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UKONIQ is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen and adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.

These indications are approved under accelerated approval based on overall response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION
  • Infections: Serious, including fatal, infections occurred in patients treated with UKONIQ. Grade 3 or higher infections occurred in 10% of 335 patients, with fatal infections occurring in <1%. The most frequent Grade ≥3 infections included pneumonia, sepsis, and urinary tract infection. Provide prophylaxis for Pneumocystis jirovecii pneumonia (PJP) and consider prophylactic antivirals during treatment with UKONIQ to prevent CMV infection, including CMV reactivation. Monitor for any new or worsening signs and symptoms of infection, including suspected PJP or CMV, during treatment with UKONIQ. For Grade 3 or 4 infection, withhold UKONIQ until infection has resolved. Resume UKONIQ at the same or a reduced dose. Withhold UKONIQ in patients with suspected PJP of any grade and permanently discontinue in patients with confirmed PJP. For clinical CMV infection or viremia, withhold UKONIQ until infection or viremia resolves. If UKONIQ is resumed, administer the same or reduced dose and monitor patients for CMV reactivation by PCR or antigen test at least monthly.
  • Neutropenia: Serious neutropenia occurred in patients treated with UKONIQ. Grade 3 neutropenia developed in 9% of 335 patients and Grade 4 neutropenia developed in 9%. Monitor neutrophil counts at least every 2 weeks for the first 2 months of UKONIQ and at least weekly in patients with neutrophil count <1 x 109/L (Grade 3-4) neutropenia during treatment with UKONIQ. Consider supportive care as appropriate. Withhold, reduce dose, or discontinue UKONIQ depending on the severity and persistence of neutropenia.
  • Diarrhea or Non-Infectious Colitis: Serious diarrhea or non-infectious colitis occurred in patients treated with UKONIQ. Any grade diarrhea or colitis occurred in 53% of 335 patients and Grade 3 occurred in 9%. For patients with severe diarrhea (Grade 3, i.e., >6 stools per day over baseline) or abdominal pain, stool with mucus or blood, change in bowel habits, or peritoneal signs, withhold UKONIQ until resolved and provide supportive care with antidiarrheals or enteric acting steroids as appropriate. Upon resolution, resume UKONIQ at a reduced dose. For recurrent Grade 3 diarrhea or recurrent colitis of any grade, discontinue UKONIQ. Discontinue UKONIQ for life-threatening diarrhea or colitis.
  • Hepatotoxicity: Serious hepatotoxicity occurred in patients treated with UKONIQ. Grade 3 and 4 transaminase elevations (ALT and/or AST) occurred in 8% and <1%, respectively, in 335 patients. Monitor hepatic function at baseline and during treatment with UKONIQ. For ALT/AST greater than 5 to less than 20 times ULN, withhold UKONIQ until return to less than 3 times ULN, then resume at a reduced dose. For ALT/AST elevation greater than 20 times ULN, discontinue UKONIQ.
  • Severe Cutaneous Reactions: Severe cutaneous reactions, including a fatal case of exfoliative dermatitis, occurred in patients treated with UKONIQ. Grade 3 cutaneous reactions occurred in 2% of 335 patients and included exfoliative dermatitis, erythema, and rash (primarily maculo-papular). Monitor patients for new or worsening cutaneous reactions. Review all concomitant medications and discontinue any potentially contributing medications. Withhold UKONIQ for severe (Grade 3) cutaneous reactions until resolution. Monitor at least weekly until resolved. Upon resolution, resume UKONIQ at a reduced dose. Discontinue UKONIQ if severe cutaneous reaction does not improve, worsens, or recurs. Discontinue UKONIQ for life-threatening cutaneous reactions or SJS, TEN, or DRESS of any grade. Provide supportive care as appropriate.
  • Allergic Reactions Due to Inactive Ingredient FD&C Yellow No. 5: UKONIQ contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons, frequently in patients who also have aspirin hypersensitivity.
  • Embryo-fetal Toxicity: Based on findings in animals and its mechanism of action, UKONIQ can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males with female partners of reproductive potential to use effective contraception during treatment and for at least one month after the last dose.
  • Serious adverse reactions occurred in 18% of 221 patients who received UKONIQ. Serious adverse reactions that occurred in ≥2% of patients were diarrhea-colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%). Permanent discontinuation of UKONIQ due to an adverse reaction occurred in 14% of patients. Dose reductions of UKONIQ due to an adverse reaction occurred in 11% of patients. Dosage interruptions of UKONIQ due to an adverse reaction occurred in 43% of patients.
  • The most common adverse reactions (>15%), including laboratory abnormalities, in 221 patients who received UKONIQ were increased creatinine (79%), diarrhea-colitis (58%, 2%), fatigue (41%), nausea (38%), neutropenia (33%), ALT increase (33%), AST increase (32%), musculoskeletal pain (27%), anemia (27%), thrombocytopenia (26%), upper respiratory tract infection (21%), vomiting (21%), abdominal pain (19%), decreased appetite (19%), and rash (18%).
  • Lactation: Because of the potential for serious adverse reactions from umbralisib in the breastfed child, advise women not to breastfeed during treatment with UKONIQ and for at least one month after the last dose.

References: 1. UKONIQ [prescribing information]. New York, NY: TG Therapeutics; 2021. 2. Esposito A, et al. JAMA Oncol. 2019;5(9):1347-1354. 3. Knight ZA, et al. Cell. 2006;125(4):733-747. 4. Nylander S, et al. J Thromb Haemost. 2012;10(10):2127-2136. 5. Ortiz-Maldonado V, et al. Ther Adv Hematol. 2015;6(1):25-36. 6. Kaneda MM, et al. Nature. 2016;539(7629):437-442. 7. Ali AY, et al. Leukemia. 2018;32(9):1958-1969. 8. Curigliano G, et al. Drug Saf. 2019;42(2):247-262. 9. Durand CA, et al. J Immunol. 2009;183(9):5673-5684. 10. Burger JA, Chiorazzi N. Trends Immunol. 2013;34(12):592-601. 11. Dong S, et al. J Clin Invest. 2019;129(1):122-136. 12. MacDonald D, et al. Curr Oncol. 2016;23(6):407-417. 13. Sindel A, et al. Blood. 2018;132(1 suppl):4125. 14. Dienstmann R, et al. Mol Cancer Ther. 2014;13(5):1021-1031. 15. Maharaj K, et al. Blood Adv. 2020;4(13):3072-3084. 16. Deng C, et al. Blood. 2017;129(1):88-99.

INDICATIONS

UKONIQ is indicated for the treatment of adult patients with:

  • Relapsed or refractory marginal zone lymphoma (MZL) who have received at least 1 prior anti-CD20-based regimen
  • Relapsed or refractory follicular lymphoma (FL) who have received at least 3 prior lines of systemic therapy

These indications are approved under accelerated approval based on overall response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Please see full Prescribing Information.

OF THE 4 PI3K ISOFORMS, UKONIQ SELECTIVELY INHIBITS PI3K-DELTA1

PI3K isoform Tissue/cell expression Prominent function

alpha α

Broad distribution2

  • Plays a role in tumorigenesis2,3
  • Involved in insulin signaling and glucose metabolism2,3

beta β

Broad distribution2

  • Involved in platelet activation4
  • Plays a role in the development of thrombotic diseases4

gamma γ

T cells, macrophages, neutrophils5-7

  • Involved in the innate immune response, suppresses inflammation5,6

delta δ

B cells5,8

  • Involved in the activation, proliferation, and survival of B cells5,8,9
The delta isoform is highly expressed in normal and malignant B lymphocytes and plays an important role in cell proliferation, cell survival, and antibody production5,8,9
  • PI3K-DELTA IS CRITICAL FOR THE PATHOGENESIS OF B-CELL LYMPHOMA10,11
Activation of the PI3K/AKT/mTOR pathway is a common feature of MZL and FL that results in lymphoma cell growth12-14
  • UKONIQ ALSO INHIBITS CK1-EPSILON1

CK1-epsilon is an important component in the (canonical and noncanonical) Wnt/beta-catenin signaling pathway15

Inhibition of CK1-epsilon may have effects on T-cell function and survival15

Inhibition of CK1-epsilon blocks lymphoma cell proliferation by suppressing oncogenes like MYC16

indications

UKONIQ is indicated for the treatment of adult patients with:

  • Relapsed or refractory marginal zone lymphoma (MZL) who have received at least 1 prior anti-CD20-based regimen
  • Relapsed or refractory follicular lymphoma (FL) who have received at least 3 prior lines of systemic therapy

These indications are approved under accelerated approval based on overall response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.

important safety information

  • Infections: Serious, including fatal, infections occurred in patients treated with UKONIQ. Grade 3 or higher infections occurred in 10% of 335 patients, with fatal infections occurring in <1%. The most frequent Grade ≥3 infections included pneumonia, sepsis, and urinary tract infection. Provide prophylaxis for Pneumocystis jirovecii pneumonia (PJP) and consider prophylactic antivirals during treatment with UKONIQ to prevent CMV infection, including CMV reactivation. Monitor for any new or worsening signs and symptoms of infection, including suspected PJP or CMV, during treatment with UKONIQ. For Grade 3 or 4 infection, withhold UKONIQ until infection has resolved. Resume UKONIQ at the same or a reduced dose. Withhold UKONIQ in patients with suspected PJP of any grade and permanently discontinue in patients with confirmed PJP. For clinical CMV infection or viremia, withhold UKONIQ until infection or viremia resolves. If UKONIQ is resumed, administer the same or reduced dose and monitor patients for CMV reactivation by PCR or antigen test at least monthly.
  • Neutropenia: Serious neutropenia occurred in patients treated with UKONIQ. Grade 3 neutropenia developed in 9% of 335 patients and Grade 4 neutropenia developed in 9%. Monitor neutrophil counts at least every 2 weeks for the first 2 months of UKONIQ and at least weekly in patients with neutrophil count <1 x 109/L (Grade 3-4) neutropenia during treatment with UKONIQ. Consider supportive care as appropriate. Withhold, reduce dose, or discontinue UKONIQ depending on the severity and persistence of neutropenia.
  • Diarrhea or Non-Infectious Colitis: Serious diarrhea or non-infectious colitis occurred in patients treated with UKONIQ. Any grade diarrhea or colitis occurred in 53% of 335 patients and Grade 3 occurred in 9%. For patients with severe diarrhea (Grade 3, i.e., >6 stools per day over baseline) or abdominal pain, stool with mucus or blood, change in bowel habits, or peritoneal signs, withhold UKONIQ until resolved and provide supportive care with antidiarrheals or enteric acting steroids as appropriate. Upon resolution, resume UKONIQ at a reduced dose. For recurrent Grade 3 diarrhea or recurrent colitis of any grade, discontinue UKONIQ. Discontinue UKONIQ for life-threatening diarrhea or colitis.
  • Hepatotoxicity: Serious hepatotoxicity occurred in patients treated with UKONIQ. Grade 3 and 4 transaminase elevations (ALT and/or AST) occurred in 8% and <1%, respectively, in 335 patients. Monitor hepatic function at baseline and during treatment with UKONIQ. For ALT/AST greater than 5 to less than 20 times ULN, withhold UKONIQ until return to less than 3 times ULN, then resume at a reduced dose. For ALT/AST elevation greater than 20 times ULN, discontinue UKONIQ.
  • Severe Cutaneous Reactions: Severe cutaneous reactions, including a fatal case of exfoliative dermatitis, occurred in patients treated with UKONIQ. Grade 3 cutaneous reactions occurred in 2% of 335 patients and included exfoliative dermatitis, erythema, and rash (primarily maculo-papular). Monitor patients for new or worsening cutaneous reactions. Review all concomitant medications and discontinue any potentially contributing medications. Withhold UKONIQ for severe (Grade 3) cutaneous reactions until resolution. Monitor at least weekly until resolved. Upon resolution, resume UKONIQ at a reduced dose. Discontinue UKONIQ if severe cutaneous reaction does not improve, worsens, or recurs. Discontinue UKONIQ for life-threatening cutaneous reactions or SJS, TEN, or DRESS of any grade. Provide supportive care as appropriate.
  • Allergic Reactions Due to Inactive Ingredient FD&C Yellow No. 5: UKONIQ contains FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons, frequently in patients who also have aspirin hypersensitivity.
  • Embryo-fetal Toxicity: Based on findings in animals and its mechanism of action, UKONIQ can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males with female partners of reproductive potential to use effective contraception during treatment and for at least one month after the last dose.
  • Serious adverse reactions occurred in 18% of 221 patients who received UKONIQ. Serious adverse reactions that occurred in ≥2% of patients were diarrhea-colitis (4%), pneumonia (3%), sepsis (2%), and urinary tract infection (2%). Permanent discontinuation of UKONIQ due to an adverse reaction occurred in 14% of patients. Dose reductions of UKONIQ due to an adverse reaction occurred in 11% of patients. Dosage interruptions of UKONIQ due to an adverse reaction occurred in 43% of patients.
  • The most common adverse reactions (>15%), including laboratory abnormalities, in 221 patients who received UKONIQ were increased creatinine (79%), diarrhea-colitis (58%, 2%), fatigue (41%), nausea (38%), neutropenia (33%), ALT increase (33%), AST increase (32%), musculoskeletal pain (27%), anemia (27%), thrombocytopenia (26%), upper respiratory tract infection (21%), vomiting (21%), abdominal pain (19%), decreased appetite (19%), and rash (18%).
  • Lactation: Because of the potential for serious adverse reactions from umbralisib in the breastfed child, advise women not to breastfeed during treatment with UKONIQ and for at least one month after the last dose.
Please see full Prescribing Information.

References: 1. UKONIQ [prescribing information]. New York, NY: TG Therapeutics; 2021. 2. Esposito A, et al. JAMA Oncol. 2019;5(9):1347-1354. 3. Knight ZA, et al. Cell. 2006;125(4):733-747. 4. Nylander S, et al. J Thromb Haemost. 2012;10(10):2127-2136. 5. Ortiz-Maldonado V, et al. Ther Adv Hematol. 2015;6(1):25-36. 6. Kaneda MM, et al. Nature. 2016;539(7629):437-442. 7. Ali AY, et al. Leukemia. 2018;32(9):1958-1969. 8. Curigliano G, et al. Drug Saf. 2019;42(2):247-262. 9. Durand CA, et al. J Immunol. 2009;183(9):5673-5684. 10. Burger JA, Chiorazzi N. Trends Immunol. 2013;34(12):592-601. 11. Dong S, et al. J Clin Invest. 2019;129(1):122-136. 12. MacDonald D, et al. Curr Oncol. 2016;23(6):407-417. 13. Sindel A, et al. Blood. 2018;132(1 suppl):4125. 14. Dienstmann R, et al. Mol Cancer Ther. 2014;13(5):1021-1031. 15. Maharaj K, et al. Blood Adv. 2020;4(13):3072-3084. 16. Deng C, et al. Blood. 2017;129(1):88-99.

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