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A Real-world Study of the Effectiveness of Tisagenlecleucel in Acute Lymphoblastic Leukemia Patients

Completed
Conditions
Acute Lymphoblastic Leukemia
Registration Number
NCT07039383
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

This was a retrospective, cross-sectional, center-based chart review study that collected real-world data for relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) patients receiving tisagenlecleucel (tisa-cel). Five centers in the United States were included for the study.

The date of the initial tisa-cel infusion was defined as the index date. A baseline period from ALL diagnosis to the index date was used to capture patient characteristics including demographics, and disease and treatment history. The study period, defined as the period from tisa-cel infusion to the end of follow-up date, i.e. the last contact date on medical charts or death, whichever was earlier, was used to capture the clinical outcomes of tisa-cel among ALL patients.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
79
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Remission RateMonth 1 and Month 3

Remission rate was defined as the best overall response as either complete remission (CR) or complete remission with incomplete blood count recovery (CRi) to tisa-cel.

CR: \<5% blasts in bone marrow based on morphologic assessment, no evidence of extramedullary disease, full recovery of peripheral blood counts (platelets \> 100x10\^9/L, absolute neutrophil \> 1.0x10\^9/L, and circulating blasts \<1%), and blood transfusions independency (i.e., no transfusion or transfusion ≤7 days).

CRi: \<5% blasts in bone marrow, no evidence of extramedullary disease, but without full recovery of peripheral blood counts with or without blood transfusions independency.

Secondary Outcome Measures
NameTimeMethod
Demgraphics: WeightBaseline
Time From Tisa-cel Infusion to Subsequent AlloSCTBaseline up to approximately 3 years
Number of Patients per Demographic CategoryBaseline

Demographic categories included:

* Age group

* Gender

* Race

* Ethnicity

* Geographical region

* Distance between residence and referral center (\<5, 5-30, 30-60, \>60 miles)

* Type of insurance

Number of Patients by Disease Characteristics CategoryBaseline

Disease characteristics categories included:

* Relapse or refractory status before tisa-cel infusion

* CD19 tumor expression among relapsed patients before tisa-cel infusion

* Karnofsky or Lansky performance score (PS)

* Lymphoblast proportion in bone marrow (\<5%, \>= 5%)

* Conditions of interest before tisa-cel infusion

* Patients with relapse before tisa-cel infusion

* Number and type of relapse before tisa-cel infusion (any bone marrow and/or central nervous system relapse)

* Cytogenic testing performed at tisa-cel infusion

* Cytogenic abnormalities at tisa-cel infusion

* Number of distinct cytogenic abnormalities (1, 2, 3, 4+)

* Comorbidities at tisa-cel infusion

* Remission status at time of tisa-cel infusion

The Karnofsky and Lansky PS are measures of functional impairment. They run from 0 to 100, where 0 is death and 100 is normal health. The Karnofsky scale is for patients aged 16 years or older. The Lansky scale is for patients younger than 16 years old.

Number of Patients by Treatment Characteristics CategoryBaseline

Treatment characteristic categories included:

* Treatments of interest before tisa-cel infusion

* Number of prior lines of treatment category (1 to 7)

* Received prior allogenic stem cell transplant (alloSCT)

* Number of alloSCT received (0, 1, 2)

* Year of initial tisa-cel infusion

* Bridging treatment agent received before tisa-cel infusion

* Lymphodepleting regimen received before tisa-cel infusion

* Type of tisa-cel infusion dose received (single, multiple)

* Weight at tisa-cel infusion (\<= 50 kilograms \[kg\], \>50 kg)

Lymphoblast Proportion in Bone Marrow Before Tisa-cel InfusionBaseline
ALL Disease Duration at Tisa-cel InfusionBaseline
Time From Initial Diagnosis to First RelapseFrom initial diagnosis up to first tisa-cel infusion, approximately 13 years
Number of Patients by Time From Initial Diagnosis to First RelapseBaseline

Time intervals: \<18 months, 18-36 months, and \>36 months.

Time From Most Recent Relapse to Initial Tisa-cel InfusionFrom initial diagnosis up to first tisa-cel infusion, approximately 13 years
Number of Lines of Treatment Prior to Tisa-cel InfusionBaseline
Time From Tisa-cel Infusion to Loss of Follow-up or Death due to Any CauseBaseline up to approximately 3 years
Time From Leukapheresis to Tisa-cel InfusionFrom initial diagnosis up to first tisa-cel infusion, approximately 13 years
Time from Tisa-cel Infusion to B-cell AplasiaBaseline up to approximately 3 years
Number of Doses for Initial Tisa-cel InfusionBaseline

Number of doses for initial infusion was measured among those who received multiple doses.

Weight Adjusted Transduced Cell Dose Infused in Patients Who Weighed 50 kg or Less at Tisa-cel InfusionBaseline
Total Cell Dose Infused in Patients Who Weighed More Than 50 kg at Tisa-cel InfusionBaseline
Number of Patients by Conditions Experienced After Tisa-cel InfusionBaseline up to approximately 3 years
Number of Patients by Bone Marrow Minimal Residual Disease (MRD) StatusMonth 1 and Month 3

Bone marrow MRD is a measure of the number of cancer cells remaining in the body after treatment. The number of patients overall with bone marrow MRD negative and those who achieved CR or CRi response with bone marrow MRD negative after tisa-cel infusion was measured. Bone marrow MRD negative was based on clinical assessment by the investigator.

CR: \<5% blasts in bone marrow based on morphologic assessment, no evidence of extramedullary disease, full recovery of peripheral blood counts (platelets \> 100x10\^9/L, absolute neutrophil \> 1.0x10\^9/L, and circulating blasts \<1%), and blood transfusions independency (i.e., no transfusion or transfusion ≤7 days).

CRi: \<5% blasts in bone marrow, no evidence of extramedullary disease, but without full recovery of peripheral blood count with or without blood transfusions independency.

Duration of Remission (DOR)Months 1, 6, 12, 18, 24, and 30

DOR was defined as the time from onset of remission to relapse or death due to ALL.

Relapse was defined as:

* Reappearance of blasts in the blood (≥1%), or

* Reappearance of blasts in bone marrow (≥5%), or

* Appearance of any extramedullary disease

Relapse-free Survival (RFS)Months 1, 6, 12, 18, 24, and 30

RFS was defined as the time from onset of remission to relapse or death due to any cause.

Relapse was defined as:

* Reappearance of blasts in the blood (≥1%), or

* Reappearance of blasts in bone marrow (≥5%), or

* Appearance of any extramedullary disease

Event-free Survival (EFS)Months 1, 6, 12, 18, 24, and 30

EFS was defined as the time from tisa-cel infusion to the earliest of the following events: death due to any cause, relapse, treatment failure (i.e., no response), or new anticancer therapy for ALL (i.e., treatments other than tisa-cel or SCT).

Relapse was defined as:

* Reappearance of blasts in the blood (≥1%), or

* Reappearance of blasts in bone marrow (≥5%), or

* Appearance of any extramedullary disease

Overall Survival (OS)Months 1, 6, 12, 18, 24, and 30

OS was defined as the time from tisa-cel infusion to the date of death due to any cause.

Number of Patients who had AlloSCT After Tisa-cel InfusionUp to approximately 3 years

Patient counts were categorized by:

* Pre-planned/not pre-planned at time of tisa-cel infusion

* Achieved/had not achieved B-cell recovery at time of alloSCT

* Unknown B-cell recovery status

* Did not have B-cell aplasia

* alloSCT received within 12 months after tisa-cel infusion

* Relapse status after tisa-cel infusion before alloSCT

Number of Patients by Tisa-cel Reinfusion Received After Initial InfusionUp to approximately 3 years

Patient counts were categorized by:

* Received/did not receive reinfusion

* Received infusion within 12 months after initial infusion

* Reason for reinfusion

Time From Initial Tisa-cel Infusion to Tisa-cel ReinfusionBaseline up to approximately 3 years
Number of Patients by Type of new Anticancer Therapy (Other Than AlloSCT or Reinfusion) Received After Tisa-cel infusionUp to approximately 3 years
Number of Patients by B-cell Aplasia Status After Tisa-cel InfusionUp to approximately 3 years

B-cell aplasia status included:

* Experienced B-cell aplasia

* Recovered from B-cell aplasia

Number of Patients by use of Immunoglobulin (Ig) Replacement Therapy Among Those who Experienced B-cell AplasiaUp to approximately 3 years

Ig replacement therapy use was categorized as follows:

* Received Ig replacement therapy

* Received intravenous immunoglobulin (IVIG) therapy

* Ongoing IVIG therapy

* Stopped IVIG therapy

* Received subcutaneous immunoglobulin (SCIG) therapy

* Ongoing SCIG therapy

* B-cell aplasia recovered

Average Dose of Ig Replacement TherapyUp to approximately 3 years

Ig replacement therapy included IVIG and SCIG.

Duration of Ig Replacement TherapyUp to approximately 3 years

Ig replacement therapy included IVIG and SCIG.

Rate of Maintenance of B-cell AplasiaMonths 1, 2, 3, 6, 9, 12, 18, 24, 30
Number of Patients by Hospitalizations at Initial Tisa-cel InfusionBaseline

Hospitalization categories included not hospitalized, hospitalized for Tisa-cel infusion, and subsequently admitted to intensive care unit (ICU).

Length of Stay in Hospital for Initial Tisa-cel InfusionUp to approximately 3 years
Number of Patients by Hospitalizations After Tisa-cel InfusionUp to approximately 3 years

Hospitalization categories included hospitalized, not hospitalized, and first hospitalization.

Number of Hospitalizations After Tisa-cel InfusionUp to approximately 3 years
Length of Stay in Hospital After Tisa-cel InfusionUp to approximately 3 years
Time From Initial Tisa-cel Infusion to the First HospitalizationBaseline up to approximately 3 years
Number of Patients by Primary Reason for the First HospitalizationUp to approximately 3 years
Number of Patients by ICU Admissions After Tisa-cel InfusionUp to approximately 3 years

ICU admission categories included admitted to ICU, not admitted to ICU, and first ICU admission.

Number of ICU Admissions After Tisa-cel InfusionUp to approximately 3 years
Length of Stay per ICU Admission After Tisa-cel InfusionUp to approximately 3 years
Number of Patients by Primary Reason for ICU Admission After Tisa-cel InfusionUp to approximately 3 years

Trial Locations

Locations (1)

Novartis

🇺🇸

East Hanover, New Jersey, United States

Novartis
🇺🇸East Hanover, New Jersey, United States
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