2L PILOT trial

A Phase 2, open-label, single-arm trial (N=61)1

PILOT trial: First and only CAR T cell therapy pivotal trial to exclusively enroll second-line LBCL patients who were transplant-ineligible1

Primary endpoint: ORR1
Select secondary endpoints: CR rate, DOR, EFS, PFS, and OS1
Patients were required to meet ≥1 criteria that, per physician discretion, deemed them transplant-ineligible.1
Bridging therapy prior to receiving Breyanzi® was optional.1
Breyanzi provided unprecedented efficacy in transplant-ineligible patients regardless of time to relapse1
Response rates in the PILOT trial (N=61)1*
Graphic depicting response rates in PILOT trial
Graphic depicting response rates in PILOT trial
The median duration of study follow-up was 11.2 months.1
* Per the Lugano criteria, as assessed by an IRC.
† Two-sided 95% exact Clopper-Pearson confidence intervals.
The first and only CAR T cell therapy in 2L LBCL studied in transplant-ineligible patients1
Duration of response in
the PILOT trial1
Number of responders‡ 49/61
DOR§
Median (months) 11.2
(95% CI) 5.1, NR
Range 0.0+ to 22.8+
DOR if best overall response is CR
Median (months) NR
(95% CI) 11.2, NR
Range 2.0+ to 22.8+
DOR if best overall response is PR
Median (months) 2.10
(95% CI) 1.4, 2.3
Range 0.0+ to 7.9+
Of the patients who achieved a CR, 83% had remission lasting at 6 months and 68% had remission lasting at 12 months.**
In responders who experienced a best overall response of CR, DOR was not yet reached1
CAR, chimeric antigen receptor; CI, confidence interval; CR, complete response; DOR, duration of response; EFS, event-fee survival; IRC, independent review committee; LBCL, large B-cell lymphoma; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; NR; not reached.
‡ Per the Lugano criteria, as assessed by an IRC.
§ A + sign indicates a censored value.
Kaplan-Meier (KM) method is used to obtain 2-sided 95% confidence intervals.
** Kaplan-Meier estimate.
PILOT trial1:
Graphic depicting PILOT trial process
Graphic depicting PILOT trial process
  • Primary endpoint: ORR1
  • Select secondary endpoints: CR rate, DOR, EFS, PFS, OS1
PILOT trial design and patient disposition
Of 74 patients who underwent leukapheresis:
  • 61 (82%) received Breyanzi and comprise the main efficacy population
  • 1 (1.4%) received CAR-positive T cells that did not meet the product specifications for Breyanzi (manufacturing failure)
  • 12 (16%) did not receive CAR-positive T cells for other reasons
Patients were allowed to recieve bridging therapy prior to receiving Breyanzi. Bridging chemotherapy was permitted between leukapheresis and the start of lymphodepleting chemotherapy.1
33% of patients were treated in an outpatient setting per physicians’ discretion1
Select patient demographics1,3
Trial included primary refractory and relapse patients
Characteristics1,3 (N=61)
Age; range 74 years; 53-84 years
ECOG PS 0/1/2 at screening 30%/44%/26%
Primary refractory 53%
Relapsed 47%
LBCL subtypes
DLBCL, NOS 51%
High-grade B-cell lymphoma 33%
DLBCL transformed from follicular lymphoma 15%
CR, complete response; CY, cyclophosphamide; ECOG PS, Eastern Cooperative Oncology Group performance status; EFS, event-free survival; DOR, duration of response; DLBCL, diffuse large B-cell lymphoma; FLU, fludarabine; NOS, not otherwise specified; OS, overall survival; PET, positron emission tomography; PFS, progression-free survival.
PILOT: Survival endpoints2
Rates of survival in the PILOT trial2* Median months (95% CI)
PFS 9.03 (4.17, NR)†
EFS 7.23 (3.22, 22.6)‡
OS NR (17.28, NR)§
Breyanzi progression-free survival (PFS) was 9.03 months2* in patients who were transplant-ineligible.2
  • EFS, PFS, and OS were secondary endpoints in PILOT and were not statistically tested in the setting of a single-arm trial
Survival data are not in the USPI and should be interpreted with caution. The statistical significance of these outcomes is not known.
Overall survival was not yet reached at data cutoff
EFS, event-free survival; NR, not reached; OS, overall survival; PFS, progression-free survival.
* Kaplan-Meier (KM) method is used to obtain 2-sided 95% confidence intervals.
† Median follow-up: 13.0 months.
‡ Median follow-up: 16.4 months.
§ Median follow-up: 17.6 months.
Important Safety Information
LESS
Important Safety Information

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

  • Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
  • Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
  • BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
CYTOKINE RELEASE SYNDROME
Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Among patients receiving BREYANZI for LBCL (N=418), CRS occurred in 46% (190/418), including ≥ Grade 3 CRS (Lee grading system) in 3.1% of patients.
In patients receiving BREYANZI after two or more lines of therapy for LBCL, CRS occurred in 46% (122/268), including ≥ Grade 3 CRS in 4.1% of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 98% with a median duration of 5 days (range: 1 to 17 days).
In patients receiving BREYANZI after one line of therapy for LBCL, CRS occurred in 45% (68/150), including Grade 3 CRS in 1.3% of patients. The median time to onset was 4 days (range: 1 to 63 days). CRS resolved in all patients with a median duration of 4 days (range: 1 to 16 days).
The most common manifestations of CRS (≥10%) included fever (94%), hypotension (42%), tachycardia (28%), chills (23%), hypoxia (16%), and headache (12%).
Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).
Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI.
Of the 418 patients who received BREYANZI for LBCL, 23% received tocilizumab and/or a corticosteroid for CRS, including 10% who received tocilizumab only and 2.2% who received corticosteroids only.
NEUROLOGIC TOXICITIES
Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred.
In patients receiving BREYANZI after two or more lines of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 35% (95/268), including ≥ Grade 3 in 12% of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of neurotoxicity was 8 days (range: 1 to 46 days). Neurologic toxicities resolved in 85% with a median duration of 12 days (range: 1 to 87 days).
In patients receiving BREYANZI after one line of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 27% (41/150) of patients, including Grade 3 cases in 7% of patients. The median time to onset of neurologic toxicities was 8 days (range: 1 to 63 days). The median duration of neurologic toxicity was 6 days (range: 1 to 119 days).
In all patients combined receiving BREYANZI for LBCL, neurologic toxicities occurred in 33% (136/418), including ≥ Grade 3 cases in 10% of patients. The median time to onset was 8 days (range: 1 to 63), with 87% of cases developing by 16 days. Neurologic toxicities resolved in 85% of patients with a median duration of 11 days (range: 1 to 119 days). Of patients developing neurotoxicity, 77% (105/136) also developed CRS.
The most common neurologic toxicities (≥ 5%) included encephalopathy (20%), tremor (13%), aphasia (8%), headache (6%), dizziness (6%), and delirium (5%).
CRS AND NEUROLOGIC TOXICITIES MONITORING
Monitor patients daily for at least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time.
BREYANZI REMS
Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:
  • Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
  • Certified healthcare facilities must have on-site, immediate access to tocilizumab.
  • Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
  • Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com, or contact Bristol-Myers Squibb at 1-888-423-5436.
HYPERSENSITIVITY REACTIONS
Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).
SERIOUS INFECTIONS
Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion.
In patients receiving BREYANZI for LBCL, infections of any grade occurred in 36% with Grade 3 or higher infections occuring in 12% of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7%, bacterial infections occurred in 4.3%, viral infections in 1.9% and fungal infections in 0.5%.
Febrile neutropenia developed after BREYANZI infusion in 8% of patients with LBCL. Febrile neutropenia may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.
Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.
Avoid administration of BREYANZI in patients with clinically significant active systemic infections.
Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells.
In patients who received BREYANZI for LBCL, 15 of the 16 patients with a prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines.
PROLONGED CYTOPENIAS
Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion.
Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 36% of patients with LBCL and included thrombocytopenia in 28%, neutropenia in 21%, and anemia in 6%.
Monitor complete blood counts prior to and after BREYANZI administration.
HYPOGAMMAGLOBULINEMIA
B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI.
In patients receiving BREYANZI for LBCL, hypogammaglobulinemia was reported as an adverse reaction in 11% of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 28% of patients.
Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.
Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.
SECONDARY MALIGNANCIES
Patients treated with BREYANZI may develop secondary malignancies. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for developing altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks.
ADVERSE REACTIONS
The most common nonlaboratory adverse reactions (incidence ≥ 30%) are fever, CRS, fatigue, musculoskeletal pain, and nausea.
The most common Grade 3-4 laboratory abnormalities (≥ 30%) include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Indication
BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:
  • refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or
  • refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or
  • relapsed or refractory disease after two or more lines of systemic therapy.
Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma.
References
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V5.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed July 7, 2023. To view the most recent and complete version of the guideline, go online to NCCN.org.
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  2. Kamdar M, Solomon S, Arnason J, et al. Lisocabtagene maraleucel, a CD19-directed chimeric antigen receptor T cell therapy, versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma: results from the randomized phase 3 TRANSFORM study. Presented at the 63rd American Society of Hematology Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA.
  3. Data on file. BMS-REF-LIS-0016. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  4. Kamdar M, Solomon S, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from the randomized phase 3 interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294-2308.
  5. Abramson J, Solomon S, Arnason J, et al. Lisocabtagene maraleucel (liso-cel) versus standard of care (SOC) with salvage chemotherapy followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients with relapsed or refractory large B-cell lymphoma (LBCL): primary analysis of the randomized, phase 3 transform study. Presented at the 64th American Society of Hematology Annual Meeting & Exposition; December 10-13, 2022; New Orleans, Louisiana.
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  2. Sehgal A, Hoda D, Riedell P, et al. Lisocabtagene maraleucel as a second-line therapy for relapsed or refractory large B-cell lymphoma in patients not intended for hematopoietic stem cell transplantation: primary analysis from the phase 2 PILOT study. Presented at the American Society of Oncology Annual Meeting; June 3-7, 2022; Chicago, IL.
  3. Data on file. BMS-REF-LIS-0019. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  2. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396(10254):839-852.
  3. Data on file. TRANSCEND DOR. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  4. Abramson J, Palomba M, Gordon L, et al. Two-year follow-up of TRANSCEND NHL 001, a multicenter phase 1 study of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphomas. Presented at the 63rd American Society of Hematology Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA.
  5. Data on file. TRANSCEND CD19. Princeton, NJ: Bristol-Myers Squibb Company; 2022.
  1. Breyanzi [package insert]. Summit, NJ: Bristol-Myers Squibb Company; 2023.
  2. Kamdar M, Solomon S, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294-2308.
  3. Abramson J, Palomba M, Gordon L, et al. Two-year follow-up of TRANSCEND NHL 001, a multicenter phase 1 study of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphomas. Presented at the 63rd American Society of Hematology Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA.

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