HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to LUMOXITI Prescribing Information for complete information.
LUMOXITI (moxetumomab pasudotox-tdfk)
Approval date: September 13, 2018
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
LUMOXITI is used to treat adults with hairy cell leukemia (HCL) whose disease has come back or has not improved after at least two prior treatments.
Hairy cell leukemia is a rare, slow-growing cancer of the blood. The disease is called hairy cell leukemia because the leukemia cells look "hairy" when viewed under a microscope.
How is this drug used?
LUMOXITI is given by a healthcare provider directly into the bloodstream through a needle in the vein. This is known as an intravenous, or IV infusion. It takes about 30 minutes to receive an LUMOXITI infusion.
LUMOXITI is given on Days 1, 3, and 5 of each 28-day treatment cycle.
What are the benefits of this drug?
In the clinical trial, thirty percent (24 of 80) of patients with HCL achieved success (durable complete response). This means that blood counts that returned to normal values were maintained for more than 6 months.
What are the benefits of this drug (results of trials used to assess efficacy)?
Efficacy of LUMOXITY was established on durable complete response rate (CR), defined as hematologic remission (hemoglobin ≥ 11 g/dL, neutrophils ≥ 1500/mm3, and platelets ≥ 100,000/mm3 without transfusions or growth factor for at least 4 weeks) more than 180 days after blinded Independent Review Committee (IRC)-assessed CR.
The table below summarizes other efficacy results established based on Overall Response Rate (ORR), complete response rate (CR), and duration of response (DOR).
Table 2. Additional Efficacy Results in Patients with HCL
|Independent Review Committee (IRC) Assessed
|Overall Response Rate|
|Overall Response Rate* (%) [95% CI]||75 [64, 84]|
|Complete Response† (%) [95% CI]||41 [30, 53]|
|Partial Response‡ (%) [95% CI]||34 [24, 45]|
|Duration of Response|
|Median in months [range]||NR [0+ to 43+]|
|Duration of CR|
|Median in months [range]||NR [0+ to 40+]|
CI=Confidence Interval; NR=Not Reached; + indicates censored observations
* ORR defined as best overall response of CR or PR.
† CR defined as clearing of the bone marrow of hairy cells by routine Hematoxylin & Eosin stain, radiologic resolution of pre-existing lymphadenopathy and/or organomegaly, and hematologic remission.
‡ PR defined as ≥ 50% decrease or normalization (< 500/mm3)="" in="" peripheral="" blood="" lymphocyte="" count,="" reduction="" of="" pre-existing="" lymphadenopathy="" and/or="" organomegaly,="" and="" hematologic="">
LUMOXITI Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: LUMOXITI worked similarly in men and women.
- Race: Most of the patients were White. Differences in how well the drug worked among races could not be determined because of the small number of patients in other races.
- Age: LUMOXITI worked better in patients younger than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The table below summarizes efficacy results by demographic subgroups. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.
Figure 4. Subgroup Analyses of Durable Complete Response
Adapted from FDA review
What are the possible side effects?
LUMOXITI may cause serious side effects including life threatening conditions called capillary leak syndrome and hemolytic uremic syndrome. Other serious side effects are kidney damage, infusion-related reactions and electrolyte abnormalities.
The most common side effects of LUMOXITI are infusion related reactions, body swelling, nausea, fatigue, headache, fever, constipation, anemia, and diarrhea.
What are the possible side effects (results of trials used to assess safety)?
The tables below summarize adverse reactions and laboratory abnormalities in patients with HCL who were treated with at least one dose of LUMOXITI in the trial.
Table 3. Adverse Reactions Reported in ≥20% (All Grades) of Patients with Hairy Cell Leukemia (HCL) Treated with LUMOXITI
|All Grades (%)||Grade 3 (%)|
|General Disorders and Administration Site Conditions|
|Injury, Poisoning, and Procedural Complications|
|Infusion related reactions‡||50||3.8|
|Nervous System Disorders|
|Blood and Lymphatic System Disorders|
*Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
‡Infusion related reactions: includes patients who were reported to have one or more infusion event that may be infusion-related on the day of study drug infusion.
LUMOXITI Prescribing Information
Table 4: Laboratory Abnormalities* in ≥ 20% (All Grades) Reported in Patients with HCL
|All Grades (%)||Grade 3 (%)||Grade 4 (%)|
|Neutrophil count decreased||41||11||20|
|Platelet count decreased||21||11||3.8|
|Blood Bilirubin increased||30||1.3||-|
|Alkaline phosphatase increased||20||-||-|
ALT=alanine aminotransferase; AST=aspartate aminotransferase; GGT=gamma glutamyl transferase
*Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and based on laboratory measurements worsening from baseline
LUMOXITI Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in men and women.
- Race: Most of the patients were White. Differences in the occurrence of side effects among races could not be determined because of the small number of patients in other races.
- Age: The occurrence of kidney side effects was higher in patients older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The tables below summarize treatment-emergent adverse events (TEAEs) by sex and age subgroups. Because of the small sample sizes, these exploratory analyses should be interpreted with caution.
Table 5. Subgroup Analyses of Adverse Events by Sex
|Any TEAE||62 (98.4)||17 (100)|
|Any grade 3 or 4||41 (65.1)||13 (76.5)|
|Serious AEs||18 (28.6)||10 (58.8)|
Table 6. Subgroup Analyses of Adverse Events by Age
|Any TEAE||48 (98.0)||31 (100)|
|Any grade 3 or 4||33 (67.3)||21 (67.7)|
|Serious AEs||17 (34.7)||11 (35.5)|
|Renal Toxicity*||5 (10.2)||10 (32.3)|
*includes acute kidney injury, blood creatinine increased, protein urine present, proteinuria, renal failure, renal impairment, urine output decreased
Clinical Trial Report
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved LUMOXITI based on evidence from one clinical trial (NCT 01829711) that was conducted in the United States, and Europe. Patients who participated in the trial had hairy cell leukemia and have received at least two prior treatments for their disease.
Figure 1 summarizes how many men and women were in the trial.
Figure 1. Baseline Demographics by Sex
Figure 2 and Table 1 below summarize by race patients who participated in the trial.
Figure 2. Baseline Demographics by Race
Table 1. Baseline Demographics by Race
|Race||Number of Patients||Percentage|
|Black or African American||1||1|
Figure 3 summarizes by age group patients who participated in the trial.
Figure 3. Baseline Demographics by Age
Who participated in the trials?
The table below summarizes demographics of all patients that participated in the trial.
Table 7. Baseline Demographics of Patients
N = 80
|Sex, n (%)|
|Race, n (%)|
|Black or African American||1 (1.3)|
|Native Hawaiian or Pacific Islander||0|
|Min, Max||34, 84|
|Age Group, n (%)|
|>=65 years||31 (38.8)|
|Ethnicity, n (%)|
|Hispanic or Latino||5 (6.3)|
|Non-Hispanic or Latino||67 (83.8)|
|Geographic Region, n (%)|
How were the trials designed?
There was one trial that evaluated the benefit and side effects of LUMOXITI in patients with hairy cell leukemia whose disease has come back or has not improved after two previous treatments.
Patients received LUMOXITI infusion on Days 1, 8, and 15 of a 28-day treatment cycle. Treatment continued for a maximum of 6 cycles or until disease progression or unacceptable side effects.
The benefit of LUMOXITI was evaluated by measuring how many patients achieved success called durable complete response. That meant that after the therapy was completed blood cell counts increased to normal values and remained at that level for 6 months without any transfusions or additional medicines for at least 4 weeks.
How were the trials designed?
The safety and efficacy of LUMOXITI were established in an open label, single-arm, multicenter trial in adult patients with relapsed or refractory hairy cell leukemia. Enrolled patients had histologically confirmed HCL or HCL variant with a need for therapy based on presence of cytopenias or splenomegaly and had received prior treatment with at least 2 systemic therapies, including a purine nucleoside analog (PNA).
Patients received LUMOXITI administered as a 30-minutes intravenous infusion on Days 1, 8, and 15 of a 28-day treatment cycle for a maximum of 6 cycles or until documentation of complete response (CR), disease progression, or unacceptable toxicity.
Efficacy of LUMOXITI in HCL was evaluated by the independent review committee (IRC)-assessed rate of durable CR, as confirmed by maintenance of hematologic remission (hemoglobin ≥ 11 g/dL, neutrophils ≥ 1500/mm3, and platelets ≥ 100,000/mm3 without transfusions or growth factor for at least 4 weeks) more than 180 days after IRC-assessed CR.
Additional efficacy outcome measures included overall response rate (ORR), CR, and duration of response.
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.