T-cell transfer therapy. Different technological approaches are evolving, such as bicistronic CAR T cells, tandem CAR T cells, and CAR T-cell products for 2 different targets administered together or sequentially. Biologically, the monoclonal antibody attaches to the myeloma cell, which is endocytosed into the cell. 59th American Society of Hematology Annual Meeting and Exposition. Finally, CAR-T cells are infused into the patients bloodstream to kill the tumor cells, Five generations of CAR-T cells. The engineered CAR T . [Historically], we would see, at most, a 20% likelihood of achieving a complete remission (CR). Neelapu SS, Locke FL, Bartlett NL, et al. Bispecific antibodies are a little bit further away from receiving regulatory approval, but are also BCMA-directed therapies. The authors declare that they have no competing interests. In addition to easier access, third-party cell donors might help to overcome the issues of lymphopenia and disease- and patient-related T-cell dysfunction that compromise the success of adoptively transferred autologous cell products. We're improving the lives of cancer patients and their families through advocacy, research, and patient support to ensure that everyone has an opportunity to prevent, detect, treat, and survive cancer. Even if we dont cure patients, we can make it a chronic disease, said Vesole. We are going to be individualizing precision medicine and treating patients specific DNA abnormalities in their myeloma cells. For patients who have multiple myeloma and adequate physiologic organ function, and agree to [undergo] transplant, transplant is considered standard. Currently, triplet therapy seems to be the standard of care, but what is evolving is whether we should give quadruplet regimens with monoclonal antibodies in addition to those same 3 classes of drugs I mentioned. Thalidomide can also cause drowsiness, fatigue, and severe constipation. To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects. The Case for CAR Martin explained that CAR T-cell therapy is human T lymphocytes in which a gene has been inserted, typically using a retrovirus or adenovirus, and the gene has an extracellular domain that binds to the cell of interest, a transmembrane domain, and an intracellular signaling domain. Keywords: Grade 3 CRS and neurologic events were observed in the ZUMA-1 trial in 32% of treated patients.8 In the JULIET trial, grade 3 CRS and neurologic events occurred in 22% and 12% of treated patients, respectively6; in the ELIANA trial, these cases were 46% and 13%, respectively.7 The expansion and persistence of CAR T cells make it difficult to stop CAR T-cell treatments if toxicity is observed. Lenalidomide can be given with or without rituximab, or along with tafasitamab. The approach allows targeting of several antigens simultaneously to decrease toxicity through an on-off adapter molecule with a short half-life and counteract T-cell exhaustion with treatment-free intervals. DeVita, Hellman, and Rosenbergs Cancer: Principles and Practice of Oncology. CAR T-cell therapy is used to treat certain blood cancers. The time sequence of the reversibility depends on how severe [the toxicity] is. . This article has a companion Point by Molina and Shah. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. Lisocabtagene maraleucel (Breyanzi, also known as liso-cel) is approved to treat adults with diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and follicular lymphoma grade 3B, after at least one other kind of treatment has been tried. There are probably over 30 different companies that are trying to [manufacture] CAR T cells in multiple myeloma. doi: 10.1016/j.chemosphere.2018.06.118. CAR T-cell therapy Tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel) are the 2 CAR T-cell therapies currently approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to treat adult patients with relapsed/refractory (r/r) B-cell malignancies. Your doctor will check your blood cell counts regularly during your treatment. Chimeric antigen receptor (CAR) T-cell therapy: This therapy takes some T-cells from a patient's blood, . This brings the two together, which helps the immune system attack the lymphoma cells. Here the authors present an IgE antibody targeting the melanoma-associated antigen, chondroitin sulphate proteoglycan 4 . Severe nausea, vomiting, and/or diarrhea. CAR T-cell therapy is an exciting area now. There will likely be a lot of competing options for BCMA-directed therapy. Over the course of the past few years, we found that giving combination therapies with multiple mechanisms of action results in superior activity, such that triplets appear to be the standard of care for newly diagnosed patients. However, a direct comparison of the response rates is invalid due to the differences in patients treated in each trial. How has the treatment of multiple myeloma evolved? Polatuzumab vedotin (Polivy) is an anti-CD79b antibody attached to a chemotherapy drug (an antibody-drug conjugate). CAR T cells can persist and expand in patients and are typically given as a single transfusion (as in the ZUMA-1 trial). . However, adverse events of grade 3 or higher occurred in 87% of patients treated with blinatumomab in the TOWER trial, which is lower than observed in the ZUMA-1 trial (95%) and similar to those rates in the JULIET (89%) and ELIANA (88%) trials. 2023 American Cancer Society, Inc. All rights reserved. These other agents have different toxicities profiles and different response rates. Nonetheless, the use of such new drugs to treat solid tumors is not . Besides common therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, novel therapeutic approaches, including immunotherapy, have been an advent in CRC treatment. However, most disease relapses do not feature loss of the target antigen but present with other immune-related escape mechanisms, including the upregulation of inhibitory checkpoint molecules, most commonly PD-L1.28 To reverse this adaptive immune escape mechanism, several antiPD-1 or antiPD-L1 monoclonal antibodies are currently used in combination with blinatumomab and CAR T cells. Tell your health care team right away if you have a fever, cough, chest pain, shortness of breath, sore throat, rash, or pain when urinating. This is quite impressive for a group of patients whose lifespan would be shorter than patients who have not received 4 prior lines of therapy. Some people have infusion reactions while getting this drug, which can cause symptoms like chills, flushing, headache, or shortness of breath during the infusion. Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. This is in sharp contrast to blinatumomab treatment in which responding patients often recover their neutrophil counts while receiving blinatumomab infusion, resulting into a lower rate of short-term infectious complications.4 After either blinatumomab or CD19 CAR T-cell infusion, long-term B-cell aplasia and hypogammaglobulinemia have been reported, although it is more profound after CAR T-cell therapy. doi: 10.3322/caac.21492. Blood Adv 2021; 5 (2): 607612. National Comprehensive Cancer Network (NCCN). With CAR T cells, patients get their therapy, get their response, and may not require treatment for an extended period of time. American Cancer Society medical information is copyrightedmaterial. CAR-T- and a side order of IgG, to go?- Immunoglobulin . This happens most often within the first day after the infusion, and it can be serious or even life-threatening. 2017;377(26):2531-2544. National Comprehensive Cancer Network (NCCN). Age was a particularly variant factor between study cohorts. Both of these approaches have beneficial anti-tumor effects on CRC. Dexamethasone was used in the TOWER trial prophylactically to prevent CRS and neurologic events; thus, blinatumomabs safety in this regard cannot be compared with tisa-cel or axi-cel. Practice Guidelines in Oncology: T-cell Lymphomas. The great advantage of this approach is an increase in the safety profile, as the infusion can be stopped at any time, thereby reversing immune activation and immune-related adverse events. These receptors can attach to proteins on the surface of lymphoma cells. Once connected, it is drawn into the lymphoma cell where the chemo is released and destroys it. Help us end cancer as we know it,for everyone. Checkpoint inhibitors and adoptive cell therapy (ACT) are 2 of the main actors, together with monoclonal antibodies and immunomodulatory agents, in the immune-oncologic approach. BCMA stands for B-cell maturation agent, and all myeloma cells have some expression of BCMA on their cell surface. N Engl J Med. National Library of Medicine Yes, there are some bystander effects with [belantamab mafodotin]. In children and young adults with BCP-ALL with 3 months of follow-up, tisa-cel achieved a CR rate of 81%. The first BCMA-directed therapy that has been FDA approved is belantamab mafodotin. From a hematologic standpoint, it can lower white [blood cell] counts and platelet counts, but that is usually not a major consequence. You can help reduce your risk of cancer by making healthy choices like eating right, staying active and not smoking. An example is blinatumomab (Blincyto), which binds to both CD19, a protein found on the surface of leukemia cells, and CD3, a protein on the surface of T cells. Cancer Information, Answers, and Hope. Accordingly, blinatumomab is the preferred treatment of choice in this situation with high response rates (88/113 patients with MRD conversion) and a favorable safety profile. All the other BCMA-directed therapies require continuous and indefinite therapy until they no longer work. Abeloffs Clinical Oncology. Monoclonal antibodies as immunomodulatory therapy against cancer and autoimmune diseases. Loncastuximab tesirine (Zynlonta):This antibody-drug conjugateis used by itself to treat some types of large B-cell lymphoma (including diffuse large B-cell lymphoma, or DLBCL) after at least 2 other treatments (not including surgery or radiation) have been tried. [The rates are] about 30% to 35% depending on which DREAMM study you look at. -, De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, et al. In the JULIET trial, the median time from enrollment to infusion with tisa-cel was 54 days, and only 111 of 165 enrolled patients received cells.6 Seven percent of patients did not receive the treatment because of manufacturing failure, and an unreported number of patients were ineligible for inclusion in the trial due to low circulating lymphocyte counts. BiTE-based approaches are particularly promising against early-stage disease with low tumor burden (eg, in the MRD setting of BCP-ALL) and a still-functional T-cell compartment. Chapter 103: Non-Hodgkins lymphoma. The American Cancer Society medical and editorial content team. Trouble breathing. Common side effects can include nerve damage (neuropathy), low blood counts, fatigue, fever, nausea and vomiting, infections, diarrhea, and cough. Marion Subklewe; BiTEs better than CAR T cells. [Moreover,] there is at most a 10-day window in which these. On average, patients stay in remission for 2.5 to 5 years. 2019;11:164. doi: 10.3390/nu11010164. We didnt have that option when I started. On the other hand, T cell activation by genetically engineered CAR receptor via the TCR/CD3 and costimulatory domains can induce potent immune responses against specific tumor-associated antigens (TAAs). Youll likely get medicines before treatment to help lower this risk, but its important to tell your healthcare provider right away if you have any of these symptoms. David H. Vesole, MD, PhD, discusses the evolution of multiple myeloma treatment, and explained how other BCMA-therapies are poised to impact clinical practice. A 54% (7/13) ORR (including 5 CRs and 2 PRs) . Other monoclonal antibodies bring T cells close to cancer cells, helping the immune cells kill the cancer cells. The strategy of combining targeting tumor antigens has also been applied to chimeric antigen receptor (CAR) T cell therapy and is a promising immunotherapy for several malignancies, such as . Chapter 106: Non-Hodgkin Lymphoma. This approach enables escalation of the titrated BiTE dose while maintaining a favorable safety profile. Mosunetuzumab (Lunsumio) is a type of antibody known as a bispecific T-cell engager (BiTE). 2018. Furthermore, T-cell subset composition and function determine the response to BiTE treatment.32,33 However, in the case of CAR T cells, T-cell composition and function at time of leukapheresis also influence CAR T function and are further modulated through patient- and disease-related parameters after transfusion. Blinatumomab was given to adults with a median age of 41 years, whereas the median age in the ELIANA trial was 11 years. For reprint requests, please see our Content Usage Policy. This drug is infused into a vein (IV), typically every 3 weeks. We couldnt do what we do without our volunteers and donors. It wasnt until proteasome inhibitors (PIs), which were enzyme-specific pathway inhibitors that were first approved in 2003, that we started [using] targeted therapies for specific pathways and cells. 2) in that they can: 1) redirect specific polyclonal immune cells such as T cells and NK cells to tumor cells to enhance tumor killing, 2) simultaneously block two different pathways with unique or overlapping functions in pathogenesis, 3) potentially increase binding specificity by Tisa-cel can also be used on a pediatric population and is indicated for patients <26 years with r/r B-cell precursor acute lymphoblastic leukemia (BCP-ALL).3 Currently, the only BiTE with FDA and EMA approval is blinatumomab, which redirects CD3+ T cells to CD19+ leukemic blasts. Possible side effects include local skin reactions, like redness, where the drug is injected, infections, low white blood cell counts, nausea, fatigue, and constipation. Our group is heavily biased toward stem cell transplants, which is considered standard of care throughout the world. Allogeneic CAR-T cells: More than ease of access? Monoclonal antibodies are. They demonstrated remarkable efficacy in B cell hematologic malignancies, thus paving the way for their development in solid tumors. Careers. Optimized CAR T-cell logistics, including an increase in the number and sites of production, as well as changes in ex vivo culture time, will most likely shorten the time from harvesting to infusion.9 In contrast, BiTEs are recombinant proteins that can be manufactured in large quantities without interpatient variability and can be rapidly used once the indication has been determined by the clinician, independent of peripheral lymphocyte counts. This type of treatment enhances the ability of your T cells to recognize and attack cancer cells. Over recent years, bispecific antibodies have been engineered in >50 different formats, including dual-affinity retargeting proteins, tandem diabodies, and bi-nanobodies, but in oncology, the bispecific T-cell engagers (BiTEs) are the most developed and thus are the focus of this article.1 Both BiTE and CAR approaches are independent of the specificity of the endogenous T-cell receptor and independent of major histocompatibility complex on tumor cells. antibodies targeting immune checkpoints, bispecific antibodies, and chimeric antigen receptor [CAR]-T cells), is raising questions on their potential immunogenicity and effects on treatment. DREAMM-6 was presented at [the 2020 ASCO Virtual Scientific Program] in June, showing response rates north of 30% with the addition of bortezomib (Velcade), [which is] far superior [than what weve seen with belantamab mafodotin alone]. The investigators are giving individual drugs, based on the patients DNA sequencing, that will attack specific abnormalities. Ive been caring for patients with multiple myeloma for over 30 years, and treatments have evolved tremendously over the years. Antigenized antibodies Antigenization is an investigational approach in which an mAb can be engineered to deliver an antigen (eg, as a vaccine). Are BiTEs better than CAR T approaches? Although the production process is well established, it is only feasible in patients with sufficient peripheral counts, and each treatment involves several steps, each of which carries the possibility of error. The use of adapter CAR T cells is aimed at combining the benefits of BiTE molecules with the power of ex vivoactivated CAR T cells. The blood of the patient is collected and, Five generations of CAR-T cells. Bispecific proteins (recombinant proteins that simultaneously bind 2 different antigens) and chimeric antigen receptors (CARs) facilitate T-cellmediated killing of malignant cells by redirecting autologous T lymphocytes to cell-surface antigens on cancer cells. Back in the day, all of our drugs were chemotherapies, which have a lot of bystander effects and can cause nausea and vomiting. official website and that any information you provide is encrypted Similar to the DREAMM studies, these agents are being combined with many of the standard therapies that we currently use. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf on May 2, 2018. Together, were making a difference and you can, too. Other side effects can include feeling tired, rash, fever, and headache. However, the BiTE platform offers a higher flexibility for combinatorial and sequential approaches from a toolbox of targeting and immunomodulatory antibody constructs. Park et al22 reported on long-term follow-up of CD19-CD28 CAR T cells in a pediatric BCP-ALL population (n = 53). [Both] are BCMA-directed therapies. Right now, belantamab mafodotin is being given as a single agent. and with tocilizumab, an anti-IL-6 monoclonal antibody. Conflict-of-interest disclosure: M.S. Clearly, challenges in production, manufacturing, and safety should be balanced against response rates. What challenges remain with regard to treatment in multiple myeloma? CAR T-cell therapy can cause toxicities, but in contrast to lymphoma and leukemia, most of them are minor in multiple myeloma. In a preclinical model, dasatinib, an FDA-approved tyrosine kinase inhibitor, suppressed CAR T-cell activation via rapid and reversible antagonism of the CAR CD3 chain, thereby diminishing exhaustion marker expression and restoring functionally.35 This work demonstrated the potential to reinvigorate CAR T-cell function through drug-induced T-cell reprogramming. More serious side effects include infection, fluid collection in the lungs, around the heart, or in the abdomen (belly), very low blood counts, and very severe skin reactions when out in the sun. Although they share a common antigen target in the B-cell lineage surface protein CD19, they differ in their intracellular costimulatory domain (4-1BB vs CD28). All of these drugs can cause inactive hepatitis B infections to become active again, which can lead to severe or life-threatening liver problems. Now, we are approaching potentially achieving CRs in 80% or more of patients depending on the regimen that we utilize. Scott AM. Immune system cells normally have substances that act as checkpoints to keep them from attacking other healthy cells in the body. Tax ID Number: 13-1788491. Nervous system problems: This drug might affect the nervous system, which could lead to symptoms such as headaches, numbness or tingling in the hands or feet, feeling dizzy or confused, trouble speaking or understanding things, abnormal sleep patterns, tremors, or seizures. Ultimately, this is what is going to happen. CEA plasmid as therapeutic DNA vaccination against colorectal cancer. DREAMM-2 is the phase 2 trial that led to the FDA approval for the drug. Monoclonal antibodies can help fight cancer in different ways. In chimeric mAbs, the variable regions of a mice Ab is fused with the constant regions of a human Ab. Although quadruplets are quite effective up front, they are not FDA approved at this point in time. AE, adverse event; ICU, intensive care unit; IgG, immunoglobulin G; Ph, Philadelphia chromosome; PMBCL, primary mediastinal B-cell lymphoma; SOC, standard of care; Tx, treatment; WBCs, white blood cells. In this treatment, immune cells called T cells are removed from the patients blood and altered in the lab to have specific receptors (called chimeric antigen receptors, or CARs) on their surface. The most advanced construct, the CD20 CD3 T-cellbispecific mosunetuzumab, has a rendered ORR of 37% in aggressive lymphoma with a CR rate of 19%.19 Several other clinical trials are currently recruiting patients for single or combinatorial approaches. sharing sensitive information, make sure youre on a federal Although this occurs in about 80% of patients treated with the drug, severe reactions occur in about 10% of patients. Researchers are still studying this type of therapy and other ways of changing T cells to treat cancer. Common adverse events of BiTE and CAR T-cell therapies are cytokine release syndrome (CRS) and immune effector cellassociated neurotoxicity syndrome (ICANS). Mosunetuzumab can be used to treat follicular lymphoma that has returned or that is no longer responding after treatment with at least 2 other types of drugs. Bookshelf Large B-cell lymphoma (including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and diffuse large B-cell lymphoma arising from follicular lymphoma) that hasnt responded to initial treatment with chemotherapy plus immunotherapy, or that comes back within a year of this treatment. Yet those productswhich include cell therapies, such as chimeric antigen receptor (CAR) T-cell therapy for aggressive B-cell lymphomas, and gene therapies to treat a range of monogenic rare diseaseshave proved transformative for patients. The CAR T-cell technology continues to improve. CAR T-Cell Therapy - Explained Monoclonal Antibodies The Success Story of Herceptin Cancer Basics From the day you were conceived, your body has been busy dividing its cells rapidly and today you are comprised of 37 trillion cells of different form and function. as well as follicular lymphoma that hasnt responded to or has come back after other therapies,after trying at least two other kinds of treatment. government site. #mmsm. 10th ed. The agent was only tested in patients who had 4 or more lines of therapy. Accessibility These drugs can also increase your risk of certain serious infections for many months after the drug is stopped. The FDA approval of belantamab mafodotin was based on data from the DREAMM-2 trial. 2018; 41:114-121. How do you see CAR T-cell therapy impacting the landscape of multiple myeloma? Chimeric antigen receptor (CAR) T cells; Colorectal cancer; Immunotherapy; Monoclonal antibody. This drug is infused into a vein (IV), typically about once a week for the first few months, and then once every two weeks. Herein, we review the different mAbs against various pathways and their applications in clinical trials, the different types of CAR-T cells, various specific CAR-T cells against TAAs, and their clinical use in CRC treatment. Unauthorized use of these marks is strictly prohibited. We are not sure if they will be covered by third-party carriers. The data strongly support the use of blinatumomab in MRD-positive patients with BCP-ALL. Pharmacological immunosuppression, such as using tocilizumab and/or corticosteroids, is necessary to manage these toxicities.13 In contrast, because of its short half-life, blinatumomab treatment can be interrupted or discontinued if necessary, without prolonged effect. This drug can cause some of the same side effects as other antibodies that target CD20, including infusion reactions (see above). Right now, we have the option to make this a chronic disease in the same way high blood pressure or diabetes [are chronic diseases]. The https:// ensures that you are connecting to the It is approved for use in patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia. Accessed at https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq on May 3, 2018. One can speculate that individualized biomarkers encompassing disease-, immune-, and patient-related parameters will guide personalized BiTE-based combinatorial approaches toward optimized safety profiles and response rates. I imagine that in the future, patients are going to get 4 or 5 different drugs, some specific to enzyme pathways, others specific to their individual DNA sequencing. However, the dose of CAR T cells used in these trials varies and also differs among recipients within a single trial. IgE antibodies targeting cancer antigens can be used for immunotherapy. FOIA Accessed at https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf on May 2, 2018. MAbs demonstrate the great ability to completely recognize cancer cell-surface receptors and blockade proliferative or inhibitory pathways. Whereas both these platforms use single-chain variable fragments to recognize and target antigens expressed on tumor cells, the BiTE platform also uses one to recognize and bind T cells.2, Tisagenlecleucel (tisa-cel) and axicabtagene ciloleucel (axi-cel) are the 2 CAR T-cell therapies currently approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to treat adult patients with relapsed/refractory (r/r) B-cell malignancies. Rare but serious side effects can include strokes, as well as tears in the blood vessels in the head and neck. Although this is the first approved [BCMA-directed] drug, there are a lot of other therapies directed against BCMA that have different toxicity profiles than belantamab mafodotin. Practice Guidelines in Oncology: B-cell Lymphomas. Other diseases have ADCs as well, but [belantamab mafodotin] is the first approved in multiple myeloma. This drug is infused into a vein (IV), typically every 3 weeks. -. Philadelphia, Pa: Elsevier; 2014. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Tumor flare: This drug might cause your tumor to grow or cause more symptoms for a time, which is known as tumor flare. A number of monoclonal antibodies target the CD20 antigen, a protein on the surface of B lymphocytes. Version 3.2018. Vesole: All patients with multiple myeloma are BCMA positive. Would you like email updates of new search results? The new monoclonal and bispecific antibodies and CAR-T, besides offering new perspectives in the overall survival and disease-free survival of patients, may also transform the epidemiology of infections in ALL by improving the toxicity of treatments. and transmitted securely. 2010;11:753762. However, adapter kinetics, target antigen affinities, and antigen sinks are challenges that need to be overcome.36. The first-generation CAR-T cells only contain one intracellular, MeSH most of these therapies can be given with the prolongation of life, without negatively impacting QOL a great deal.. Given this risk, the company that makes these drugs puts restrictions on access to them to prevent women who are or might become pregnant from being exposed to them. Please enable it to take advantage of the complete set of features! Studies evaluating these allogeneic. Your health care team will watch you closely for possible signs of CRS, especially during and after the first few infusions. The combination of BiTEs as an adapter strategy for CAR T cells is currently being tested in early clinical trials. This site needs JavaScript to work properly. In the TOWER trial of blinatumomab, patients received 2 cycles of induction therapy followed by up to 3 cycles of consolidation therapy if necessary and then 12 months of maintenance therapy. T cells are removed from a patient through a process like a blood draw. Blood Cancer J. These drugs can cause severe birth defects if taken during pregnancy. It can take 5-7 minutes to inject the drug, but this is much shorter than the time it normally takes to give the drug by vein. Antibiotic and antiviral medicines are given to help protect against them, but severe and even life-threatening infections can still occur. Thus, the overall safety profile appears to be better for BiTE molecules than for CAR T cells. CAR-T cell therapy: current limitations and potential strategies. The induction and consolidation therapies were 6-week cycles consisting of 4 weeks on and 2 weeks off, whereas the maintenance therapy was 4 weeks for every 12 weeks. Then we come back with salvage therapy, usually with triplet regimens, of which there are a number approved by the FDA for patients who have had 1 to 3 prior lines of therapy. Because of these kinds of reactions, drugs to help preventthem aregiven before each infusion. The DREAMM series is an ongoing effort to improve the outcome of single-agent belantamab mafodotin. Other side effects can include low blood cell counts (with an increased risk of bleeding and serious infections), feeling tired or weak, loss of appetite, diarrhea, cough, fever, and swelling in the hands or legs. Currently, blinatumomab is the only approved drug for treatment of MRD-positive BCP-ALL. Bethesda, MD 20894, Web Policies Other novel formats, such as the multifunctional antibody construct that targets a tumor-associated antigen with high affinity and blocks an inhibitory checkpoint molecule with low affinity, will be tested.29 Alternative constructs elicit a combination of simultaneous blockade of immune checkpoint molecules and costimulation30 or provide targeting and stimulating within one construct.31 Also, the CAR T-cell platform enables different strategies to be used to block the inhibitory PD-1 signal, including CRISPR-Cas9mediated PD-1 disruption.
