Axicabtagene Ciloleucel (Yescarta)

Number: 0924

Policy

Note: REQUIRES PRECERTIFICATION

Precertification of axicabtagene ciloleucel is required of all Aetna participating providers and members in applicable plan designs.  For precertification of axicabtagene ciloleucel, call 1-877-212-8811.

Aetna considers axicabtagene ciloleucel (Yescarta) medically necessary for the treatment of B-cell lymphomas in members 18 years of age or older when all of the following criteria are met:

  • Member has any of the following B-cell lymphoma subtypes:

    • Diffuse large B-cell lymphoma (DLBCL) arising from follicular lymphoma (also known as follicular lymphoma with histologic transformation to DLBCL)
    • Diffuse large B-cell lymphoma
    • Primary mediastinal large B-cell lymphoma
    • High-grade B-cell lymphoma (high-grade B-cell lymphoma with translocations of MYC and BCL2 and/or BCL6 [double/triple hit lymphoma], high-grade B-cell lymphoma, NOS)
    • Acquired immunodeficiency syndrome (AIDS)-related diffuse large B-cell lymphoma
    • Human herpesvirus 8 (HHV8)-positive diffuse large B-cell lymphoma, NOS
    • Monomorphic post-transplant lymphoproliferative disorder (B-cell type)

  • The member does not have primary central nervous system lymphoma
  • The member has not received a previous treatment course of Yescarta or another CD19-directed chimeric antigen receptor (CAR) T-cell therapy
  • The B-cells must be CD19-positive as confirmed by testing or analysis
  • For diffuse large B-cell lymphoma arising from follicular lymphoma: member received prior treatment with two or more chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated
  • For all other B-cell lymphoma subtypes: member has partial response following second-line therapy OR the disease is in second relapse or greater.

Aetna considers repeat administration of axicabtagene ciloleucel experimental and investigational because the effectiveness of this approach has not been established.

Aetna considers axicabtagene ciloleucel experimental and investigational for the following indications (not an all-inclusive list) because its effectiveness for these indications has not been established

  • Acute lymphoblastic leukemia (ALL)
  • Burkitt lymphoma
  • Indolent non-Hodgkin lymphomas (NHL) (other than follicular lymphomas with histologic transformation to DLBCL)
  • Mantle cell lymphoma
  • Marginal zone lymphoma
  • Primary central nervous system (CNS) lymphoma
  • Solid tumors.

See also CPB 0799 - Tocilizumab (Actemra) and CPB 0920 - Tisagenlecleucel (Kymriah).

Dosing Recommendations

Yescarta is available as a cell suspension for infusion.

Yescarta comprises a suspension of 2 × 106 CAR-positive viable T cells/kg of body weight, with a maximum of 2 × 108 CAR-positive viable T cells in approximately 68 ml

Dosing is based on the number of CAR-positive viable T cells.

The target Yescarta dose is 2 × 106 CAR-positive viable T cells/kg body weight, with a maximum of 2 × 108 CAR-positive viable T cells.

Source: Prescribing Information. Axicabtagene ciloleucel (Yescarta). Kite Pharma, Inc. 2017.

Background

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL) in adults.  About 72,000 new cases of NHL are diagnosed in the US yearly, and DLBCL represents about 1/3 newly diagnosed cases.  Axicabtagene ciloleucel (formerly KTE-C19), a chimeric antigen receptor (CAR) T cell therapy, has been studied for use in adult patients with large B-cell lymphoma including DLBCL, primary mediastinal large B-cell lymphoma (PMBCL), high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.

Roberts and colleagues (2018) stated that the development of clinically functional CAR T cell therapy is the culmination of multiple advances over the past 30 years.  Axicabtagene ciloleucel is an anti-CD19 CAR T cell therapy in development for patients with refractory DLBCL, including transformed follicular lymphoma (TFL) and PMBCL.  Axicabtagene ciloleucel is manufactured from patients' own peripheral blood mononuclear cells (PBMC) during which T cells are engineered to express a CAR that re-directs them to recognize CD19-expressing cells.  Studies have reported the feasibility of manufacturing axicabtagene ciloleucel in a centralized facility for use in multi-center clinical trials and have demonstrated potent anti-tumor activity in patients with refractory DLBCL.  Main acute toxicities are neurologic events as well as cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells causing high fever and flu-like symptoms.  The authors concluded that axicabtagene ciloleucel holds promise for the treatment of patients with CD19-positive malignancies, including refractory DLBCL.

On October 18, 2017, the U.S. Food and Drug Administration (FDA) approved axicabtagene ciloleucel (Yescarta) for the treatment of adults with relapsed or refractory (r/r)large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL, PMBCL, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.  The safety and effectiveness of Yescarta were established in a multi-center clinical trial of 101 adults with r/r large B-cell lymphoma.  Yescarta is the 2nd gene therapy approved by the FDA and the first for certain types of non-Hodgkin lymphoma (NHL).  Moreover, Yescarta is not indicated for the treatment of patients with primary central nervous system (CNS) lymphoma.

Neelapu and co-workers (2017) stated that in a phase-I clinical trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 CAR T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.  In this multi-center, phase-II clinical trial, these researchers enrolled 111 patients with DLBCL, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy.  Patients received a target dose of 2×106 anti-CD19 CAR T cells/kg body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine.  The primary end-point was the rate of objective response (calculated as the combined rates of complete remission [CR] and partial remission [PR]); secondary end-points included overall survival, safety, and biomarker assessments.  Among the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99 %) and administered to 101 (91 %).  The objective response rate (ORR) was 82 %, and the CR rate was 54 %.  With a median follow-up of 15.4 months, 42 % of the patients continued to have a response, with 40 % continuing to have a CR.  The overall rate of survival at 18 months was 52 %.  The most common adverse events (AEs) of grade-3 or higher during treatment were neutropenia (in 78 % of the patients), anemia (in 43 %), and thrombocytopenia (in 38 %).  Grade-3 or higher CRS and neurologic events occurred in 13 % and 28 % of the patients, respectively; 3 of the patients died during treatment.  Higher CAR T-cell levels in blood were associated with response.  The authors concluded that in this multi-center study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the CRS, and neurologic events.

Sharma and colleagues (2018) noted that B-cell NHL are the most common hematological malignancies, which despite improvements in chemo-immunotherapy, carry a uniformly poor prognosis in the relapsed/refractory setting.  CD19 is an antigen expressed on the surface of most malignancies arising from the B cells, and adoptive transfer of anti-CD19 chimeric antigen receptor (CAR)-expressing T cells has been shown to be effective in treating these B-cell malignancies.  Axicabtagene ciloleucel (KTE-C19) is an autologous anti-CD19 CAR T-cell therapy that has shown high ORRs and a manageable safety profile in patients with relapsed or refractory B-cell malignancies who lack effective and curative therapeutic options.  Axi-cel is currently approved by the FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy including DLBCL, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma, and is also being evaluated in other B-cell malignancies in ongoing clinical trials. 

Jain and associates (2018) stated that adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment.  Axicabtagene ciloleucel was initially developed at the National Cancer Institute (NCI) and has recently been commercially approved by the FDA for relapsed or refractory aggressive NHL including DLBCL and its variants.  The ZUMA-1 phase-I and phase-II clinical trials formed the basis of the FDA approval of this product, and these investigators discussed the particulars of the clinical trials and the pharmacology of axi-cel.

The National Comprehensive Cancer Netowrk (NCCN) Drugs & Biologics Compendium (2018) included the following category 2A recommendations:

Treatment of histologic transformation to diffuse large B-cell lymphoma (DLBCL) in patients who have received

  • minimal or no chemotherapy prior to histologic transformation to DLBCL and have partial response, no response, relapsed, or progressive disease following chemoimmunotherapy for transformed disease (only after treatment with ≥2 chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated)
  • multiple lines of chemoimmunotherapy (not including axicabtagene ciloleucel or tisagenlecleucel) for indolent or transformed disease (only after treatment with ≥2 chemoimmunotherapy regimens which included at least one anthracycline or anthracenedione-based regimen, unless contraindicated)

Used for diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, or high-grade B-cell lymphomas with translocations of MYC and BCL2 and/or BCL6 (double/triple hit lymphoma) as

  • additional therapy for patients with intention to proceed to high-dose therapy who have partial response following second-line therapy for relapsed or refractory disease
  • treatment of disease in second relapse or greater (if axicabtagene ciloleucel or tisagenlecleucel not previously given)

Treatment for monomorphic PTLD (B-cell type) as

  • additional therapy for patients with intention to proceed to high-dose therapy who have partial response following second-line chemoimmunotherapy for relapsed or refractory disease
  • treatment of disease in second relapse or greater (if not previously given).

AIDS-Related B-Cell Lymphomas

National Comprehensive Cancer Network’s Drugs & Biologics Compendium (2018) list AIDS-related B-cell lymphomas as a recommended indication of axicabtagene ciloleucel:

Therapy for relapsed AIDS-related diffuse large B-cell lymphoma and HHV8-positive diffuse large B-cell lymphoma, not otherwise specific (NOS) as (Recommendation: 2A)

  • Additional therapy for patients with intention to proceed to high-dose therapy who have partial response, no response, or progressive disease following second-line therapy for relapsed or refractory disease
  • Treatment of disease in second relapse or greater (if not previously given).

The Prescribing Information of Yescarta described a single-arm, open-label, multi-center trial that examined the effectiveness of a single infusion of Yescarta in adults with relapsed or r/r aggressive B-cell NHL.  Eligible patients had refractory disease to the most recent therapy or relapse within 1 year after autologous hematopoietic stem cell transplantation (HSCT).  The study excluded patients with prior allogeneic HSCT, any history of CNS lymphoma, Eastern cooperative oncology group (ECOG) performance status of 2 or greater, absolute lymphocyte count of less than 100/μL, creatinine clearance less than 60 ml/min, hepatic transaminases more than 2.5 times the upper limit of normal, cardiac ejection fraction of less than 50 %, or active serious infection.  Following lympho-depleting chemotherapy, Yescarta was administered as a single intravenous infusion at a target dose of 2 × 106 CAR-positive viable T cells/kg (maximum permitted dose: 2 × 108 cells).  The lympho-depleting regimen consisted of intravenous (iv) cyclophosphamide 500 mg/m2 and iv fludarabine 30 mg/m2, both given on the 5th, 4th, and 3rd day prior to initiation of Yescarta.  Bridging chemotherapy between leukapheresis and lympho-depleting chemotherapy was not permitted.  All patients were hospitalized for Yescarta infusion and for a minimum of 7 days afterward.  Of 111 patients who underwent leukapheresis, 101 received Yescarta.  Of the patients treated, the median age was 58 years (range of 23 to 76), 67 % were men, and 89 % were white.  Most (76 %) had DLBCL, 16 % had TFL, and 8 % had PMBCL.  The median number of prior therapies was 3 (range of 1 to 10), 77 % of the patients had refractory disease to a 2nd or greater line of therapy, and 21 % had relapsed within 1 year of autologous HSCT; 1 out of 111 patients did not receive the product due to manufacturing failure; 9 other patients were not treated, primarily due to progressive disease or serious adverse reactions following leukapheresis.  The median time from leukapheresis to product delivery was 17 days (range of 14 to 51 days), and the median time from leukapheresis to infusion was 24 days (range of 16 to 73 days).  The median dose was 2.0 × 106 CAR-positive viable T cells/kg (range of 1.1 to 2.2 × 106 cells/kg).  Effectiveness was established on the basis of CR rate and duration of response (DOR), as determined by an independent review committee.  The median time to response was 0.9 months (range of 0.8 to 6.2 months).  Response durations were longer in patients who achieved CR, as compared to patients with a best response of PR.  Of the 52 patients (51.5 %) who achieved CR, 14 initially had stable disease (7 patients) or PR (7 patients), with a median time to improvement of 2.1 months (range of 1.6 to 5.3 months).  Treatment with Yescarta can result in severe side effects, which usually appear within the first 1 to 2 weeks, but some side effects may occur later.  The most common non-laboratory adverse reactions (incidence greater than or equal to 20 %) are: CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections-pathogen unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness, constipation, and cardiac arrhythmias.  The Prescribing Information of Yescarta carries a boxed warning for CRS and neurologic toxicities, which can be fatal or life-threatening. 

Axicabtagene ciloleucel is also being investigated for the treatment of acute lymphoblastic leukemia (ALL), follicular lymphoma, indolent NHL, mantle cell lymphoma, and marginal zone lymphoma (NLM, 2017).

Burkitt Lymphoma

National Comprehensive Cancer Network’s Drugs & Biologics Compendium (2019) does not list Burkitt lymphoma as a recommended indication of axicabtagene ciloleucel.

Follicular Lymphoma

National Comprehensive Cancer Network’s Drugs & Biologics Compendium (2019) lists follicular lymphoma (grade 1 to 2) as a recommended indication of axicabtagene ciloleucel (Category 2A).
Treatment of histologic transformation to DLBCL in patients who have received:

  • Minimal or no chemotherapy prior to histologic transformation to DLBCL and have partial response, no response, or progressive disease after treatment with greater than or equal to 2 chemoimmunotherapy regimens, which included at least 1 anthracycline or anthracenedione-based regimen, unless contraindicated
  • Multiple lines of prior therapies (not including axicabtagene ciloleucel or tisagenlecleucel) for indolent or transformed disease (only after treatment with greater than or equal to 2 chemoimmunotherapy regimens, which included at least 1 anthracycline or anthracenedione-based regimen, unless contraindicated)

Solid Tumors

Baybutt and colleagues (2019) noted that in 2017, the FDA approved the first 2 novel cellular immunotherapies using synthetic, engineered receptors known as CARs, tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), expressed by patient-derived T cells for the treatment of hematological malignancies expressing the B-cell surface antigen CD19 in both pediatric and adult patients.  This approval marked a major milestone in the use of antigen-directed "living drugs" for the treatment of relapsed or refractory blood cancers, and with these 2 approvals, there is increased impetus to expand not only the target antigens but also the tumor types that can be targeted.  These researchers discussed the challenges, advances, and novel approaches being used to implement CAR T-cell immunotherapy for the treatment of solid tumors.  The authors concluded that given the difficulty in treating solid tumors with CAR T cells, the success witnessed in CD19‐directed CAR T‐cell therapy may appear serendipitous.  There is potentially some truth to this because CAR T‐cell therapy to treat T‐cell acute lymphoblastic leukemia (T‐ALL) has not been developed concurrently with B‐cell ALL CAR T‐cell therapy, given the risk for fratricide when targeting T‐cell antigens expressed in not only T‐ALL cells but also in the CAR T cells themselves.  Experience with CD19‐directed CAR T‐cell therapy has encouraged the CAR T‐cell community to confront the problems associated with expanding this therapy to other tumor types.  In fact, in the case of T‐ALL, Cooper et al (2018) have created a CAR that targets the T‐cell antigen CD7 and, to avoid CAR T‐cell fratricide, have used CRISPR/Cas9 to delete CD7 in the CAR T cells.  The necessary strategies to create more effective CAR T‐cell therapies are being developed, and this review has outlined some of the approaches investigators are taking to enhance the efficacy of these cells both within CD19‐targeted therapy and beyond.  These researchers stated that although a one‐size‐fits‐all approach is ideal, and investigators are seeking a cytokine signaling pathway that is a panacea for the limitations of treating solid tumors and unleashing the full potential of CAR T cells, the reality is that each cancer is unique and will ultimately require unique approaches to effectively eradicate disease using CAR T cells.

Furthermore, National Comprehensive Cancer Network’s Drugs & Biologics Compendium (2019) does not list any solid tumor as a recommended indication of axicabtagene ciloleucel.

Radiation Therapy as a Bridging Strategy for CAR T Cell Therapy with Axicabtagene Ciloleucel in Diffuse Large B-Cell Lymphoma

Sim and colleagues (2019) stated that axicabtagene ciloleucel (axi-cel) is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory r/r-DLBCL.  Bridging therapy may be required for lymphoma control during the manufacturing interval between collection of autologous T cells and final CAR T product administration.  The optimal bridging therapy is not known and patients are often chemo-refractory.  These researchers presented a case series of patients receiving radiation as a bridge to axi-cel.  Between December 2017 and October 2018, a total of 12 patients were intended to receive bridging radiation before axi-cel.  The group was characterized by highly aggressive disease including 6 of 12 with "double hit" lymphoma and 6 of 12 with disease greater than or equal to 10 cm in diameter.  All patients received 2 to 4 Gy/fraction to a median dose of 20 Gy (range of 6 to 36.5 Gy).  Half of patients received either 30 Gy in 10 fractions or 20 Gy in 5 fractions; 7 patients received concurrent chemotherapy; 11 patients underwent axi-cel infusion and 1 did not.  Median follow-up was 3.3 months (range of 1.1 to 12.0 months).  No significant toxicities were identified during bridging radiation, and no patient experienced in-field progression of disease before axi-cel infusion.  One patient experienced abdominal pain, which resolved after dose reduction. Two patients had out-of-field progression of disease during the bridging period.  After axi-cel infusion, 3 of 11 patients (27 %) experienced severe CRS or neurotoxicity.  At 30 days, the ORR was 81.8 % (11 of 12 evaluable; 1 stable disease [SD], 1 out-of-field progression), with CR in 27 % (3 of 11).  At last follow-up, the best ORR was 81.8 %, with a CR attained in 45 % (5 of 11).  Lymphocyte counts decreased slightly in 10 of 12 patients during radiation (median of 0.25 k/uL).  The authors concluded that radiation (with or without concurrent chemotherapy) could be safely administered as a bridge to axi-cel in high-risk lymphoma.  Moreover, these researchers stated that caution should be taken if irradiation is started before apheresis, and lymphocyte counts should be monitored closely throughout.  They stated that future investigation is needed to optimize the use of bridging radiation before CAR T therapy.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :

Other CPT codes related to the CPB:

96413 - 96417 Chemotherapy administration

HCPCS codes covered if selection criteria are met::

Q2041 Axicabtagene Ciloleucel, up to 200 Million Autologous Anti-CD19 CAR T Cells, Including Leukapheresis And Dose Preparation Procedures, Per Infusion

ICD-10 codes covered if selection criteria are met:

B20 Human immunodeficiency virus [HIV] disease
C82.00 - C82.99 Follicular lymphoma
C83.30 - C83.39 Diffuse large B-cell lymphoma.
C85.20 - C85.29 Mediastinal (thymic) large B-cell lymphoma
C85.80 - C85.89 Other specified types of non-Hodgkin lymphoma

ICD-10 codes not covered if selection criteria are met:

C11.0 - C11.9 Malignant neoplasm of nasopharynx
C12 Malignant neoplasm of pyriform sinus
C13.0 - C13.9 Malignant neoplasm of hypopharynx
C14.0-C14.8 Malignant neoplasm of other and ill-defined sites in the lip, oral cavity and pharynx
C15.3 - C15.9 Malignant neoplasm of esophagus
C16.0 - C16.9 Malignant neoplasm of stomach
C17.0 - C17.9 Malignant neoplasm of small intestine
C18.0 - C18.9 Malignant neoplasm of colon
C19 - C21.8 Malignant neoplasm of rectosigmoid junction, rectum, anus and anal canal
C22.0 Liver cell carcinoma
C22.1 Intrahepatic bile duct carcinoma
C23 - C24.9 Malignant neoplasm of gall bladder and other and unspecified parts of biliary tract
C25.0 - C25.9 Malignant neoplasm of pancreas
C26.0 - C26.9 Malignant neoplasm of other and ill-defined digestive organs
C30.0 - C30.1 Malignant neoplasm of nasal cavity and middle ear
C31.0 - C31.9 Malignant neoplasm of accessory sinuses (paranasal)
C33 - C34.92 Malignant neoplasm trachea, bronchus, and lung
C37 Malignant neoplasm of thymus
C38.0 - C38.8 Malignant neoplasm of heart, mediastinum and pleura
C39.0 - C39.9 Malignant neoplasm of other and ill-defined sites in the respiratory system and intrathoracic organs
C40.00 - C40.92 Malignant neoplasm of bone and articular cartilage of limbs
C41.0 - C41.9 Malignant neoplasm of bone and articular cartilage of other and unspecified sites
C43.0 - C43.9 Malignant melanoma of skin
C44.00 - C44.201 Other and unspecified malignant neoplasm of skin
C46.1 Kaposi’s sarcoma of soft tissue
C47.0 - C47.9 Malignant neoplasm of peripheral nerves, autonomic nervous system, connective and soft tissue
C48.0 - C48.8 Malignant neoplasm of retroperitoneum and peritoneum
C49.0 - C49.9 Malignant neoplasm of other connective and soft tissue
C50.011 - C50.929 Malignant neoplasm of female and male breast
C51.0 - C51.9 Malignant neoplasm of vulva
C52 Malignant neoplasm of vagina
C53.0 - C53.9 Malignant neoplasm of cervix uteri
C54.0 - C54.9 Malignant neoplasm of corpus uteri
C55 Malignant neoplasm of uterus, part unspecified
C56.1 - C56.9 Malignant neoplasm of ovary
C57.00 - C57.02 Malignant neoplasm of fallopian tube
C58 Malignant neoplasm of placenta
C60.0 - C60.9 Malignant neoplasm of penis
C61 Malignant neoplasm of prostate
C62.00 - C62.92 Malignant neoplasm of testis
C63.00 - C63.9 Malignant neoplasm of other and unspecified male genital organs
C64.1 - C68.9 Malignant neoplasm of kidney and other and unspecified urinary organs
C69.00 - C69.92 Malignant neoplasm of eye and adnexa
C70.0 - C70.9 Malignant neoplasm of meninges
C71.0 - C71.9 Malignant neoplasm of brain
C72.0 - C72.9 Malignant neoplasm of spinal cord, cranial nerves and other parts of central nervous system
C73 Malignant neoplasm of thyroid gland
C7A.1 - C7A.8 Malignant poorly differentiated neuroendocrine tumors
C80.0 - C80.1 Malignant neoplasm without specification of site
C83.70 - C83.79 Burkitt lymphoma
D00.00 - D09.9 Carcinoma in situ

The above policy is based on the following references:

  1. U.S. Food and Drug Administration (FDA). FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. FDA News. Silver Spring, MD: FDA; October 18, 2017.
  2. Kite Pharma, Inc. Yescarta (axicabtagene ciloleucel) suspension for intravenous infusion. Prescribing Information. Santa Monica, CA: Kite Pharma; October 2017.
  3. U.S. National Library of Medicine (NLM). ClinicalTrials.gov. Axicabtagene ciloleucel / United States. Available at: https://clinicaltrials.gov/ct2/results?cond=&term=axicabtagene+ciloleucel+&cntry1=NA%3AUS&state1=&Search=Search. Accessed October 24, 2017.
  4. Roberts ZJ, Better M, Bot A, et al. Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk Lymphoma. 2018;59(8):1785-1796. 
  5. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544.
  6. Sharma P, King GT, Shinde SS, et al. Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas. Drugs Today (Barc). 2018;54(3):187-198.
  7. Jain MD, Bachmeier CA, Phuoc VH, Chavez JC. Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma. Ther Clin Risk Manag. 2018;14:1007-1017.
  8. National Comprehensive Cancer Network (NCCN). Axicabtagene ciloleucel. NCCN Drugs & Biologics Compendium. Fort Washington, PA: NCCN; 2018.
  9. Cooper ML, Choi J, Staser K, et al. An “off‐the‐shelf” fratricide‐resistant CAR‐T for the treatment of T cell hematologic malignancies. Leukemia. 2018;32(9):1970-1983.
  10. Whittington MD, McQueen RB, Ollendorf DA, et al. Long-term survival and cost-effectiveness associated with axicabtagene ciloleucel vs chemotherapy for treatment of B-cell lymphoma. JAMA Netw Open. 2019;2(2):e190035.
  11. National Comprehensive Cancer Network. Drugs & Biologics Compendium. Axicabtagene ciloleucel. 2019. NCCN: Fort Washington, PA.
  12. Baybutt TR, Flickinger JC Jr, Caparosa EM, Snook AE. Advances in chimeric antigen receptor T-cell therapies for solid tumors. Clin Pharmacol Ther. 2019;105(1):71-78.
  13. Sim AJ, Jain MD, Figura NB, et al. Radiation therapy as a bridging strategy for CAR T cell therapy with axicabtagene ciloleucel in diffuse large B-cell lymphoma. Int J Radiat Oncol Biol Phys. 2019 Jun 5 [Epub ahead of print].
  14. Yescarta [package insert]. Santa Monica, CA: Kite Pharma; October 2017.
  15. The NCCN Drugs & Biologics Compendium® © 2019 National Comprehensive Cancer Network, Inc. https://www.nccn.org. Accessed April 17, 2019.
  16. The NCCN Clinical Practice Guidelines in Oncology® B-Cell Lymphomas (Version 2.2019).© 2019 National Comprehensive Cancer Network, Inc. https://www.nccn.org. Accessed April 17, 2019.