Copiktra

Duvelisib (duvelisib) instructions

Common name: duvelisib

Trade name: Copiktra

All names: duvelisib, duvelisib, duvelis ib, Copiktra

Indications:

1. Indicated for adults with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior treatments.

2. Applicable to adults with relapsed/refractory follicular lymphoma (FL) after at least 2 treatments.

Usage and dosage:

Orally administered 25 mg, twice a day, 28-day cycle, with or without food

Adverse reactions:

>10%:

Neutropenia< /p>

Diarrhea or colitis

Anemia

Neutropenia

Thrombocytopenia

Increased ALT (alanine aminotransferase)

Increased lipase

Increased AST (aspartate aminotransferase)< /p>

Decreased phosphate

Hyperkalemia

Hyponatremia

Increased amylase

Hypoalbuminemia

Lymphocytosis

Fire

Increased creatinine

Up Respiratory tract infection

Pneumonia

Skin rash

Increased alkaline phosphatase

Hypocalcemia

Fatigue

Diarrhea or colitis

Nausea

Cough

Lymphocytes Hypertension

Lower respiratory tract infection

Hypokalemia

Musculoskeletal pain

Abdominal pain

Vomiting

Decreased appetite

Difficulty breathing

Edema

Weight loss Mild

1-10%:

Hypokalemia

Hyponatremia

Increased ALT (alanine aminotransferase)

Increased amylase

Fatigue

Lower respiratory tract infection

Hyperkalemia Symptoms

Increased AST (aspartate aminotransferase)

Decreased phosphate

Difficulty breathing

Fatigue

Abdominal pain

Hypoproteinemia

Hypocalcemia

Increased creatinine

Cough

Musculoskeletal pain

Edema

Contraindications:

None

Precautions:

Severe, including fatal (4%), with an incidence of infection of 31%; The most common serious infections were pneumonia, sepsis, and lower respiratory tract infections; the median time to onset of any grade infection was 3 months, with 75% of cases occurring within 6 months.

CMV reactivation/infection and severe/fatal PJP occur in 1% of treated patients; consider prophylactic antiviral agents during treatment.

Treat infection before initiating treatment; advise patients to report any new or worsening signs and symptoms of infection.

Severe, including fatal (≤1%), skin reactions occurred in 5%; fatal cases included DRESS and TEN; the median time to onset of any grade skin reaction was 3 months, and the median event duration was 1 month; features presenting with severe events include pruritus, erythema, or maculopapular rash; less common features include exanthem, desquamation, erythroderma, skin exfoliation, keratinocyte necrosis, and papular rash.

Severe, including fatal (<1%), pneumonia with no apparent infectious cause occurred in 5%; median time to onset of any grade pneumonia was 4 months, with 75% of cases occurring within 9 months; median event duration was 1 month, with 75% of cases resolving by 2 months.

Grade 3 and 4 ALT and/or AST elevations were 8% and 2%, respectively; the median time to onset of any grade aminotransferase elevation was 2 months, and the median event duration was 1 month; monitor liver function during treatment.

The incidence of grade 3 or 4 neutropenia was 42%; the median time to onset of grade ≥3 neutropenia was 2 months, with 75% of cases occurring within 4 months; monitor neutrophil counts at least every 2 weeks for the first 2 months of treatment, and at least weekly for neutrophil counts <1 Gi/L (grades 3-4).

Based on findings in animals and its mechanism of action, fetal harm may occur when administered to pregnant women.

Storage:

Storage temperature is 20-25°C (68-77°F), with an allowed deviation of 15-30°C (59-86°F)

Mechanism of action:

Duvelisib is an inhibitor of PI3K, and its inhibitory activity mainly targets the PI3K-δ and PI3K-γ isoforms expressed in normal and malignant B cells. Duvelisib induces growth inhibition and reduced viability in cell lines derived from malignant B cells and primary CLL tumor cells, and it inhibits several key cell signaling pathways, including B cell receptor signaling and CXCR12-mediated chemotaxis of malignant B cells. Additionally, duvelisib inhibited CXCL12-induced T cell migration and M-CSF- and IL-4-driven M2 polarization of macrophages.

Safety and Efficacy:

The Phase 3 clinical trial, called DUO, enrolled patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma and used duvelisib as monotherapy.

The results showed that compared with the control group using ofatumumab, patients treated with duvelisib had a significantly longer progression-free survival (PFS) (median PFS in the treatment group: 13.3 months, median PFS in the control group: 9.9 months; HR=0.52; p<0.0001), and the risk of disease progression or death was reduced by 48%.