Balancing the CAR T: Perspectives on Efficacy and Safety of CAR T-Cell Therapy in Hematologic Malignancies

Supplements and Featured Publications, Optimizing the Value of CAR T-Cell Therapy: Managed Care Considerations From Recent Clinical Findings, Volume 27, Issue 13


Chimeric antigen receptor (CAR) T-cell therapy is an example of how immunotherapy is revolutionizing the treatment of hematologic malignancies with unprecedented response rates in patients with relapsed/refractory lymphoma, multiple myeloma, and acute lymphoblastic leukemia. The process for administering CAR T-cell therapy is complex, with multiple steps including CAR T-cell manufacturing, lymphodepleting chemotherapy, cellular therapy infusion, and management of short-term and long-term toxicities. While effective, broad use of CAR T-cell therapies is limited by potential for life-threatening toxicities, challenges related to manufacturing a patient-specific product, high costs and inadequate reimbursement, and incomplete or unsustained disease response. Pharmacists are intricately involved in the process of providing CAR T-cell therapy both at the organizational level of budgeting and coordinating therapy and in direct patient care roles providing counseling and support for adverse effect management. Research in CAR T-cell therapy is expected to improve tolerability and expand indications to more types of malignancies and earlier phases of disease. Managed care professionals should have an understanding of the clinical trial data and place in therapy in lymphoma, myeloma, and acute lymphoblastic leukemia as well as guideline recommendations for adverse effect management associated with CAR T-cell therapies.

Am J Manag Care. 2021;27(13):S243-S252.

Chimeric Antigen Receptor (CAR) T-Cell Therapy

Innovations in immunotherapy have led to the development of multiple immune-targeted therapies to manage malignancy. Chimeric antigen receptor (CAR) T-cell therapy is designed to enhance the body’s immune system to effectively kill malignant cells.1 CAR T-cell therapy pivotal trials demonstrated unprecedented overall response rates (ORRs) and complete responses (CRs) that led to the FDA approval of 5 CAR T-cell products: tisagenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), brexucabtagene autoleucel (brexu-cel), and idecabtagene vicleucel (ide-cel). CAR T-cell therapies are limited by the potential to cause life-threatening toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In addition, challenges related to manufacturing a patient-specific product, need for inpatient administration in a tertiary care setting, high costs and inadequate reimbursement have limited access to CAR T-cell therapy.2,3 Cellular therapy centers, manufacturers, payers, and policy makers will need to work together to address barriers to care as new CAR T-cell products with improved efficacy and tolerability are approved for use in more diverse malignancies.2

Mechanism of Action

CAR T cells are T cells that have been genetically modified through transfection (DNA plasmid inclusion) or transduction (using viral vector) to transmit genes that will produce a new antigen recognition domain on the T-cell surface to facilitate cancer cell detection.4,5 The CAR molecule consists of 3 parts: (1) an extracellular, antibody-derived, single-chain variable fragment to bind a specific antigen on the tumor cell with a hinge region, (2) a transmembrane domain (part of CD3, CD8, CD28, or FcεRI) and (3) an intracellular domain, consisting of the intracytoplasmic activating domain (CD28, CD27, CD134, CDB7, or CD3ζ) derived from the T-cell receptor with or without a second costimulatory factor (CD28 or 4-1BB) (Figure 14). CAR T cells bind antigens independent of human leukocyte antigens (HLAs), an important feature because HLA downregulation is a key mechanism of cancer cell escape from immune surveillance.5 Antigen escape and lack of CAR T-cell persistence are the most common causes of relapse after CAR T-cell therapy. CAR T-cell products currently approved by the FDA are considered “second generation” because they include an additional costimulatory domain such as 4-1BB or CD28 to improve persistence and potency.1 To further augment the antitumor activity, a third-generation CARis being developed with multiple costimulatory domains and a fourth-generation CAR contains a transduction domain to promote production of a T-cell−activating cytokine such as interleukin (IL)-1.6 Strategies to reduce CAR T-cell–mediated toxicity include modifying the CAR hinge, transmembrane regions, or costimulatory domain; utilizing human/humanized antibody fragments instead of murine-derived CARs; including an “off switch”; and inhibiting macrophage and monocyte-activating cytokines.7

Manufacturing/Administration Process

Currently FDA-approved, CAR T cells are manufactured from autologous T cells, collected from the patient via leukapheresis (Figure 26).5,6 Manufacturing CAR T cells takes 2 to 4 weeks, during which time the cells undergo gene modification, expansion ex vivo, and freezing for subsequent re-infusion. The patient-specific CAR T-cell product is then transferred back to the hospital and is re-infused into the patient.6 Patients receive lymphodepleting chemotherapy to enhance CAR T-cell expansion, proliferation, and persistence. Patients typically receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide 2 to 14 days before receiving CAR T-cell infusion.3,8 After CAR T-cell infusion, the chimeric receptor recognizes an antigen leading to effector cell activation, proliferation, and a milieu of cytokine release including IL-6, soluble IL-6 receptor, soluble IL-2Ra, interferon gamma (IFN-g), and granulocyte-macrophage colony-stimulating factor (GM-CSF).8

Historically, CAR-T cell patients were observed in hospital after administration to monitor for development of toxicities including CRS.3 With more experience, a more predictable clinical course, enhanced multidisciplinary care, and desire to minimize overall costs, there is growing interest in and increasing evidence supporting outpatient administration with appropriate thresholds for hospital admission if symptoms, such as fever, occur.9 Risk Evaluation and Mitigation Strategy (REMS) programs for CAR T-cell therapy require patients to remain within 2 hours of the certified hospital (although some centers elect a smaller radius of 30-60 minutes) and its associated clinics for at least 4 weeks following CAR T-cell infusion. In addition, patients must have a dedicated caregiver present from the start of lymphodepleting chemotherapy through at least 30 days after infusion, and driving is restricted for the first 8 weeks following infusion.3 Patients who do not reside near the certified hospital will need to arrange for temporary housing.

FDA-approved CAR T-Cell Therapies in Hematologic Malignancies

Non-Hodgkin Lymphoma

Large B-cell lymphoma (LBCL)

Approximately 30% of patients with LBCL relapse after initial therapy or after salvage autologous stem cell transplant and may benefit from CAR T-cell therapy in the third-line setting.10,11 CAR T-cell therapy is considered standard of care for any patient with LBCL (de novo or transformed) in whom at least 2 prior lines of standard therapy have failed.12 Overall response rates to CAR T-cell therapy in LBCL range from 52% to 82% with CR rates of 40% to 49% and are summarized in Table 1.13-22 Results of CAR T-cell trials must be interpreted carefully as just 47% of patients screened for CAR-T cell therapy in JULIET actually received therapy; 15% of patients in TRANSCEND-NHL-001 and 9% in ZUMA-1 underwent leukapheresis but did not receive CAR T-cell therapy.13,17,19 Insurance approvals, prior authorizations, high cost and inadequate reimbursement, travel to tertiary centers, limited apheresis slots, and manufacturing delays/failures are barriers to receipt of CAR T-cell therapy.2,23,24 In addition, patients in the phase 2 ZUMA-1 study of axi-cel were not allowed to receive bridging therapy; thus, patients with rapidly progressive disease would therefore not have been eligible because they would not have been able to wait for 3 weeks between apheresis and CAR T-cell treatment.13 Both the JULIET and TRANSCEND-NHL-001 studies allowed bridging therapy.17,19 Of the 3 CAR T-cell studies in LBCL, the TRANSCEND-NHL-001 study is noteworthy for having broad enrollment criteria, allowing patients with low creatinine clearance, poor cardiac function, low absolute lymphocyte count, and high-risk features such as central nervous system involvement to be enrolled.19 Real-world, postmarketing data of 1000 patients treated with axi-cel showed results similar to those of the clinical trials, with a 70% ORR and a CR of 53%.25 A recent matching-adjusted indirect comparison of individual patient-level data from JULIET and TRANSCEND-NHL-001 patients found no evidence to suggest differences in overall survival (OS), progression-free survival (PFS), and CR between tisa-cel and liso-cel in relapsed/refractory LBCL.26 There is also growing evidence to support the use of CAR T-cell therapy in the second-line setting. Early results for ZUMA-7, a randomized phase 3 trial of axi-cel versus second-line standard of care including consolidative autologous stem cell transplantation, show that CAR T-cell therapy improves event-free survival (EFS) in LBCL. Currently, these results are only available through press release and notably the data are immature and there is no overall survival benefit at this time.27 TRANSFORM (NCT03575351), a randomized, multicenter phase 3 study comparing liso-cel with salvage therapy followed by high-dose chemotherapy and autologous stem cell transplant as second-line treatment in adults with relapsed or refractory LBCL, lists a primary completion date of 2023. In press release only, it was announced that this study met its primary end point of demonstrating a clinically meaningful and highly statistically significant improvement in EFS, as well as secondary end points of complete response rate and PFS compared with salvage. Specific results were not released and data are considered immature until published in a peer-reviewed journal.28

Mantle cell lymphoma

Patients who have disease progression after receipt of Bruton tyrosine kinase inhibitors have poor outcomes with an objective response occurring in 20% to 86% of patients and a median OS of 6 to 24 months.29-31 Brexu-cel is an anti-CD19 CAR T-cell product that removes circulating CD19-expressing malignant cells during the manufacturing process, allowing it to be used in patients with leukemia or mantle cell lymphoma.21 In the patients treated with brexu-cel in the ZUMA-2 study, 93% had an objective response and 67% had a CR.21 At 12 months, the estimated PFS and OS were 61% and 83%, respectively, in the ZUMA-2 study.21

Follicular lymphoma

Most patients with follicular lymphoma have an indolent disease pattern of relapsing and remitting. Nevertheless, approximately 20% of patients will relapse within 2 years of front-line therapy and based on the LymphomaCare study, patients with early relapse have a significantly worse 5-year survival (50%) compared with those who do not (90%).32 Both axi-cel and liso-cel are approved by the FDA for management of patients with follicular lymphoma based on ORR of 84% to 95% and CR rates of 63% to 80%.16,19 Tisa-cel has been evaluated in patients with follicular lymphoma as well.33 Longer follow-up is needed in follicular lymphoma to determine if a subset of these patients are cured; however, some patients receiving CD19 CAR T-cell therapy remain in remission after more than 5 years.16,34

Acute Lymphoblastic Leukemia

Historically, outcomes in adults with relapsed/refractory acute lymphoblastic leukemia (ALL) are poor, with a median OS fewer than 6 months and attainment of complete remission in only 20% to 40% of adults.35 Inotuzumab ozogamicin and blinatumomab have significant activity in this population with CR observed in 36% to 81% of patients and median OS of 7 to 8 months.36-38 The National Comprehensive Cancer Network (NCCN) guideline panel for ALL considers inotuzumab ozogamicin and blinatumomab category 1 recommendations for relapsed/refractory ALL and tisa-cel a category 2A recommendation.39 Tisa-cel was approved by the FDA for patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse.18 The approval was based on the phase 2 ELIANA study of 75 patients with a median age of 11 years who received tisa-cel after a median of 3 previous therapies.40 A CR or CR with incomplete hematologic recovery was reported in 81% of patients receiving tisa-cel and all of those patients achieved minimal residual disease-(MRD) negativity (Table 218,40). At 12 months, the EFS was 50% and OS was 76%. A phase 3 trial to compare tisa-cel with blinatumomab or inotuzumab ozogamicin in adult patients with relapsed/refractory B-cell ALL was planned (NCT03628053); however, the study is no longer being pursued because of planned investigation of novel CAR T-cell therapies in this patient population.41 A phase 2 study (ZUMA-3) of brexu-cel in 55 adult patients with relapsed or refractory ALL reported a CR or CR with incomplete hematologic recovery in 71% of patients, CR in 56%, median relapse-free survival of 11.6 months, and median OS of 18.2 months.42 MRD-negativity was achieved in 76% of patients receiving brexu-cel.42 A biologics license application (BLA) has been submitted to the FDA for brexu-cel in adult patients with relapsed or refractory ALL.43 Similar to studies in lymphoma, not all enrolled patients received therapy, with approximately 18% not receiving tisa-cel and 22.5% not receiving brexu-cel in ELIANA and the ZUMA-3 studies, respectively.40,42

Multiple Myeloma

The treatment landscape of multiple myeloma changes rapidly with multiple new effective therapies approved in the past few years; however, the disease remains incurable.3 Responses and median PFS vary widely based on multiple factors including transplantation status, number of previous lines of therapy, and the salvage regimen used.3 Patients who develop resistance to multiple agents including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody have a poor prognosis, with survival less than 1 year.44 The KarMMa study evaluated 128 patients receiving ide-cel for relapsed/refractory myeloma after a median of 6 prior regimens including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.45 Nine percent of enrolled patients did not receive therapy. An ORR of 73% was observed with ide-cel; 33% of patients achieved a CR and 26% of patients attained MRD-negativity (Table 345-48). In this heavily pretreated population, the median PFS was 8.8 months and median OS was 19.4 months. Ide-cel is included in the NCCN guidelines as an “other recommended regimen” (category 2A recommendation) for patients who have received at least 4 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody, and is approved by the FDA in this population.49

Ciltacabtagene autoleucel is another promising CAR T-cell product for patients with relapsed/refractory multiple myeloma. A phase 1b study of ciltacabtagene autoleucel evaluated 97 patients with relapsed/refractory myeloma after a median of 6 prior regimens including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 antibody.47 The ORR was 97% and CR was observed in 67% of patients; 12-month PFS and OS were 77% and 89%, respectively. The FDA has accepted a BLA priority review for ciltacabtagene autoleucel with a Prescription Drug User Fee Act target action date of November 29, 2021.48 Phase 3 clinical trials are ongoing to compare CAR T-cell therapy versus standard-of-care regimens in patients in earlier stages of multiple myeloma and newly diagnosed patients with high-risk cytogenetic profiles or with residual disease after transplantation.44

Role of Clinical Pharmacists

Clinical pharmacists are involved in multiple aspects of CAR T-cell therapy. Pharmacists should complete adetailed patient profile review and medication reconciliation to evaluate for potential drug−drug interactions before lymphodepletion and CAR T-cell infusion.3 It is highly recommended that a cellular therapy clinical pharmacist provide patient education on the rationale for and potential toxicities of lymphodepleting chemotherapy and the cellular therapy product; this service is a way to meet the REMS component of providing patients with a REMS wallet card.3 The cellular therapy pharmacist typically coordinates with information technology to develop electronic order sets that include lymphodepletion, cellular therapy product, ancillary supportive care, and toxicity management. Pharmacists verify orders of lymphodepleting therapy and may be involved in labeling of the product at some centers.3 Pharmacists may facilitate documentation in the electronic medical record of the availability of at least 2 doses of tocilizumab that can be administered within 2 hours of cellular infusion for each patient receiving CAR T-cell products, another component of REMS program documentation for commercially available CAR T-cell products.3 Given the toxicity profile of CAR T-cell therapy, pharmacists are essential in adverse effect management. Lastly, pharmacists in the CAR T-cell therapy process play a valuable role in budgeting and purchasing given the cost of a single dose of CAR T-cell therapy is estimated between $373,000 and $475,000 per infusion.2,3

Outpatient management

There are many factors (disease specific, patient specific, cellular therapy specific, and institution specific) that influence the decision for inpatient versus outpatient administration of CAR T-cell therapies.9 As experience grows and newer constructs are developed that minimize or delay toxicity, they are more likely to be administered in the outpatient setting.3 The TRANSCEND-NHL-001 study (liso-cel) allowed outpatient administration and approximately 10% of patients received therapy in the outpatient setting.19 Of those patients, 18 (72%) were subsequently hospitalized for adverse effects including CRS, neurological events, or both. Preliminary results from a phase 2 study, OUTREACH (liso-cel) in the nonuniversity setting indicates similar safety data for inpatients and outpatients, with early (on or before study day 4) and overall hospitalization in outpatients reported in 27% and 63%, respectively.50 The median time to hospitalization was 5 (range, 2-61) days and median length of stay was 6 (range, 1-28) days. As use of CAR T-cell therapy continues to expand, changes in payment models, care settings, or both are needed to ensure the sustainability of safe, efficient, and cost-effective treatment.3

CAR T-Cell Toxicity

Overall, the likelihood of CAR T-cell–associated toxicities is high and not all patients can tolerate therapy. The incidence and severity of CRS and ICANS varies with CAR T-cell product and disease
(Table 43,4,14,16,17,19,21,40,42,45,47).

While the risk of early death was less than 3% in clinical trials, an analysis based on the FDA adverse event reporting system, including more than 1000 patients treated with tisagenlecleucel or axi-cel, found 7% of patients died due to nonrelapse mortality within 30 days of initial CAR T-cell administration.51 The most frequent, expected toxicity observed in the week after lymphodepleting therapy is myelosuppression.8 Prolonged cytopenias (more than 28 days) have been described in about one-third of patients receiving tisagenlecleucel or axicabtagene ciloleucel.8,52 Granulocyte colony-stimulating factors should be considered for patients with persistent neutropenia (absolute neutrophil count <500 cells/μL) after day 28 following CAR T-cell infusion, and may be used after day 14 to facilitate neutrophil recovery in the absence of CRS symptoms.34

Antiviral prophylaxis with acyclovir or valacyclovir to prevent herpesviruses should be considered starting with lymphodepleting chemotherapy before CAR T-cell infusion and continuing for at least 6 months post CAR T-cell therapy.34,53 Antimicrobial prophylaxis and antifungal prophylaxis may be considered during periods of severe neutropenia and during periods of persistent neutropenia.34,54 Mold prophylaxis may be considered in high-risk patients requiring treatment of CRS or ICANS.53,54 Prophylaxis against Pneumocystis jirovecii pneumonia should be provided through at least 6 months after CAR T-cell infusion.34,54

CAR T-cell therapy is also associated with unique acute toxicities that need specialized monitoring and management, including CRS, ICANS, and hemophagocytic lymphohistiocytosis (HLH).8,55,56 The American Society for Transplantation and Cellular Therapy (ASTCT) published consensus criteria for grading for CRS and ICANS.57 Management guidelines for patients receiving CAR T-cell therapy do not differ based on the underlying disease, construct, or product used.8 While there are consensus guidelines for grading CRS and ICANS, evidence-based guidelines for management of these toxicities are not universally endorsed.52 The NCCN guideline and Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events recommendations for management of CAR T-cell-related toxicities may be used to guide treatment.34,58 In the absence of randomized trials to support treatment recommendations for CAR T-cell toxicities, institutional management protocols vary at different centers.1


CRS is observed in the majority of patients receiving CD19- and B-cell maturation antigen (BCMA)-directed CAR T-cell products. Symptoms of CRS include fever, hypotension, and hypoxia, and typically present within 2 to 5 days after CAR T-cell therapy.19,58 CRS symptoms may last 7 to 9 days and patients may subsequently develop arrhythmias, cardiomyopathy, prolonged QTc, heart block, renal failure, pleural effusions, transaminitis, and coagulopathy.57,58

CRS prophylaxis with tocilizumab has been shown to reduce the rate of severe CRS and end-organ dysfunctions without affecting expansion, persistence, and response rates of CAR T cells.52 Concerns remain over ablation of the cytokine milieu necessary for CAR T-cell proliferation and activity as well as an increased risk of neurotoxicity with prophylactic tocilizumab.52 Prophylactic use of tocilizumab has not been addressed in current CRS management algorithms and is therefore not recommended.34,52

Supportive care with antipyretics, hydration, supplemental oxygen, and vasopressors should be provided as needed for CRS.52 Two monoclonal antibodies that target the IL-6 receptor, siltuximab and tocilizumab, have been used to manage CRS and tocilizumab is approved by the FDA for treatment of CRS in patients receiving CAR T-cell therapy.8 Recommendations vary for timing of initiation of tocilizumab with some recommending at grade 2 CRS in adults and others for grade 1 or 2 CRS in patients with persistent fever or hypotension refractory to fluids.34,58 Tocilizumab is routinely used for patients with grade 3 or 4 CRS.8,34,58 Corticosteroids have been used to treat severe CRS unresponsive to tocilizumab.1,34,58 In addition, a study proving early steroid therapy when patients have grade 1 CRS or ICANS was associated with a lower rate of grade 3 or 4 CRS or ICANS in patients receiving axi-cel.59 Lenzilumab, anakinra, etanercept, ruxolitinib, itacitinib, ibrutinib, defibrotide, and suicide genes are in clinical trials to determine their role in mitigating CAR T-cell toxicities.1


Neurotoxicity, also known as ICANS, is also frequently observed after CAR T-cell therapy. ICANS is defined as a pathologic process involving the central nervous system following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells.57 ICANS may manifest as delirium, encephalopathy, aphasia, lethargy, difficulty concentrating, agitation, tremor, seizures, and/or cerebral edema.8,57 Typical time to onset is 4 to 10 days; however, onset may be delayed after CAR T-cell infusion.8,57,58 Many patients also have headaches, although this alone does not establish ICANS.57 Symptoms typically last for 14 to 17 days.58 Baseline characteristics predictive of subsequent ICANS development include younger patient age, B-cell ALL, high marrow disease burden, high CAR T-cell dose, and preexisting neurologic comorbidity.1 IL-2 and IL-5 at day 3 post-CAR T-cell infusion were also predictors of severe ICANS development.1

Treatment with corticosteroids (dexamethasone preferred) with dose intensity relative to the severity of ICANS is recommended for management of grade 2 or higher ICANS.8,34,58 The SITC guidelines acknowledge a lower risk for complications with 4-1BB CAR T-cell products and indicate steroids may not be required for grade 2 ICANS with those products.34 Acetazolamide, hyperventilation, and hyperosmolar therapy may be needed to manage elevated intracranial pressure. Electroencephalography is recommended to document seizures, and antiseizure prophylaxis with levetiracetam is commonly used with agents with a higher risk of ICANS.1,8 Levetiracetam is recommended for management of seizures in patients with ICANS.34 CRS does not always develop in patients who develop ICANS; however, if both are present, tocilizumab should be administered.58

Hemophagocytic lymphohistiocytosis (HLH)

HLH, also known as macrophage activation syndrome,is caused by proinflammatory cytokine release by cytotoxic T cells and subsequent natural killer cell stimulation of persistent macrophage activation with hemophagocytosis.8 This results in end-organ tissue damage resulting in kidney injury, liver failure, pancytopenia, and depressed mental status. HLH overlaps with CRS and a consensus on the diagnosis of HLH in CAR T-cell−treated patients has not yet been reached.8 If HLH does not respond to tocilizumab, an etoposide-based regimen is typically given.8,58 There may also be a role for other agents such as anakinra in managing HLH.60

B-cell aplasia

B-cell aplasia is a significant off-tumor direct toxicity from effector cells that often leads to hypogammaglobulinemia. B-cell aplasia can be prolonged, with persistence noted in some patients for at least 4 years. Some clinicians, especially in the pediatric setting, provide replacement therapy with intravenous immunoglobulin infusions, noting that children have fewer established plasma cell clones and might be more susceptible to infections than adults.8,53 The NCCN guidelines panel recommends intravenous immunoglobulin replacement only in patients with recurrent, serious infections and a serum immunoglobulin G level less than 400 to 600 mg/dL.58

Future Directions

There is significant effort worldwide to develop novel CAR T-cell products that improve response rates, reduce toxicity, facilitate use in more diverse malignancies including solid tumors, reduce production costs, and facilitate allogeneic CAR T-cell products.61 Forecasts project nearly 900 total registered trials in CAR T-cell therapy between 2020 and 2025.61 Clinical trials are underway evaluating the use in the first- and second-line settings.62-64 Autologous CAR T cells must be manufactured for specific patients and failure to manufacture autologous CAR T cells occurs in 1% to 13% of patients.14,19,21,65 This personalized medicine approach increases the cost and the time required to prepare, deliver, and administer CAR T-cell products, creating significant limitations for large-scale clinical applications. “Off-the-shelf”/ready-to-use therapeutic CAR T cells from an allogeneic donor source offer the potential for large-scale clinical applications and avoidance of patient delays.61 Natural killer cells engineered to express a CAR have also shown activity in early-phase trials.66


The field of CAR T-cell therapy is evolving rapidly, with 2 new therapies approved by the FDA in the first 6 months of 2021 and a total of 5 products in the past 5 years. While all CAR T-cell products are currently approved in the third- or later-line setting, clinical trials in the first- and second-line setting are underway. Use of CAR T-cell therapy in the second-line setting outside of clinical trials has been observed.67 All of the studies of CAR T-cell products have been single-arm, phase 1 or 2 studies with no comparison arm; however, markedly improved response rates, PFS, and OS compared with historical data have been observed. The cost of CAR T-cell therapy is estimated between $373,000 and $475,000 per infusion, not including patient care costs (eg, evaluation, apheresis, chemotherapy, and post-infusion care, including management of complications).2 Given the number of new products entering the market and significant cost burden of therapies, managed care professionals should have an understanding of the clinical trial data, toxicity profile, and place in therapy in lymphoma, myeloma, and ALL, as well as guideline recommendations for adverse effect management associated with CAR T-cell therapies.

Author affiliation: Larry W. Buie, PharmD, BCOP, FASHP, is manager, Clinical Pharmacy, and program director, PGY2 Oncology Residency, Memorial Sloan Kettering Cancer Center, New York, NY.

Funding source: This activity is supported by educational grants from Bristol Myers Squibb; Kite Pharma, Inc; and Novartis Pharmaceuticals Corporation.

Author disclosure: Dr Buie has no relevant financial relationships with commercial interests to disclose.

Authorship information: Concept and design, analysis and interpretation of data, critical revision of the manuscript for important intellectual content.

Address correspondence to:

Medical writing and editorial support provided by: Julianna Merten, PharmD, BCPS, BCOP


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