Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or . government site. cancer. With this study, we showed that the first step in investigating the complex clinical syndrome of NT associated with CAR-T cell therapies is the accurate grading, which can then be used to investigate further associations of NT and clinically relevant markers (eg, age, tumor burden).27,28. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Monitor Closely (1)isoniazid increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Serious - Use Alternative (1)palifermin increases toxicity of brentuximab vedotin by Other (see comment). Use Caution/Monitor. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Monitor Closely (1)siponimod and brentuximab vedotin both increase immunosuppressive effects; risk of infection. CTCAE Files - National Institutes of Health Monitor patients for adverse reactions. Avoid or Use Alternate Drug. Use Caution/Monitor. Solved a patient receiveing an initial brentuximab infusion - Chegg Brentuximab Vedotin - NCI - National Cancer Institute This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive P-gp substrates. lasmiditan increases levels of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. 0000000016 00000 n fosamprenavir increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 0000010614 00000 n Use Caution/Monitor. . provided study materials or patients; V.V.R. 3 c. 4 d. 2 Expert Answer 100% (1 rating) 1st step All steps Final answer Step 1/2 Brentuximab is an antibody drug which ta. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling. Use Caution/Monitor. 2013 Dec;14(13):1348-56. doi: 10.1016/S1470-2045(13)70501-1. For 29 regraded patients without CRS, 11 (37.9%) were graded the same across all 3 scales. is approved to treat: Brentuximab vedotin Immunosuppressive therapies (eg, irradiation, antimetabolites, alkylating agents, cytotoxic drugs, corticosteroids [greater than physiologic doses]) may reduce immune response to dengue vaccine. ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, raised ICP/cerebral edema) not attributable to any other cause. PDF ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS - European Medicines Agency 2021 Aug;8(8):e562-e571. Closely monitor for reduced effectiveness of medications that bind to the human neonatal Fc receptor. In addition, inpatient care, as mandated in the ZUMA-1 trial, may have allowed more opportunity to detect sensitive changes in low-grade ICANS, which may not be as clearly identifiable in the outpatient setting in which approximately 25% of CAR-T cell therapy infusions were performed in JULIET. Avoid or Use Alternate Drug. Brentuximab Vedotin Infusion Reaction Management: A Case Study 2015 Aug;8(4):403-12. doi: 10.1586/17474086.2015.1044432. - Febrile neutropenia - - ANC <1000/mm3 with a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >=38 degrees C (100.4 degrees F) for more than one hour Life-threatening consequences; urgent intervention indicated Death Definition: Novartis Pharmaceuticals Corporation Web site. The ASTCT grading scale for ICANS is similarly domain-based and uses a modified version of the CARTOX-10 screening tool, called the Immune Effector Cell-Associated Encephalopathy (ICE) score. Monitor Closely (1)encorafenib, brentuximab vedotin. Thirty minutes after onset, the chest pain was persistent, and oxygen saturations were normal. National Library of Medicine Avoid taking selinexor with other medications that may cause dizziness or confusion. Monitor Closely (1)saquinavir increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. voxelotor will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. National Cancer Institute Monitor patients for adverse reactions. Thus, as done in real-world practice, complex patient cases went through an adjudication discussion by the 4 experts, similar to a clinical tumor board, referring back to the source documents when necessary. https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9yZWZlcmVuY2UubWVkc2NhcGUuY29tL2RydWcvYWRjZXRyaXMtYnJlbnR1eGltYWItdmVkb3Rpbi05OTk2ODA=, View explanations for tiers and Among the subgroup of 64 patients with CRS by the Penn scale, the CTCAE, mCRES, and ASTCT systems identified a rate of grade 3 or higher NT of 17.2%, 15.7%, and 15.7%, respectively (Table 6). Use Caution/Monitor. Canada residents can call a provincial poison control center. It is anticipated that future studies will have prospective data collected using more specific ICANS grading and allowing more precise comparisons of clinical trial adverse events. NT by ASTCT criteria provided concordance for 66 patients, a lower grade for 2 patients, and a higher grade for no patients compared with the mCRES scale (Figure 1B). Frequently Asked Questions - National Cancer Institute Use Caution/Monitor. Use Caution/Monitor. Front Oncol. Table 4: Alanine aminotransferase increased toxicity grading criteria (NCI CTCAE v4.03) The grading criteria in table 4 is translated and stored in the reference dataset LBGRADE. Monitor Closely (1)rifapentine decreases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Toxicity grading for laboratory results began in 1999 with CTCAE version 2.0. Cancer Chemother Pharmacol. Use Caution/Monitor. . All material on this website is protected by copyright, Copyright 1994-2023 by WebMD LLC. official website and that any information you provide is encrypted Use Caution/Monitor. Bookshelf rifabutin decreases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Eur J Haematol. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications. doi: https://doi.org/10.1182/bloodadvances.2019001305. Monitor Closely (1)enzalutamide will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. Search for other works by this author on: Chimeric antigen receptor-T cell therapy: Practical considerations for implementation in Europe, CAR T cell immunotherapy for human cancer, Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial, Analysis of safety data from 2 multicenter trials of CTL019 in pediatric and young adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Delayed onset bleomycin-induced pneumonitis. Monitor patients for adverse reactions. Thirty minutes later, however, Ms. R developed tingling and numbness in her feet and tongue. This suggests that the CTCAE scale would pose difficulties in reliable clinician training outcomes as well as consistent global institutional implementation. th{U j06,`A & NW`c-D&2,s;H$2DD;IXDjzRirTz6>XjNHWa][+RpVR=} \ShV*IQ_O|YAiBXvlX5y,seqHi|@h(cg="b&XY"im|%{7s\fI5I5FMi^Zqickfk,;n+{!iv |z$85w~#e ritonavir increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Fexinidazole inhibits CYP3A4. Correspondence: Richard T. Maziarz, Adult Blood and Marrow Stem Cell Transplant & Cellular Therapy Program, Knight Cancer Institute, Oregon Health and Science University, Mail code: OC14HO, 3181 SW Sam Jackson Park Rd, Portland, OR 97239; e-mail: maziarzr@ohsu.edu. However, these therapies are associated with unique, but common, adverse events that must be identified and managed appropriately: cytokine release syndrome (CRS) and neurological toxicity (NT).3,10,14-18 NT after CAR-T cell therapy generally occurs after the onset of CRS, and higher grades of NT tend to occur concurrently with higher grades of CRS.10,19 Clinical features of CAR-T cell therapy-associated NT are numerous, and patients can experience events such as headache, dizziness, delirium, seizures, dysphasia, hallucinations, and impaired motor and language skills.1,3-5,8,10 This may be distressing to the patient and the patients family, but fortunately, NT and CRS generally resolve within days with standard supportive therapy such as corticosteroids. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. It may be graded according to CTCAE v5.0. (A) Frequency of CRS event grades by the Penn, Lee, and ASTCT grading scales (N = 111). Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministered. -. Monitor Closely (1)itraconazole increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Unauthorized use of these marks is strictly prohibited. Use Caution/Monitor. Monitor Closely (1)tucatinib will increase the level or effect of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. -. };wN:iyUFYg,Wyi^dgvBMu9L> {Ij{>i JS8Lk6P&adAQWEPN_aKe7+S|O[u/_>v~?W I}yr>T%D$D5fqYsms xp `sv@K4([MhT3O Cancers | Free Full-Text | Brentuximab-Induced Peripheral Neurotoxicity Monitor patients for adverse reactions. Otherwise, call a poison control center right away. Editorial assistance was provided by Marie Louise Edwards, Lei Yin, and Yichen Lu from Analysis Group, Inc., and was supported by Novartis Pharmaceuticals Corporation. Ten months after chemotherapy completion, she presented with new PET-avid adenopathy in the cervical and paratracheal regions, and a biopsy revealed recurrent Hodgkin lymphoma. endstream endobj 1187 0 obj <>/Metadata 39 0 R/OCProperties<>/Outlines 66 0 R/PageLabels 1182 0 R/PageLayout/OneColumn/Pages 1184 0 R/PieceInfo<>>>/StructTreeRoot 79 0 R/Type/Catalog>> endobj 1188 0 obj <>/Font<>/ProcSet[/PDF/Text]>>/Rotate 0/StructParents 0/Type/Page>> endobj 1189 0 obj <>stream 2005;66(1):p. 195. doi: 10.1016/j.urology.2005.01.038. Monitor or titrate P-gp substrate dose if coadministered. apalutamide will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or substitute another drug for these medications when possible. B., Zhang X., et al. lenacapavir will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. sotorasib will decrease the level or effect of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. Bookshelf Santa Monica, CA: Kite Pharma, Inc; 2019, Kymriah [package insert]. 0000001503 00000 n Monitor patients for adverse reactions. A patient with an ICE score of 0 may be classified as grade 3 ICANS if awake with global aphasia, but a patient with an ICE score of 0 may be classified grade 4 ICANS if unarousable. The first dose of brentuximab vedotin was administered without difficulty, at full dose (1.8 mg/kg) at a standard infusion time of 30 minutes. Use Caution/Monitor. Monitor Closely (2)elagolix will increase the level or effect of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. European journal of haematology. posaconazole increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor (1)anastrozole will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 0000001684 00000 n USES: Brentuximab is used to treat certain types of cancers (Hodgkin's lymphoma, systemic anaplastic large cell lymphoma, peripheral T-cell lymphoma, primary cutaneous anaplastic large cell lymphoma, CD30-expressing mycosis fungoides). J.E.S. Consult your doctor for more details. The CTCAE contain a grading scale for each adverse event term representing the severity of the event. The Lancet. HHS Vulnerability Disclosure, Help Use Caution/Monitor. In addition, the proportion of likely nonattributable events picked up by the CTCAE system, and included in the FDA label, in the JULIET trial is very high compared with the NT identified by mCRES and ASTCT criteria. (a) Computed tomography (CT) of the chest showing patchy, nodular ground glass opacities along a bronchovascular distribution throughout both lungs. Epub 2015 Mar 19. Use Caution/Monitor. 0000001178 00000 n Monitor patients for adverse reactions. Use Caution/Monitor. In arm B, ORR was 63.6% (7/11 patients), with 5 (45%) CR, 2 (18% . It is not a substitute for medical advice. received honoraria, membership on the board of directors or advisory committees, and research funding from Celgene; consultancy and honoraria from Dava Oncology; honoraria and research funding from Genentech; membership on the board of directors or advisory committees for Gilead; consultancy, honoraria, and research funding from Merck; honoraria, membership on the board of directors or advisory committees, and research funding from Novartis; and consultancy, honoraria, and membership on the board of directors or advisory committees for Nordic Nanovector. <>/ProcSet [/PDF /Text /ImageB /ImageC /ImageI]>>/Rotate 180/MediaBox[0 0 612 792]>> Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.This drug may make you dizzy. tecovirimat will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use Caution/Monitor. The medical experts reached independent agreement for 19/68 patients (27.9%) for the mCRES grading scale and 47/68 patients (69.1%) by ASTCT criteria. what you should tell your doctor before using this drug. Modify Therapy/Monitor Closely. BV-induced peripheral neurotoxicity (BVIN) is one of the greatest concerns for haematologists treating HL for several reasons. Abstract 254, Kite announces two-year data for Yescarta, Juno Therapeutics reports clinical hold on the JCAR015 phase II ROCKET trial [press release]. -, Bouchard Herv, Viskov Christian, Garcia-Echeverria Carlos. An official website of the United States government. Modify Therapy/Monitor Closely. 2016;2016:2359437. doi: 10.1155/2016/2359437. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. This medication is given in a hospital or clinic and will not be stored at home. Minor/Significance Unknown. CRS grade and use of anticytokine therapy or corticosteroids were also obtained. Limitations of this analysis include its retrospective nature and the consequent insufficient detail for full implementation of the CARTOX grading system (eg, the prospective part of the CARTOX-10 score questionnaire), thus requiring the grouping of grade 1/2 NT events together. Serious - Use Alternative (1)voxelotor will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. If long-term use of such medications is essential, consider discontinuing efgartigimod and using alternative therapies. Contraindicated. Monitor patients for adverse reactions. In the JULIET trial, NT was graded, per protocol, using CTCAE v4.03 criteria (Table 1). hRo0W#Jl$$*h$[RdI%vdL,4CxG6oJ[$:l5K#KY8hDQH0 I@GQp'93BnESJK\ _!kXh3h@J(E[ G[ltceZuaP,{KMq0q.Rz^I!5HKrI1ui]~;hzELj.QUP{~^M D}-*C\4OQ#&2w8cHmQKQ+dp~WWI7OB=G''G'ap}(\;U;D_B^':o/oMjgRlr+rv#1}4s YXNTFIASyCm*5 ~}JW y./cA L6 Avoid or Use Alternate Drug. Monitor patients for adverse reactions. For example, if an event could not be reconciled by the 4 experts and was graded as 2, 3, 3, and 4, then grade 4 was the final grading. Antibody-drug conjugatesa new wave of cancer drugs. Regrade of JULIET trial patient-level data showed 50 patients as having any-grade NT by CTCAE, 19 patients by mCRES, and 19 patients by ASTCT criteria. Avoid taking selinexor with other medications that may cause dizziness or confusion. . This scale was then grouped with gradation of signs of increased intracranial pressure and presence of seizures, whereby the greatest level of toxicity in any given domain would also be captured as the overall CRES grade. Monitor Closely (1)tipranavir increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Monitor Closely (1)brentuximab vedotin decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. c_MGq|,`Y8vyD;L}v~@$\OpW2[[ZnFp4`q`/&MbzDBJ:*Y!0J-Xy>VYp{ iAT=`5"u.'wrZ(`E5Qm='X:i6|2{h=[^?aK$#!;N%CljIb`5J2uX6; Your doctor should order a pregnancy test before you start this medication. Use Caution/Monitor. CTC Version 2.0 Publish Date: April 30, 1999 Cancer Therapy Evaluation Program 1 Revised March 23, 1998 Common Toxicity Criteria, Version 2.0 DCTD, NCI, NIH, DHHS March 1998 Use Caution/Monitor. Modify Therapy/Monitor Closely. Brentuximab vedotin desensitization in a patient with refractory Hodgkin's lymphoma. Monitor Closely (1)trastuzumab, brentuximab vedotin. . To lower your risk, your doctor may add a medication and tell you to drink plenty of fluids. Specifically, the CTCAE scale leaves much room for subjectivity and does not discern the clinically relevant findings that define immune effector cell-mediated events from nonspecific ones. Adjust dose according to prescribing information if needed. These 31 patients generally presented with either nervous system disorders such as syncope, dizziness, peripheral neuropathy, and hypotonia that seemed distinct from and did not raise clinical suspicion of encephalopathy, or psychiatric disorders such as anxiety and insomnia (Table 2). Use Caution/Monitor. elagolix will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid. Each vial contains 50 mg of brentuximab vedotin. Serious - Use Alternative (1)ivosidenib will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.Serious - Use Alternative (1)tucatinib will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Fifteen minutes later, the symptoms of chest pain and shortness of breath persisted, so hydrocortisone at 100 mg IV was administered, with an additional 25 mg of IV diphenhydramine and 20 mg of IV famotidine. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. First, NT was regraded by CTCAE criteria retrospectively, giving one overarching CTCAE grade to each patient (eg, overarching CTCAE grade 3 was given for a patient who had the following individual neurological events: grade 3 encephalopathy, grade 2 paresthesia, and grade 1 dyskinesia), and compared with the FDA label. stiripentol will increase the level or effect of brentuximab vedotin by P-glycoprotein (MDR1) efflux transporter. All patients with fever in the setting of chemotherapy-induced neutropenia require immediate medical attention regardless of the toxicity grade. Monitor Closely (1)levoketoconazole increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 1186 0 obj <> endobj Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. %PDF-1.6 % Use Caution/Monitor. Important: The drug information on this page is meant to be educational. Minor/Significance Unknown. Doxorubicin, Vinblastine, Dacarbazine, Brentuximab Vedotin, and Monitor Closely (1)nefazodone increases levels of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. $``bd10 doi: 10.1200/JCO.2011.38.0410. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates. Monitor patients for adverse reactions. Lancet Oncol. . endobj and formulary information changes. . ]KAyQYi!8w;hb N4T'ea=AHU !YlmNv,94c4. C- Upon the emergence of these symptoms, the brentuximab vedotin infusion was held. Criteria for grading on the CTCAE scale vary by toxicity, however by convention, grade 1 typically refers to asymptomatic or mild symptoms not requiring intervention, grade 2 refers to moderate symptoms that interfere somewhat with daily function and where some intervention may be indicated, and grade 3 refers to severe symptoms that interfere . Monitor patients for adverse reactions. Given the clear benefits of brentuximab consolidation in improving progression-free survival post transplant (Moskowitz et al., 2015) in high-risk Hodgkin lymphoma, it was thought the benefit of brentuximab vedotin consolidation outweighed the possible risks of subsequent infusions. Accessibility 113 0 obj <> endobj Two patients received corticosteroids for persistent neurotoxicity after resolution of CRS.26, NT comparison among CTCAE, mCRES, ASTCT, and FDA label. Avoid or Use Alternate Drug. acetazolamide will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. In conclusion, this is the first study to retrospectively apply the CTCAE, mCRES, and ASTCT systems to the same patient data set. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. affecting hepatic/intestinal enzyme CYP3A4 metabolism. We conclude that the CTCAE system is suboptimal for the grading of CAR-T cell therapy-associated NT, as it captures a high number of nonattributable and nonspecific nervous system and psychiatric events. Monitor patients for adverse reactions. Use Caution/Monitor. This regimen was chosen based on the clinical rationale for H1 and H2 blockade, as well as corticosteroid and antipyretic coverage, in the prevention of hypersensitivity reactions, not classified as anaphylaxis. Minor (1)larotrectinib will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. mifepristone will increase the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. endobj Modify Therapy/Monitor Closely. Monitor Closely (1)cenobamate will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. 0 CD30-directed antibody-drug conjugate (ADC) consisting of chimeric IgG1 antibody cAC10, specific for human CD30 and the microtubule disrupting agent, monomethyl auristatin E (MMAE, or vedotin), Conjugate binds to cell expressing the CD30 antigen and forms a complex that is internalized within the cell and MMAE is released; MMAE induces cell cycle (G2/M phase) arrest by binding to tubules and disrupting cellular microtubule network, Peak plasma time: 20-30 min (ADC); 1-3 days (MMAE), Steady-state: 21 days (1.8 mg/kg q3Weeks); 56 days (1.2 mg/kg q2Weeks), Data indicated MMAE metabolism occurs primarily via oxidation by CYP3A4/5, Excretion: Feces and urine (24% of the total MMAE [72% unchanged and recovered in feces]), Do not mix or administer with other medicinal products, Adhere to proper handling, dispensing, and administration of anticancer drugs, Unopened vials: Refrigerate at 2-8C (36-46F) in original carton to protect from light, Diluted solutions or reconstituted vials: Refrigerate at 2-8C (36-46F) for up to 24 hr. hiM!JE%Y}>0G2dh&b5"?f` 1M\'`('PD,)*+Z{-784qZS5'fh [o=]^'W1 2L_:o0aHIX :#HoZl&]{j%jO This drug is available at a higher level co-pay. Monitor patients for adverse reactions. 2022 May 20;12:879391. doi: 10.3389/fonc.2022.879391. Monitor Closely (1)primidone will decrease the level or effect of brentuximab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism.