Secondary Logo

Brentuximab vedotin with AVD shows safety, in the absence of strong CYP3A4 inhibitors, in newly diagnosed HIV-associated Hodgkin lymphoma

Rubinstein, Paul, G.a,b; Moore, Page, C.c; Rudek, Michelle, A.d; Henry, David, H.e; Ramos, Juan, C.f; Ratner, Leeg; Reid, Erinh; Sharon, Eladi; Noy, Arielajfor the AIDS Malignancy Consortium (AMC)

doi: 10.1097/QAD.0000000000001729

Objective: Brentuximab vedotin is a Food and Drug Administration approved anti-CD30 antibody drug conjugate potently active in Hodgkin lymphoma. Trials of brentuximab vedotin with doxorubicin, vinblastine, and dacarbazine (AVD-BV) excluded patients with HIV. We studied the safety of AVD-BV in newly diagnosed HIV-associated classical Hodgkin lymphoma .

Design and methods: Patients diagnosed with stage II–IV HIV-associated classical Hodgkin lymphoma received AVD-BV on days 1 and 15 every 28 days for six cycles. Anti-HIV medications with strong CYP3A4 inhibition were excluded. This phase 1 trial followed a 3+3 dose de-escalation design started with brentuximab vedotin at 1.2 mg/kg with standard dosing of AVD. Dose-limiting toxicities were defined in cycle one.

Results: Seven patients were enrolled with six being evaluable: five of six stage III/IV, three with an international prognostic score at least 4. With no dose-limiting toxicities identified, all six were treated at the 1.2 mg/kg dose. Only five grade (G) three nonhematological adverse events were noted in three patients: pulmonary infection, diarrhea, and peripheral neuropathy. No G4/5 adverse events occurred. PET/computer tomography was negative in five of six after cycle 2 and six of six post therapy. Progression-free survival was 100% at 25 months with all patients in remission. One patient was deemed ineligible for taking ritonavir, a strong CYP3A4 inhibitor, but developed G3/4 adverse events including febrile neutropenia, and pancreatitis and though consented was excluded from all evaluation.

Conclusion: AVD-BV was well tolerated at recommended phase 2 dose of 1.2 mg/kg. Concurrent strong CYP3A4 inhibitors should be avoided. A phase 2 study of AVD-BV is currently enrolling (NCT01771107).

aJohn H. Stroger Jr. Hospital of Cook County (Cook County Hospital)

bThe Ruth M. Rothstein CORE Center, Rush University Medical Center, Chicago, Illinois

cUniversity of Arkansas for Medical Sciences, Little Rock, Arkansas

dSidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland

eAbramson Cancer Center, Pennsylvania Hospital, Philadelphia, Pennsylvania

fSylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida

gWashington University School of Medicine, St. Louis, Missouri

hSan Diego Moores Cancer Center, University of California, La Jolla, California

iCancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, Maryland

jMemorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, New York, USA.

Correspondence to Paul G. Rubinstein, MD, Section of Hematology/Oncology, John H. Stroger Hospital of Cook County, 1900 W. Polk Street, Suite 755, Chicago, Illinois, 60612, USA. Tel: +1 312 864 7277; fax: +1 312 864 9002; e-mail:

Received 4 August, 2017

Revised 4 December, 2017

Accepted 5 December, 2017

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

Back to Top | Article Outline


Patients infected with HIV have an eight to 20-fold increased risk of classical Hodgkin lymphoma (cHL) over the general population [1–3]. Currently, cHL is the second most common non-AIDS-defining cancer and its incidence has increased since the implementation of combined antiretroviral therapy (cART) in the mid-1990s [1,2,4]. HIV-associated classical Hodgkin lymphoma (HIV-cHL) presents typically in patients with CD4+ T-cell counts above 200 cells/μl, and is dominated by the mixed cellularity histologic subtype in contrast to the nodular sclerosis in the non-HIV population [2,3,5,6]. HIV-cHL also presents with higher stages and higher international prognostic scores (IPS) [5,6]. Despite presenting more aggressively, the overall survival (OS) currently is similar to the non-HIV population when treated concurrently with cART [6–8]. Treatment in the upfront setting with anti-HIV therapy has improved the OS from 48% at 2 years to 78% at 5 years for advanced stage HIV-cHL when treated with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) [6–9].

An important aspect of HIV-cHL therapy is the identification of potential cART/chemotherapy interactions. Interactions with chemotherapy have become more pronounced as many cART inhibit or induce CYP450 enzymes or drug transporter like P-glycoprotein, which are important mechanisms of drug distribution and excretion [10–14]. cART/chemotherapy interactions therefore increase toxicity or potentially decrease efficacy [2,3,10–12]. The protease inhibitor ritonavir, a CYP3A4 and P-glycoprotein inhibitor, increases vinblastine-related neuropathy and neutropenia, which is a key component of HIV-cHL treatment [2,3,10–12]. Cobicistat has similar inhibitory effects on CYP3A4 and P-glycoprotein [15]. Newer chemotherapeutic agents are metabolized by the CYP3A4 enzyme or transported by P-glycoprotein [15]. The active chemotherapeutic component of brentuximab vedotin, monomethyl auristatin E, is a sensitive CYP3A4 substrate [13,14]. In addition, antiretrovirals can have overlapping toxicities with chemotherapy. For example, zidovidine can cause severe neutropenia in 8% of patients with advanced AIDS, which is a significant complication for cytotoxic chemotherapy and is thus excluded in multiple HIV-cancer clinical trials including this trial [11]. These interactions emphasize the importance of cancer trials in patients with HIV not just to assess efficacy but also therapy-related toxicity in the presence of antiretroviral therapy.

Advanced stage cHL has a rate of relapse of up to 30% after treatment with front-line chemotherapy, and 10% of newly diagnosed cHL patients will not achieve remission [16]. Thus, new treatments are needed, particularly in the HIV-infected population, as most patients present with higher stage cHL. Brentuximab vedotin is an anti-CD30 antibody drug conjugate attached to the antitubulin agent monomethyl auristatin E, specifically targeting CD30+ cancer cells including the Hodgkin Reed Sternberg cell [17]. A phase 2 study of brentuximab vedotin in 102 patients with refractory disease who relapse after autologous stem cell transplant achieved a 73% response rate with a complete remission rate of 33% and an acceptable safety profile leading to its Food and Drug Administration approval [18]. With a 5-year follow-up, 9% of this high-risk population has remained in remission, without any additional forms of therapy [18].

In the front-line setting, a phase 1 trial of brentuximab vedotin combined with ABVD in advanced stage Hodgkin lymphoma, yielded a rate of overall pulmonary toxicity of 44%. However, when brentuximab vedotin (1.2 mg/kg) was combined with AVD alone, the 3-year failure-free survival was 96% and OS was 100%, without pulmonary complications [19,20]. In addition, just released results from the phase 3 ECHELON-1 study, of ABVD versus AVD+BV, demonstrated a 2 year modified progression-free survival (mPFS) benefit utilizing AVD+BV of 82.1 compared with 77.2% in the ABVD arm [21].

In light of the impressive efficacy in the HIV-negative population, we designed a phase 1/2 study utilizing AVD-BV in the front-line setting for HIV-associated cHL. Here we present the phase 1 portion of the trial to examine AVD-BV safety, evaluate preliminary efficacy, and define the recommended phase 2 dose and evaluate preliminary efficacy.

Back to Top | Article Outline

Patients and methods

Study population

Patients with untreated CD30-positive HIV-cHL stage II–IV were eligible for study. Diagnoses were confirmed by central pathology review and HIV by enzyme-linked immunosorbent assay (ELISA). Other key eligibility requirements included at least 18 years of age, and a Karnofsky Performance Status more than 30%. All patients were required to be on cART. Individuals had to change to a nonritonavir or noncobisistat-based HIV regimen 7 days prior to therapy, due to its strong CYP3A4 and P-glycoprotein inhibitory properties. Additionally, subjects have to change a nonzidovidine-based HIV regimen 7 days prior to therapy, due to the potential for profound neutropenia. In addition, patients had to meet the following criteria for eligibility: CD4+ T-cell count at least 50 cells/μl, serum creatinine of 1.5 mg/dl or less, absolute neutrophil count at least 1000 cells/μl, and aspartate aminotransferase and alanine aminotransferase three times or less than the upper limit of normal (ULN), cardiac ejection fraction at least 50%, diffusing capacity of the lung for carbon monoxide (DLCO) adjusted for hemoglobin at least 70% and bilirubin 1.5 or less times the ULN unless thought to be secondary to cART, for example, atazanavir, in which case the total bilirubin could be 3.5 or less [11,20,22]. All patients with exposure to hepatitis B, C, or evidence of chronic infection with or without immunity to hepatitis B were permitted on study provided subjects were taking antihepatitis B virus therapy and met parameters for hepatic function.

Back to Top | Article Outline

Study design and treatment

This was an open-label phase 1 study. The latest assessment was approximately 2 years after the last patient was enrolled on the phase 1 portion of the study ( identifier NCT01771107). Patients for the phase 1 were recruited from March 2013 through January 2015. Each site institutional review board approved the study and patients were provided written consent. All research was done in accordance with the precepts of the Helsinki declaration. Brentuximab vedotin was given sequentially just after AVD (AVD-BV) on days 1 and 15 on a 28 day schedule, for six cycles. The study was a 3+3 dose de-escalation design, where brentuximab vedotin was to be studied at doses of 1.2, 0.9, and 0.6 mg/kg in combination with standard dosing of AVD. Prophylaxis for pneumocystis jiroveci with trimethoprim sulfamethoxazole or dapsone was required and granulocyte colony stimulating growth factor (or pegfilgrastim) was administered on days 2–10 and 16–24 of therapy of each cycle. Three participants began at a dose of 1.2 mg/kg. If at least 1 dose-limiting toxicities (DLT) in cycle 1 were encountered, three to six additional participants would be enrolled at the next lowest dose level. This would then be the RP2D as long as no more than one-sixth of the participants experienced a DLT. The DLT in the phase 1 portion of the study was defined as any adverse event resulting in a delay of AVD-BV therapy of at least 7 days during the first cycle of therapy.

Back to Top | Article Outline

Study assessments

Baseline assessments included evaluation of disease-related signs and symptoms, physical examination, and bone marrow biopsy, CD4+ T-cell count, HIV-1 RNA viral load, sedimentation rate, and a multigated acquisition scan or echocardiogram. Imaging included computer tomography (CT) of the neck, chest abdomen, and pelvis and positron emission tomography (PET) at baseline, after cycle 2, and at treatment completion. Treatment evaluations included a history and physical, documentation of cART compliance, CBC and serum chemistries prior to each cycle. CD4+ T-cell count, HIV-1 RNA viral load analysis was performed at the start of cycle 2, 5, end of treatment, and every 3 months afterwards for 1 year. All adverse events were graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. CT scans were also done after study completion every 6 months for 5 years. Bone marrows showing Hodgkin lymphoma were repeated to confirm complete remission. MRI of the brain was required before treatment initiation to exclude progressive multifocal leukoencephalopathy. Staging and response evaluation followed the 2007 Cheson criteria [23]. PET/CT evaluation followed the Deauville criteria, where a score below 4 was considered to be complete radiographic remission.

Back to Top | Article Outline

Statistical analysis

For the phase 1 portion of the study, utilizing the 3+3 dose de-escalation design, a minimum of 6 and a maximum of 18 participants could be enrolled. The primary endpoint of the phase 1 study was the determination of the RP2D. Secondary endpoints included PFS, overall survival (OS), and correlation of response with cycle 2 and post treatment PET/CT scan evaluation. Criteria for early study discontinuation included any diagnosis of progressive multifocal leukoencephalopathy or if more than 30% of the first 10 patients enrolled on the study experienced a G3 neurotoxicity lasting more than 4 weeks. With an underlying probability of grade 3 neuropathy of no more than 10%, the probability of observing more than three participants with grade 3 neuropathy was less than 5%.

Back to Top | Article Outline



Patients for the phase 1 were recruited from March 2013 through January 2015. Patient baseline characteristics can be found in Table 1. Of the six patients enrolled, five were men, the median CD4+ T-cell count was 163 cells/μl (132–289), and a median viral load was 25 copies/μl (20–77). Eighty-three percent of the patients had stage III/IV HIV-cHL, with 60% of the patients having an IPS of at least 4. Three of six subjects had stage IV disease, of which two out of three patients had bone marrow involvement. One ineligible patient excluded for concomitant ritonavir administration was excluded from all statistical analyses and was eventually replaced.

Table 1

Table 1

No DLTs occurred in cycle 1. Based on the 3+3 design, only six patients were required to complete phase 1. The recommended phase 2 dose (RP2D) of brentuximab vedotin was determined to be 1.2 mg/kg and is being utilized currently in the ongoing AVD-BV phase 2 portion of the study.

Back to Top | Article Outline


Treatment-related grade three to five adverse events are listed in Table 2 for all cycles. All adverse events are shown in the online supplement (supplement Table 1, With respect to hematological toxicity, no patient experienced a G4 or G5 adverse events and only one patient developed a G3 neutropenia during treatment. Three patients experienced a G3 nonhematological adverse events: one lung infection after cycle 3, one diarrhea, and two with peripheral neuropathy. The neuropathy was a G3 peripheral motor and sensory neuropathy in one patient and a peripheral motor neuropathy in another, both after cycle 5. Per protocol, treatment was concluded with AVD alone in those patients, and in both cases the neuropathy decreased to a grade 2, 3 months after drug discontinuation. The study was amended to hold brentuximab vedotin for G2 at least peripheral neuropathy, One patient had pneumonia after cycle 3 day 14, and due to a decrease of DLCO, the patient completed therapy with only AVD after cycle 4.

Table 2

Table 2

Back to Top | Article Outline

Effects of chemotherapy on CD4+ T-cell count, viral load, and combined antiretroviral therapy interactions

The median CD4+ T-cell count and viral load for all subjects was 163 cells/μl and 25 copies/μl, respectively. Trends over time of both CD4+ T-cell count and viral load are shown in Tables 3 and 4 respectively. Four of five patients with entry CD4+ T-cell counts below normal, normalized CD4+ T-cell counts by the start of cycle 2. Three of the five with available data maintained or improved the CD4+ T-cell count further by the end of therapy. The HIV-1 viral load was also stable over time. Only one patient, not compliant with cART had an elevation in his viral load (Tables 3 and 4), and a persistently low CD4+ T-cell count. One patient not reporting taking ritonavir from the onset of therapy developed G3 febrile neutropenia and G4 pancreatitis 7 days after treatment initiation and required admission to the intensive care unit. This patient was excluded from all final analysis due to a violation of inclusion criteria.

Table 3

Table 3

Table 4

Table 4

Back to Top | Article Outline


Per CT criteria, 100% of the patients were in complete remission by the end of therapy. Five of six patients (83%) were PET/CT negative after cycle 2, and one patient had a Deauville score of 4. All patients were PET/CT negative after cycle 6, defined as a Deauville score of less than or equal to 3. PFS with a median follow up of 25 months is 100%.

Back to Top | Article Outline


This phase 1 study is the first trial to study AVD-BV in the upfront setting of HIV-cHL. The primary endpoint was safety and determination of the RP2D for the ongoing phase 2 study, currently enrolling. The trial was a 3+3 dose de-escalation design starting at brentuximab vedotin 1.2 mg/kg. With no DLT identified, six patients enrolled. The RP2D of brentuximab vedotin was determined to be 1.2 mg/kg, and is the dose utilized in the ongoing phase 2 study. This dose is identical to brentuximab vedotin dose utilized in the phase 3 ECHELON-1 study, in the non-HIV population [21].

Five G3 nonhematological adverse events occurred to three patients. Two motor neuropathies and one sensory neuropathy presented by cycle 5 and decreased to G2 3 months after brentuximab vedotin discontinuation. One of the patients with a neuropathy also had a G3 diarrhea. A third patient had a G3 lung infection. Brentuximab vedotin was held as the DLCO decreased after the lung infection, per protocol. This DLCO criterion has been since removed from the ongoing phase 2 study, as bleomycin was not included in the regimen. The same modification was made in the non-HIV AVD-BV versus ABVD phase 3, ECHELON-1 trial. Hematological adverse events were not frequent with only one G3 neutropenia reported.

The incidence of neuropathy in our study was higher than the non-HIV studies with AVD-BV [17,20]. However, ABVD studies in advanced stage HIV-cHL have shown a wide variance in G3/4 neuropathy as high as 27% [24,25]. The cART containing strong CYP3A4 inhibitors, like ritonavir or cobisitat, were not excluded nor reported [24]. In a study excluding ritonavir, G3/4 neuropathy did not occur when given with ABVD [25]. The high incidence of neuropathy (2/6 patients) observed in this study could be due to the use of dual microtubule chemotherapeutic agents, vinblastine and MMAE, though this will be better defined in the ongoing phase 2 study. As a whole, all adverse events were manageable in the phase 1 portion of the trial with either with dose delays or dose modifications.

Response to treatment was also encouraging, with 83% of the patients achieving complete remission by PET/CT post cycle 2, and all in complete remission by end of therapy, with 100% PFS at a median follow-up of 25 months.

The target of brentuximab vedotin, CD30, has been indirectly associated with the potential mechanism of increased HIV viral replication. sCD30 expression in T cells correlated with high viral loads and clinical outcomes in the precART era [26–29]. In addition, both agonistic anti-CD30 antibodies and CD30L-expressing, glutaraldehyde-fixed CD8+ human T-cell clones significantly enhanced HIV expression in human CD4+ T cells obtained from HIV-infected individuals [28]. Thus, it is notable that in our study the CD4+ T-cell count and viral load were not adversely affected over time during treatment. In fact, in four of five patients with entry CD4+ T-cell counts below normal, normalized their CD4+ cell count by the start of cycle 2. The low CD4+ T-cell counts at treatment onset could be due to Hodgkin lymphoma related lymphopenia; however, historic CD4+ T-cell counts were not captured.

cART chemotherapy interactions are also important. One patient did not report taking CYP3A4 inhibitor ritonavir, violating the inclusion criteria, and was excluded from all analysis, and was replaced by another participant. This patient subsequently developed G3 febrile neutropenia and G4 pancreatitis, all before the initiation of cycle 2. The timing of pancreatitis was consistent with the data published by Winter et al. where four of eight cases of pancreatitis reported during brentuximab vedotin therapy presented before cycle 2 in this cohort [30]. In the ongoing phase 2 portion of the present study, two other patients were inadvertently exposed to ritonavir. One was admitted to intensive care for febrile neutropenia at the start of cycle 1. The second patient having discontinued ritonavir less than 48 h before therapy initiation and continued the moderate CYP3A4 inhibitor fluconazole, developed a prolonged G3 neuropathy. In one instance, a primary HIV provider had changed the anti-HIV medication without consultation of the treating oncologist. This emphasizes the importance of communication between the oncologist and primary care HIV physician. In the ongoing phase 2 portion, provider letters are now mandated and the protocol team reviews all cART prior to enrollment. We strongly recommend against the use of ritonavir, or any similar anti-HIV medication with strong CYP3A4 or p-glycoprotein inhibitory properties, for example, cobisistat, in combination with brentuximab vedotin or ABVD. Additionally, we also made recommendation for patients taking two moderate CYP3A4 inhibitors given the concern of additive CYP3A4 inhibition. For the moderate CYP3A4 inhibitors, one of the two drugs must be withheld 7 days prior to treatment initiation and not restarted. Lastly, we are assessing pharmacokinetics in the phase 2 portion to elucidate whether brentuximab vedotin or the warhead (mono-metheyl auristatin E) exposure is altered in the presence of CYP3A4 inducing and noninducing cART regimens.

In conclusion, this phase 1 trial demonstrated safety of the AVD-BV regimen with standard brentuximab vedotin 1.2 mg/kg dosing in HIV-cHL. In the general population, a 3 year OS of 100% was observed in a phase 1 trial [16]. AMC 085 has at 25 months, a PFS of 100% with manageable adverse events. The phase 2 trial, in conjunction with the French lymphoma study association, LYSA, is enrolling.

Back to Top | Article Outline


P.G.R., P.M. J.C.R., M.A.R., D.H., L.R., and A.N. are members of the AIDS Malignancy Consortium and their effort in addition to this clinical trial was supported in part by NIH grant # UM1 CA121947. P.G.R., P.M., J.C.R., M.A.R., D.H., L.R., E.S., and A.N. all played a role in the study design and manuscript preparation.

This work was funded by the National Institutes of Health, Grant # UM1CA121947.

Back to Top | Article Outline

Conflicts of interest

There are no conflicts of interest reported by any of the authors.

Back to Top | Article Outline


1. Shiels MS, Pfeiffer RM, Gail MH, Hall HI, Li J, Chaturvedi AK, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst 2011; 103:753–762.
2. Rubinstein PG, Aboulafia DM, Zloza A. Malignancies in HIV/AIDS: from epidemiology to therapeutic challenges. Aids 2014; 28:453–465.
3. Uldrick TS, Little RF. How I treat classical Hodgkin lymphoma in patients infected with human immunodeficiency virus. Blood 2015; 125:1226–1235.
4. Biggar RJ, Jaffe ES, Goedert JJ, Chaturvedi A, Pfeiffer R, Engels EA. Hodgkin lymphoma and immunodeficiency in persons with HIV/AIDS. Blood 2006; 108:3786–3791.
5. Spina M, Carbone A, Gloghini A, Serraino D, Berretta M, Tirelli U. Hodgkin's disease in patients with HIV infection. Adv Hematol 2011; 2011: pii: 402682. doi:10.1155/2011/402682.
6. Besson C, Lancar R, Prevot S, Brice P, Meyohas MC, Marchou B, et al. High risk features contrast with favorable outcomes in HIV-associated Hodgkin lymphoma in the modern cART era, ANRS CO16 LYMPHOVIR Cohort. Clin Infect Dis 2015; 61:1469–1475.
7. Montoto S, Shaw K, Okosun J, Gandhi S, Fields P, Wilson A, et al. HIV status does not influence outcome in patients with classical Hodgkin lymphoma treated with chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine in the highly active antiretroviral therapy era. J Clin Oncol 2012; 30:4111–4116.
8. Olszewski AJ, Fallah J, Castillo JJ. Human immunodeficiency virus associated lymphomas in the antiretroviral therapy era: Analysis of the National Cancer Data Base. Cancer 2016; 122:2689–2697.
9. Levine AM, Li P, Cheung T, Tulpule A, Von Roenn J, Nathwani BN, Ratner L. Chemotherapy consisting of doxorubicin, bleomycin, vinblastine, and dacarbazine with granulocyte-colony stimulating factor in HIV-infected patients with newly diagnosed Hodgkin's disease: a prospective, multiinstitutional AIDS clinical trials group study (ACTG 149). J Acquir Immune Defic Syndr 2000; 24:444–450.
10. Rubinstein PG, Braik T, Jain S, Orsi J, Gupta S, Itokazu G, et al. Ritonavir based highly active retroviral therapy (HAART) correlates with early neurotoxicity when combined with ABVD treated HIV associated Hodgkin lymphoma but not non-Hodgkin lymphoma. A retrospective study. Blood 2010; 116:2807–12807.
11. Rudek MA, Flexner C, Ambinder RF. Use of antineoplastic agents in patients with cancer who have HIV/AIDS. Lancet Oncol 2011; 12:905–912.
12. Ezzat HM, Cheung MC, Hicks LK, Boro J, Montaner JS, Lima VD, et al. Incidence, predictors and significance of severe toxicity in patients with human immunodeficiency virus-associated Hodgkin lymphoma. Leuk Lymphoma 2012; 53:2390–2396.
13. ADCETRIS (Seattle Genetics, Inc.): FDA Package Insert -
14. Walubo A. The role of cytochrome P450 in antiretroviral drug interactions. Expert Opin Drug Metab Toxicol 2007; 3:583–598.
15. Hossain MA, Tran T, Chen T, Mikus G, Greenblatt DJ. Inhibition of human cytochromes P450 in vitro by ritonavir and cobicistat. J Pharm Pharmacol 2017; 69:1786–1793.
16. Kuruvilla J. Standard therapy of advanced Hodgkin lymphoma. Hematology (Am Soc Hematol Educ Program) 2009; 2009:497–506.
17. Alperovich A, Younes A. Targeting CD30 using brentuximab vedotin in the treatment of Hodgkin Lymphoma. Cancer J 2016; 22:23–26.
18. Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma. Blood 2016; 128:1562–1566.
19. Younes A, Connors JM, Park SI, Fanale M, O’Meara MM, Hunder NN, et al. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol 2013; 14:1348–1356.
20. Connors JM, Ansell S, Park SI, Fanale MA, Younes A. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed advanced stage Hodgkin lymphoma: long term outcomes. Blood 2014; 124:292.
21. Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, et al. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med 2017; Dec 10. doi: 10.1056/NEJMoa1708984.
22. Antoniou T, Tseng AL. Interactions between antiretrovirals and antineoplastic drug therapy. Clin Pharmacokinet 2005; 44:111–145.
23. Barrington SF, Mikhaeel NG, Kostakoglu L, Meignan M, Hutchings M, Mueller SP, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. J Clin Oncol 2014; 32:3048–3058.
24. Hentrich M, Berger M, Wyen C, Siehl J, Rockstroh JK, Müller M, et al. Stage-adapted treatment of HIV-associated Hodgkin lymphoma: results of a prospective multicenter study. J Clin Oncol 2012; 30:4117–4123.
25. Sandhu S, Gupta S, Itokazu G, Braik T, Jain S, French AL, Rubinstein PG. Prevention of adverse events during treatment of HIV-associated Hodgkin lymphoma with ritonavir and zidovudine. J Clin Oncol 2012; 30, (suppl; abstr 8085).
26. Pizzolo G, Vinante F, Morosato L, Nadali G, Chilosi M, Gandini G, et al. High serum level of the soluble form of CD30 molecule in the early phase of HIV-1 infection as an independent predictor of progression to AIDS. AIDS 1994; 8:741–745.
27. Rizzardi GP, Barcellini W, Tambussi G, Lillo F, Malnati M, Perrin L, Lazzarin A. Plasma levels of soluble CD30, tumour necrosis factor (TNF)-§ and TNF receptors during primary HIV-1 infection: correlation with HIV-1 RNA and the clinical outcome. AIDS 1996; 10:F45–F50.
28. Maggi E, Annunziato F, Biagiotti R, Giudizi MG, Ravina A, Almerigogna F, et al. Activation of HIV expression by CD30 triggering in CD4 + T cells from HIV infected individuals. Immunity 1995; 3:251–255.
29. Pizzolo G, Vinante F, Nadali G, Krampera M, Morosato L, Chilosi M, et al. High serum level of soluble CD30 in acute primary HIV-1 infection. Clin Exp Immunol 1997; 108:251–253.
30. Gandhi MD, Evens AM, Fenske TS, Hamlin P, Coiffier B, Engert A, et al. Pancreatitis in patients treated with brentuximab vedotin: a previously unrecognized serious adverse event. Blood 2014; 123:2895–2897.

antibody drug conjugate; HIV-associated Hodgkin lymphoma; targeted therapy

Supplemental Digital Content

Back to Top | Article Outline
Copyright © 2018 Wolters Kluwer Health, Inc.