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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 1/2020

01-01-2020 | Non-Hodgkin Lymphoma | Review Article

Clinical Pharmacokinetic and Pharmacodynamic Considerations in Treating Non-Hodgkin Lymphoma

Authors: Nikki Blosser, Jennifer Jupp, Patrick Yau, Douglas Stewart

Published in: Clinical Pharmacokinetics | Issue 1/2020

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Abstract

Non-Hodgkin lymphoma (NHL) includes a variety of closely related malignancies that originate from lymphoid precursors. The majority of NHLs are of B-cell lineage, for which traditional therapy involves chemotherapy in combination with the anti-CD20 monoclonal antibody rituximab. Ongoing research into the pathogenesis of NHL subtypes has given rise to the use of novel agents that target specific molecular pathways. While the incidence of NHL extends over a range of ages from pediatric to elderly settings, the majority of diagnoses occur over age 60 years. Increasing the use of concomitant medication coupled with declining organ function among this group of patients creates pharmacokinetic (PK) challenges in administering a number of agents involved in the treatment of NHL. In addition, since many of the new agents are administered orally, there are a number of added PK factors that must be taken into consideration with their prescribing and administration. This article will review the available literature on the PK and pharmacodynamic properties of agents commonly used in the treatment of NHL, and intends to provide information that can assist with properly using these drugs in this setting.
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Literature
1.
2.
Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med. 1993;328:1002–6.PubMed
3.
Pferundschuh M, Trumper L, Kloess M, Schmits R, Feller AC, Rudolph C, et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood. 2004;104:626–33.
4.
Leoni L. Bendamustine: rescue of an effective antineoplastic agent from the mid-twentieth century. Semin Hematol. 2011;48:S4–11.PubMed
5.
Garattini S. Pharmacokinetics in cancer chemotherapy. Eur J Cancer. 2007;43:271–82.PubMed
6.
Moore M. Clinical pharmacokinetics of cyclophosphamide. Clin Pharmcokinet. 1991;20(3):194–208.
7.
8.
9.
Aapro MS, Walko CM. Aprepitant: drug-drug interactions in perspective. Ann Oncol. 2010;21(12):2316–23.PubMed
10.
de Jonge ME, Huitema AD, Holtkamp MJ, van Dam SM, Beijnen JH, Rodenhuis S. Aprepitant inhibits cyclophosphamide bioactivation and thiotepa metabolism. Cancer Chemother Pharmacol. 2005;56(4):370–8.PubMed
11.
Bubalo JS, Leis JF, Curtin PT, et al. A randomized, double-blinded, pilot trial of aprepitant added to standard antiemetics during conditioning therapy for hematopoietic stem cell transplant (HSCT). J Clin Oncol. 2007;25:9112.
12.
13.
Johnson SA, Richardson DS. Anthracyclines in hematology: pharmacokinetics and clinical studies. Blood Rev. 1998;12:52–71.PubMed
14.
Perez-Blanco JS, Santos-Buelga D, Ferandez deGatta MM, Herandez-Rivas JM, Martin A, Garcia MJ. Population pharmacokinetics of doxorubicin and doxorubicinol in patients diagnosed with non-Hodgkin’s lymphoma. Br J Clin Pharmacol. 2016;82(6):1517–27.PubMedPubMedCentral
15.
16.
Zamorano JL, Lancellotti P, Munoz DR, Aboyans V, Asteggiano R, Galderisi M, et al. 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of ESC Committee for Practice Guidelines. Eur Heart J. 2016;36:2768–801.
17.
18.
Pizzo P, Poplack D. Principles and practice of pediatric oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.
19.
Said R, Tsimberidou A. Pharmacokinetic evaluation of vincristine for the treatment of lymphoid malignancies. Expert Opin Drug Metab Toxicol. 2014;10(3):483–94.PubMed
20.
Egelhakin A, Ferguson MJ, MacGill E, Lehmann AS, et al. Increased risk of vincristine neurotoxicity associated with low CYP3A5 expression genotype in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2011;56(3):361–7.
21.
Krochinsky FP, Friedrichsen K, Mueller J, Haenel M, Ehninger G, Schleyer E. Oral etoposide is equivalent to intravenous administration within the CHOEP-Regimen—results of a comparative pharmacokinetic study. Blood. 2006;108:4662.
22.
23.
24.
Rummel M, Gregory S. Bendamustine’s emerging role in the management of lymphoid malignancies. Semin Hematol. 2011;48:S24–6.PubMed
25.
Elefante A, Czuczman MS. Bendamustine for the treatment of indolent non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Am J Health Syst Pharm. 2010;67(9):713–23.PubMed
26.
Leoni L, Lorenzo M, Hartley J. Mechanism of action: the unique pattern of bendamustine-induced cytotoxicity. Semin Hematol. 2011;48:S12–23.PubMed
27.
28.
Niitsu N. Non-Hodgkin’s lymphoma in the elderly: a guide to drug treatment. Drugs Aging. 1999;14(6):447–57.PubMed
29.
Wasil T, Licthman SM. Clinical pharmacology issues relevant to the dosing and toxicity of chemotherapy drugs in the elderly. Oncologist. 2005;10(8):602–12.PubMed
30.
Griggs JJ, Mangu PB, Anderson H, Balaban EP, Dignam JJ, Hryniuk WM, et al. Appropriate chemotherapy dosing for obese adult patients with cancer. J Clin Oncol. 2012;30:1553–61.PubMed
31.
Hanley MJ, Abernethy DR, Greenblatt DJ. Effect of obesity on the pharmacokinetics of drugs in humans. Clin Pharmacokinet. 2010;49:71–87.PubMed
32.
Han PY, Duffull SV, Kirkpatrick CM, Green B. Dosing in obesity: a simple solution to a big problem. Clin Pharmacol Ther. 2007;82:505–8.PubMed
33.
34.
Manches O, Lui G, Chaperot L, et al. In vitro mechanisms of action of rituximab on primary non-Hodgkin lymphomas. Blood. 2003;101:949–54.PubMed
35.
36.
Koene HR, Kleijer M, Algra J, Roos D, von dem Borne AE, de Haas M. Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Blood. 1997;90:1109–14.PubMed
37.
Dall’Ozzo S, Tartas S, Paintaud G, et al. Rituximab-dependent cytotoxicity by natural killer cells: influence of FCGR3A polymorphism on the concentration-effect relationship. Cancer Res. 2004;64:4664–9.PubMed
38.
Wu J, Edberg JC, Redecha PB, et al. A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. J Clin Investig. 1997;100:1059–70.PubMedPubMedCentral
39.
Kim DH, Jung HD, Kim JG, et al. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Blood. 2006;108:2720–5.PubMed
40.
Cartron G, Dacheux L, Salles G, et al. Therapeutic activity of humanizedanti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood. 2002;99:754–8.PubMed
41.
Gota V, Karanam A, Rath S, et al. Population pharmacokinetics of Reditux™, a biosimilar Rituximab, in diffuse large B-cell lymphoma. Cancer Chemother Pharmacol. 2016;78(2):353–9.PubMed
42.
Coiffier B. Pharmacokinetics, efficacy and safety of the rituximab biosimilar CT-P10. Expert Rev Clin Pharmacol. 2017;10(9):923–33.PubMed
43.
44.
McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825–33.PubMed
45.
Jager U, Fridrik M, Zeitlinger M, Heintel D, Hopfinger G, Burgstaller S, et al. Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. Haematologica. 2012;97:1431–8.PubMedPubMedCentral
46.
Muller C, Murawski N, Wiesen MH, Held G, Poeschel V, Zeynalova S, et al. The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood. 2012;119:3276–84.PubMed
47.
Golay J, Semenzato G, Rambaldi A, Foa R, Gaidano G, Gamba E, et al. Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics. MAbs. 2013;5:826–37.PubMedPubMedCentral
48.
Sawalha Y, Smith MR. Rituximab dosing in B cell lymphoma. Sci Proc. 2016;3:e1463.
49.
Cartron G, Blasco H, Paintaud G, Watier H, Le Guellec C. Pharmacokinetics of rituximab and its clinical use: thought for the best use? Crit Rev Oncol Hematol. 2007;62:43–52.PubMed
50.
Berinstein NL, Grillo-Lopez AJ, White CA, Bence-Bruckler I, Maloney D, Czuczman M, et al. Association of serum Rituximab (IDEC-C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin’s lymphoma. Ann Oncol. 1998;9:995–1001.PubMed
51.
Gordan LN, Grow WB, Pusateri A, Douglas V, Mendenhall NP, Lynch JW. Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders. J Clin Oncol. 2005;23:1096–102.PubMed
52.
Kahl BS, Williams ME, Hong F, Gascoyne R, Horning SJ. Preliminary Pharmacokinetic (PK) Analysis of Eastern Cooperative Oncology Group Protocol E4402: Rituximab Extended Schedule or Re-Treatment Trial (RESORT). Blood. 2007;110:3420.
53.
Salles G, Seymour JF, Offner F, Lopez-Guillermo A, Belada D, Xerri L, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011;377:42–51.PubMed
54.
Pfreundschuh M, Müller C, Zeynalova S, et al. Suboptimal dosing of rituximab in male and female patients with DLBCL. Blood. 2014;123(5):640–6.PubMed
55.
Murawski N, Pfreundschuh M, Zeynalova S, Poeschel V, Hanel M, Held G, et al. Optimization of rituximab for the treatment of DLBCL (I): dose-dense rituximab in the DENSE-R-CHOP-14 trial of the DSHNHL. Ann Oncol. 2014;25:1800–6.PubMed
56.
Pfreundschuh M, Poeschel V, Zeynalova S, Hanel M, Held G, Schmitz N, et al. Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the german high-grade non-Hodgkin lymphoma study group. J Clin Oncol. 2014;32:4127–33.PubMed
57.
Pfreundschuh M, Murawski N, Zeynalova S, et al. Optimization of rituximab for the treatment of DLBCL: increasing the dose for elderly male patients. Br J Haematol. 2017;179(3):410–20.PubMed
58.
Daydé D, Ternant D, Ohresser M, et al. Tumor burden influences exposure and response to rituximab:pharmacokinetic-pharmacodynamic modeling using a syngeneic bioluminescent murine model expressing human CD20. Blood. 2009;113:3765–72.PubMed
59.
Tout M, Casasnovas O, Meignan M, et al. Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report. Blood. 2017;129(19):2616–23.PubMed
60.
Davies Andrew, Merli Francesco, Mihaljevic Biljana, et al. Pharmacokinetics and safety of subcutaneous rituximab in follicular lymphoma (SABRINA): stage 1 analysis of a randomised phase 3 study. Lancet Oncol. 2014;15:343–52.PubMed
61.
Davies A, Merli F, Mihaljević B, et al. Efficacy and safety of subcutaneous rituximab versus intravenous rituximab for first-line treatment of follicular lymphoma (SABRINA): a randomised, open-label, phase 3 trial. Lancet Haematol. 2017;4(6):e272–82.PubMed
62.
Lugtenburg P, Avivi I, Berenschot H, et al. Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study. Haematologica. 2017;102(11):1913–22.PubMedPubMedCentral
63.
Rummel M, Kim TM, Aversa F, et al. Preference for subcutaneous or intravenous administration of rituximab among patients with untreated CD20 + diffuse large B-cell lymphoma or follicular lymphoma: results from a prospective, randomized, open-label, crossover study (PrefMab). Ann Oncol. 2017;28(4):836–42.PubMed
64.
Said R, Tsimberidou AM. Obinutuzumab for the treatment of chronic lymphocytic leukemia and Other B-cell lymphoproliferative disorders. Expert Opin Biol Ther. 2017;17(11):1463–70.PubMedPubMedCentral
65.
Liu SD, Chalouni C, Young JC, et al. Afucosylated antibodies increase activation of FcgammaRIIIa-dependent signaling components to intensify processes promoting ADCC. Cancer Immunol Res. 2015;3(2):173–83.PubMed
66.
Herter S, Herting F, Mundigl O, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013;12(10):2031–42.PubMed
67.
Cartron G, Hourcade-Potelleret F, Morschhauser F. Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma. Haematologica. 2016;101(2):226–34.PubMedPubMedCentral
68.
Gibiansky E, Gibiansky L, Carlile DJ, et al. Population pharmacokinetics of obinutuzumab (GA101) in chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma and exposure-response in CLL. CPT Pharmacometr Syst Pharmacol. 2014;3:e144.
69.
Goede VFK, Bosch F, Follows G, et al. Updated survival analysis from the CLL11 Study: obinutuzumab versus rituximab in chemoimmunotherapy-treated patients with chronic lymphocytic leukemia. Blood. 2015;126:1733.
70.
Vitolo U, Trněný M, Belada D, et al. Obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated diffuse large B-cell lymphoma. J Clin Oncol. 2017;35(31):3529–37.PubMed
71.
Marcus RE, Davies A, Ando K, et al. Obinutuzumab-based induction and maintenance prolongs progression-free survival in patients with previously untreated follicular lymphoma: primary results of the randomized phase 3 GALLIUM study [abstract no. 6]. American Society of Hematology Annual Meeting; 3–6 Dec 2016: San Diego, CA.
72.
Cheson BD, Chua N, Mayer J, et al. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN Study. J Clin Oncol. 2018;36(22):2259–66.PubMed
73.
Advani R, Buggy J, Sharman J, et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013;31(1):88–94.PubMed
74.
Dreyling M, Jurczak W, Jerkeman M, Silva RS, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016;387(10020):770–8.PubMed
75.
Küppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer. 2005;5(4):251–62.PubMed
76.
Wang ML, Rule S, Martin P, Goy A, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369(6):5017.
77.
Buggy JJ, Elias L. Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. Int Rev Immunol. 2012;31(2):119–32.PubMed
78.
Marostica E, Sukbuntherng J, Loury D, et al. Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. Cancer Chemother Pharmacol. 2015;75(1):111–21.PubMed
79.
80.
de Vries R, Smit J, Hellemans P, et al. Stable isotope-labelled intravenous microdose for absolute bioavailability and effect of grapefruit juice on ibrutinib in healthy adults. Br J Clin Pharmacol. 2015;81(2):235–45.
81.
de Jong J, Sukbuntherng J, Skee D, et al. The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia. Cancer Chemother Pharmacol. 2015;75(5):907–16.PubMedPubMedCentral
82.
de Jong J, Skee D, Hellemans P, et al. Single-dose pharmacokinetics of ibrutinib in subjects with varying degrees of hepatic impairment. Leuk Lymphoma. 2017;58(1):185–94.PubMed
83.
de Jong J, Skee D, Murphy J. Effect of CYP3A perpetrators on ibrutinib exposure in healthy participants. Pharmacol Res Perspect. 2015;3(4):1–11.
84.
de Jong J, Hellemans P, De Wilde S, Patricia D, et al. A drug–drug interaction study of ibrutinib with moderate/strong CYP3A inhibitors in patients with B-cell malignancies. Leuk Lymphoma. 2018;59(12):2888–95.PubMed
85.
De Zwart L, Snoeys J, De Jong J, Sunkbuntherng J, Mannaert E, Monshouwer M. Ibrutinib dosing strategies based on interaction potential of CYP3A4 perpetrators using physiologically based pharmacokinetic modeling. Clin Pharmacol Ther. 2016;100(5):548–57.PubMed
86.
O’Brien S, Hillmen P, Coutre S, Barr PM, et al. Safety analysis of four randomized controlled studies of ibrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma or mantle cell lymphoma. Clin Lymphoma Myeloma Leuk. 2018;18(10):648–57.PubMed
87.
Davies A. Idelalisib for relapsed/refractory indolent B-cell non-Hodgkin’s lymphoma: an overview of pharmacokinetics and clinical trial outcomes. Exp Rev Hematol. 2015;8(5):581–93.
88.
Flinn IW, Kahl BS, Leonard JP, et al. Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma. Blood. 2014;123(22):3406–13.PubMedPubMedCentral
89.
Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, et al. PI3 Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008–18.PubMedPubMedCentral
90.
Keating GM. Idelalisib: a review of its use in chronic lymphocytic leukaemia and indolent non-Hodgkin’s lymphoma. Target Oncol. 2015;10(1):141–51.PubMed
91.
Ramanathan S, Jin F, Sharma S, Kearney B. Clinical pharmacokinetic and pharmacodynamics profile of idelalisib. Clin Pharmacokinet. 2016;55(1):33–45.PubMed
92.
Feng J, Gao Y, Zhou H, Fang L, Li X, Ramanathan S. Population pharmacokinetic modeling of idelalisib, a novel PI3Kδ inhibitor, in healthy subjects and patients with hematologic malignancies. Cancer Chemother Pharmacol. 2016;77(1):89–98.
93.
Jin F, Robeson M, Zhou H, Moyer C, Ramanathan S. Pharmacokinetics and safety of idelalisib, a novel PI3Kδ inhibitor, in Japanese and Caucasian subjects. Blood. 2013;122(2):5575.
94.
Jin F, Robeson M, Zhou H, Kwan E, Ramanathan S. Pharmacokinetics, metabolism and excretion of idelalisib. Blood. 2013;122(21):5570.
95.
Jin F, Robeson M, Zhou H, Hisoire G, Ramanathan S. The pharmacokinetics and safety of idelalisib in subjects with moderate or severe hepatic impairment. J Clin Pharmacol. 2015;55(8):944–52.PubMed
96.
97.
Jin F, Robeson M, Zhou H, Hisoire G, Ramanathan S. The pharmacokinetics and safety of idelalisib in subjects with severe renal impairment. Cancer Chemother Pharmacol. 2015;76(6):1133–41.PubMed
98.
Webb HK, Chen H, Yu AS, et al. Clinical pharmacokinetics of CAL-101, a p110d isoform-selective PI3K inhibitor, following single- and multiple dose administration in healthy volunteers and patients with hematological malignancies. Blood. 2010;116(21):1774.
99.
Jin F, Robeson M, Zhou H, Moyer C, Wilbert S, Murray B, Ramanathan S. Clinical drug interaction profile of idelalisib in healthy subjects. J Clin Pharmacol. 2015;55(8):909–19.PubMed
100.
101.
Davids MS, Roberts AW, Seymour JF, Pagel JM, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017;35(8):826–33.PubMedPubMedCentral
102.
de Vos S, Swinnen LJ, Wang D, Reid E, et al. Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase 1b dose-finding study. Ann Oncol. 2018;29(9):1932–8.PubMedPubMedCentral
103.
Zinzani PL, Flinn IW, Yuen S, Topp MS, et al. Efficacy and safety of venetoclax (Ven) + rituximab (R) or Ven + bendamustine (B) + R randomized versus B + R in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL): final analysis of phase II CONTRALTO Study. Blood. 2018;132:1614.
104.
Roberts AW, Davids MS, Pagel JM, Kahl BS, et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Eng J Med. 2016;374(4):311–22.
105.
Jones AK, Freise KJ, Agarwal SK, Humerickhouse RA, Wong SL, Salem AH. Clinical predictors of venetoclax pharmacokinetics in chronic lymphocytic leukemia and non-Hodgkin’s lymphoma patients: a pooled population pharmacokinetic analysis. AAPS J. 2016;18(5):1192–202.PubMed
106.
Salem AH, Agarwal SK, Dunbar M, Nuthalapati S, Chien D, Freise K, et al. Effect of low- and high-fat meals on the pharmacokinetics of venetoclax, a selective first-in-class BCL-2 inhibitor. J Clin Pharmacol. 2016;56(11):1355–61.PubMed
107.
108.
Agarwal SK, Hu B, Chien D, Wong S, Salem AH. Evaluation of rifampin’s transporter inhibitory and CYP3A inductive effects on the pharmacokinetics of venetoclax, a BCL-2 inhibitor: results of a single- and multiple-dose study. J Clin Pharmacol. 2016;56(11):1335–43.PubMed
109.
Liu H, Michmerhuizen MJ, Lao Y, Wan K, et al. Metabolism and disposition of a novel B-cell lymphoma-2 inhibitor venetoclax in humans and characterization of its unusual metabolites. Drug Metab Dispos. 2017;45(3):294–305.PubMed
110.
Agarwal SK, Salem AH, Danilov AV, Hu B, et al. Effect of ketoconazole, a strong CYP3A inhibitor, on the pharmacokinetics of venetoclax, a BCL-2 inhibitor, in patients with non-Hodgkin lymphoma. Br J Clin Pharmacol. 2017;83(4):846–54.PubMedPubMedCentral
111.
Freise KJ, Salem AH. Impact of ritonavir dose and schedule on CYP3A inhibition and venetoclax clinical pharmacokinetics. Eur J Clin Pharmacol. 2018;74(4):413–21.PubMed
112.
Chiney MS, Menon RM, Bueno OF, Tong B, Salem AH. Clinical evaluation of p-glycoprotein inhibition by venetoclax: a drug interaction study with digoxin. Xenobiotica. 2018;48(9):904–10.PubMed
113.
Salem AH, Hu B, Freise KH, Agarwal SK, Sidhu DS, Wong SL. Evaluation of the pharmacokinetic interaction between venetoclax, a selective BCL-2 inhibitor, and warfarin in healthy volunteers. Clin Drug Investig. 2017;37(3):303–9.PubMed
114.
115.
Goy A, Kalayoglu Besisik S, Drach J, et al. Longer-term follow-up and outcome by tumour cell proliferation rate (Ki-67) in patients with relapsed/refractory mantle cell lymphoma treated with lenalidomide on MCL-001 (EMERGE) pivotal trial. Br J Haematol. 2015;170(4):496–503.PubMedPubMedCentral
116.
Leonard J, et al. AUGMENT: a phase III randomized study of lenalidomide plus rituximab (R2) vs Rituximab/placebo in patient with relapsed/refractory indolent non-hodgkin lymphoma. ASH Annual Meeting 2018, Session 623; 30 Nov–4 Dec 2018: San Diego, CA.
117.
Morschhauser F, Fowler N, Feugier P, et al. Rituximab plus lenalidomide in advanced untreated follicular lymphoma. N Engl J Med. 2018;379(10):934–47.PubMed
118.
Nowakowski GS, Laplant B, Macon WR, et al. Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma: a phase II study. J Clin Oncol. 2015;33(3):251–7.PubMed
119.
Nowakowski GS, Chiapella A, et al. ROBUST: Lenalidomide-R-CHOP versus placebo-R-CHOP in previously untreated ABC-type diffuse large B-cell lymphoma. Future Oncol. 2016;12(13):1553–63.PubMedPubMedCentral
120.
Wang M, Fowler N, Wagner-Bartak N, et al. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013;27(9):1902–9.PubMed
121.
Kritharis A, Coyle M, Sharma J, Evens AM. Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities. Blood. 2015;125(16):2471–6.PubMedPubMedCentral
122.
Ramsay A, Clear A, Kelly G, et al. Follicular lymphoma cells induce T-cell immunologic synapse dysfunction that can be repaired with lenalidomide implications for the tumor microenvironment and immunotherapy. Blood. 2009;114:4713–20.PubMedPubMedCentral
123.
Hughes J, Phelps M, Upton R, et al. Population pharmacokinetics of lenalidomide in patients with B-Cell malignancies. Br J Clin Pharmacol. 2019;85(5):924–34.PubMedPubMedCentral
124.
Chen N, Zhou S, Palmisano M, et al. Clinical pharmacokinetics and pharmacodynamics of lenalidomide. Clin Pharamicokinet. 2017;56:139–52.
125.
Morita TO, Yamaguchi A, et al. Stability of lenalidomide suspension after preparation by a simple suspension method for enteral tube administration. J Oncol Pharm Prac. 2016;22(4):579–83.
126.
Rubenstein J, Geng H, Fraser E. Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma. Blood Adv. 2018;2(13):1595–606.PubMedPubMedCentral
127.
Chen N. Distribution of lenalidomide into semen of healthy men after multiple oral doses. J Clin Pharacol. 2010;50(7):767–74.
128.
129.
Adams J. The development of proteasome inhibitors as anticancer drugs. Cancer Cell. 2004;5(5):417–21.PubMed
130.
Fisher R, Berstein S, Kahl B, et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2006;24(30):4867–74.PubMed
131.
Friedberg JW, Vose JM, Kelly JL, Young F, et al. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood. 2011;117(10):2807–12.PubMedPubMedCentral
132.
Robak T, Jin J, Pylypenko H, Verhoef G, et al. Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study. Lancet Oncol. 2018;19(11):1449–58.PubMed
133.
Chen C, Kouroukis T, White D, Voralia M, Stadtmauer E, Stewart AK, et al. Bortezomib is active in patients with untreated or relapsed Waldenstrom’s macroglobulinemia: a phase II study of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007;25(12):1570–5.PubMed
134.
Treon S, Ioakimidis L, Soumerai JD, Patterson C, et al. Primary therapy of Waldenstrom macroglobulinemia with bortezomib, dexamethasone and rituximab: WMCTG clinical trial 05-180. J Clin Oncol. 2009;27(23):3830–5.PubMedPubMedCentral
135.
Leblond V, Kastritis E, Advani R, et al. Treatment recommendations from the Eighth International Workshop on Waldenstrom’s macroglobulinemia. Blood. 2016;128(10):1321–8.PubMed
136.
Tan C, Majeed S, Cael B, Barta S. Clinical pharmacokinetics and pharmacodynamics of bortezomib. Clin Pharmacokinet. 2019;50:157–68.
137.
Papandreou C, Daliani D, Nix D, Yang H, et al. Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. J Clin Oncol. 2004;22(11):2108–21.PubMed
138.
Schwartz R, Davidson T. Pharmacology, pharmacokinetics and practical applications of bortezomib. Oncology (Williston Park). 2004;18(14 Suppl. 11):14–21.PubMed
139.
Yuan T, Zhang F, Yao QM, Liu YX, Zhu XJ, Wang X. Weekly versus biweekly bortezomib given in patients with indolent non-Hodgkin lymphoma: a meta-analysis. PLoS One. 2017;12(5):e0177950.PubMedPubMedCentral
140.
Moreau P, Karamanesht II, Domnikova N, et al. Pharmacokinetic, pharmacodynamics and covariate analysis of subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma. Clin Pharamcokinet. 2012;51(12):823–9.
141.
Reece D, Sullivan D, Lonial S, Mohrbacher A, et al. Pharmacokinetic and pharmacodynamics study of two doses of bortezomib in patients with relapsed multiple myeloma. Cancer Chemother Pharmacol. 2011;67(1):57–67.PubMed
142.
Labutti J, Parsons I, Huang R, et al. Oxidative deboronation of the peptide boronic acid proteasome inhibitor bortezomib: contributions from reactive oxygen species in this novel cytochrome P450 reaction. Chem Res Toxicol. 2006;19(4):539–46.PubMed
143.
Uttamsignh V, Lu C, Miwa G, et al. Relative contributions of the five major human cytochromes P450, 1A2, 2C9, 2C19, 2D6, and 3A4, to the hepatic metabolism of the proteasome inhibitor bortezomib. Drug Metab Dispos. 2005;33(11):1723–8.
144.
Leal T, Remick S, Takimoto C, et al. Dose-escalating and pharmacological study of bortezomib in adult cancer patients with impaired renal function: a national Cancer Institute Organ Dysfunction Working Group Study. Cancer Chemother Pharmacol. 2011;68(6):1439–47.PubMedPubMedCentral
145.
LoRusso PM, Venkatakrishnan K, Ramanathan RK, Sarantopoulos J. Pharmacokinetics and safety of bortezomib in patients with advanced malignancies and varying degrees of liver dysfunction: Phase I NCI Organ Dysfunction Working Group Study NCI-6432. Clin Cancer Res. 2012;18(10):2954–63.PubMed
146.
Venkatakrishnan K, Rader M, Ramananthan R, et al. Effect of the CYP3A inhibitor ketoconazole on the pharmacokinetics and pharmacodynamics of bortezomib in patients with advance solid tumors: a prospective multicenter, open-label, randomized, two-way crossover drug–drug interaction study. Clin Ther. 2009;31(Part 2):2444–58.PubMed
147.
Hellman A, Rule S, Walewski J, et al. Effect of cytochrome P450 3A4 inducers on the pharmacokinetic, pharmacodynamics and safety profiles of bortezomib in patients with multiple myeloma or non-Hodgkin’s lymphoma. Clin Pharmacokinet. 2011;50(12):781–91.
148.
Quinn D, Nemunaitis J, Fuloria J, et al. Effect of the cytochrome P450 2C19 inhibitor omeprazole on the pharmacokinetics and safety profile of bortezomib in patients with advanced solid tumours, non-Hodgkin’s lymphoma or multiple myeloma. Clin Pharmacokinet. 2009;48(3):199–209.PubMed
149.
Smith SM, Pitcher BN, Jung SH, et al. Safety and tolerability of idelalisib, lenalidomide, and rituximab in relapsed and refractory lymphoma: the Alliance for Clinical Trials in Oncology A051201 and A051202 phase 1 trials. Lancet Haematol. 2017;4(4):e176–82.PubMedPubMedCentral
Metadata
Title
Clinical Pharmacokinetic and Pharmacodynamic Considerations in Treating Non-Hodgkin Lymphoma
Authors
Nikki Blosser
Jennifer Jupp
Patrick Yau
Douglas Stewart
Publication date
01-01-2020
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 1/2020
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-019-00807-8

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