JTA-004 trial on knee osteo-arthritis with positive action on the most severely affected... - March 17th, 2023
- JASPER THERAPEUTICS, INC. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com - March 9th, 2023
- For a range of unmet medical needs, India offers a fantastic opportunity to push cell and gene therapies: B .. - ETHealthWorld - March 9th, 2023
- NGM BIOPHARMACEUTICALS INC Management's Discussion and Analysis of Financial Condition and Results of Operations. (form 10-K) - Marketscreener.com - March 1st, 2023
- Bone health: Tips to keep your bones healthy - Mayo Clinic - January 27th, 2023
- Bone marrow drive held for military wife with cancer - January 27th, 2023
- Bone cancer - Symptoms and causes - Mayo Clinic - January 27th, 2023
- Bone | Definition, Anatomy, & Composition | Britannica - January 19th, 2023