Patient Management With ADCETRIS™: An Advanced Practice Oncology Nurse Roundtable Discussion

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ADCETRIS™ (brentuximab vedotin), a new CD30-directed antibody-drug conjugate (ADC), was approved by the U.S. Food and Drug Administration (FDA) on August 19, 2011, for the treatment of patients with relapsed or refractory Hodgkin lymphoma (HL) after failure of autologous stem cell transplant (ASCT) or after failure of at least 2 prior multiagent chemotherapy regimens. ADCETRIS is also indicated for the treatment of patients with systemic anaplastic large cell lymphoma (ALCL) after failure of at least 1 prior multiagent chemotherapy regimen.1

With FDA approval, the use of ADCETRIS is expected to expand from the controlled clinical trial setting to hospitals and oncology clinics in communities across the United States. As with any newly approved drug, medical professionals will rely on the clinical trial experience to make informed decisions about prescribing and administering ADCETRIS.

Community oncology nurses can benefit from the perspectives of advanced practice nurses (APNs) involved in clinical trials investigating ADCETRIS. In this article, we employ an interactive format to communicate key product-specific information about adverse event management, dosing and administration, patient education, and peer-to-peer education with the goal of enhancing the knowledge base of community oncology nurses, minimizing risk to the patient, and ultimately, improving health outcomes.

The roundtable convened a group of 3 APNs experienced in managing oncology patients in the clinical trial setting. The roundtable panelists shared their insights and knowledge about management approaches in the treatment of HL and ALCL. The Table shows the self-reported information about their experience in treating patients with ADCETRIS.

Adverse Events With ADCETRIS

As with other anticancer agents, a number of adverse events have been reported with ADCETRIS. The most commonly reported events include peripheral sensory neuropathy, fatigue, nausea, diarrhea, pyrexia, upper respiratory tract infection, neutropenia, vomiting, and cough. For both HL and ALCL, the majority of adverse events have been relatively mild (grade 1 or 2) and manageable.2

Overall, the panel indicated that patients under their care showed similar or slightly lower adverse event rates than what is reported in the ADCETRIS full prescribing information. In the nurses’ experience, adverse event rates were similar for HL and ALCL patients, and no lymphoma-specific patterns were seen. Panelists indicated that the adverse events of most concern to patients were peripheral neuropathy (PN) and neutropenia.

Peripheral Neuropathy – Screening and Evaluation

Because it is the most common adverse event attributable to the use of ADCETRIS2 (as well as many other anticancer agents), oncology practices are sensitive to the development of PN. Of the adverse events attributable to ADCETRIS, peripheral sensory neuropathy and neutropenia have been identified as potentially dose-limiting toxicities.3

In clinical trials, PN was predominantly sensory and cumulative but generally manageable and reversible, rarely leading to discontinuation. The majority of patients experienced improvement or resolution of their symptoms, and dose delay and reduction appeared to mitigate worsening of neuropathy.2

In the following exchange, the APNs making up the panel related their personal experiences in screening and evaluating patients for PN. In the oncology clinics represented by the panel, PN screening is routinely performed by two different clinicians during the patient visit. In detecting early signs of PN, accurate patient self-reported information is considered vital. Interestingly, panelists indicated that some patients may be more forthcoming about reporting PN at baseline because of concerns about discontinuation once treatment is already underway. In asymptomatic patients at baseline, panelists indicated that PN is usually detected between the 4th and 6th cycles of treatment.

According to the panel, patients with PN are typically reassessed during each visit for ADCETRIS treatment (every 3 weeks). An external grading tool, the Common Terminology Criteria for Adverse Events (CTCAE) developed by the National Cancer Institute,4 was cited as the most commonly used instrument to determine the degree of PN in their patients.

The Oncology Nurse-APN/PA (TON): Do the rates of PN reported in the clinical studies differ from your own experience?

Stephanie Thompson:We have seen a little less than what was reported in the ADCETRIS prescribing information (PI).

Amanda Copeland: I would say (the PI) is pretty consistent with what we’ve seen. TON: At which treatment cycle are you beginning to see PN in your patients? Thompson: We are starting to see it around the fourth or fifth cycle. Copeland: I would say around the fifth or the sixth cycle.

TON: What are you doing in terms of screening and detection? You’re all screening for PN prior to patients starting on it, correct? Panel: Yes.

TON: Who is currently performing the screening?

Ellen Neylon: It is done twice when the patients are started on the therapy. The nurse or nurse practitioner first, then the physician screens the patient for PN in the (examination) room.

Copeland: It’s similar for us. The nurse will go over the review system and screen for PN when they put the patient in the exam room. Then when the nurse practitioner goes in, we’ll go into more depth about the signs and symptoms.

TON: Is it difficult to detect the early signs of PN?

Neylon: It can be difficult because the only way you can find out early signs of PN is to ask the patient. You’re at their mercy. I think the patients are a little bit more up-front about having any pain or tingling or numbness at the beginning of the treatment than they are after (ADCETRIS) treatment has started. Once they’ve started treatment it’s a little bit tougher to have them verbalize their neuropathy status because they want to keep getting the medication and they don’t want to jeopardize receiving the drug. That’s a concern – you need to watch out for that and really ask the right questions. However, I haven’t really noticed that patients are holding back much.

Thompson: I’ll agree with that – I think they are pretty honest and tell you how much it’s affecting them.

TON: Is anyone seeing motor neuropathy?

Neylon: We really didn’t see any motor at all. All we’ve seen has really been sensory. Thompson:We have seen some (motor) neuropathy. TON: How do you distinguish between motor and sensory neuropathy?

Thompson: I think that objective patient evaluation may be more helpful in terms of detecting motor neuropathy. It’s just doing strength testing or seeing if they’re able to do fine motor tasks.

TON: When it’s determined that a patient has PN, who grades the severity of the event?

Thompson: It’s either the APN or physician at Siteman. Neylon: At NYU Langone, the nurse and the physician are usually grading it. The physician determines the final grade. Copeland: At M.D. Anderson, it’s the APN or physician determining the grade.

TON: What specific tools are you using for grading? Are they internally developed or something external?

Thompson: External. We primarily use the CTCAE developed by the National Cancer Institute. TON: How frequently do you reevaluate the patient after a dose of ADCETRIS has been withheld or adjusted?

Neylon: We grade all toxicities on each visit. Every 3 weeks, we see the patient and we’ll grade everything. If they had an upper respiratory infection on their prior visit, that will be graded as such as resolving and so on and so forth.

Copeland: It’s the same for us. We do the assessment every cycle, once every 3 weeks, when they come in.

TON: Have you noticed anything that predisposes patients to developing PN in general?

Thompson: I think it depends on their preexisting conditions from prior treatments, how heavily they have been pretreated in the past, and whether they have any comorbidities that may also cause neuropathy, like diabetes, for example.

Neylon: I would also say that it’s mostly the prior therapies and any comorbidities that they have.

Patient Management of Peripheral Neuropathy

The panel reported some differences in the degree to which PN was managed in their respective institutions. In one clinic, about one-third of ADCETRIS patients who developed PN were managed with dose delays or adjustments, while another panelist indicated that neuropathy severity was generally low in her clinic, rarely warranting aggressive management. Each of the 3 panelists indicated that some patients were given gabapentin or pregabalin to relieve neuropathic pain symptoms before resorting to dose delay or adjustment. Low vitamin B-12 levels were suggested as a possible contributor to PN symptoms, and concomitant B-12 therapy was often recommended, according to the APNs. Among the 3 panelists, only 1 indicated that a patient was forced to discontinue ADCETRIS due to PN. The discussion is summarized in the following excerpt:

TON: So how did you manage patients who developed PN during the clinical trials?

Thompson: We did the dose reduction, which helped significantly. If they were having sensory or neuropathic pain, we prescribed Neurontin® (gabapentin) as well.

TON: How many of your patients required a dose adjustment?

Thompson: I would say we needed to dose adjust about 10 combined patients, both HL and ALCL, for PN.

Neylon: I would say we’ve only dose reduced 2 or 3 patients for neuropathy reasons throughout the course of our 20-something patients.

Copeland:We manage PN (with ADCETRIS) very similar to as if they were on conventional chemotherapy. First we try Neurontin and Lyrica® (pregabalin), but we haven’t seen much improvement in PN related to ADCETRIS when using these. And then we’ll dose reduce if we need to, but it’s pretty rare.

Neylon: Sometimes we’ve noticed that vitamin B-12 can help with the PN. So we’ve advised some of our patients to just start them and see if it improves their symptoms or if their symptoms progress more slowly. I think the neurologists at our facility support that as well. That’s usually part of the workup for them.

Thompson: Yes, we also recommend vitamin B-12 for some patients. We check vitamin B-12 levels in any of our patients that complain of new onset numbness, tingling, the sensory stuff in their extremities.

TON:How many of your patients were forced to discontinue ADCETRIS treatment because of any kind of neuropathy?

Thompson: Just 1 patient. That was all. Neylon: I don’t believe we had any patients stopped completely for neuropathy.

Copeland: None of our patients were forced to discontinue.

TON: Do you typically have to skip 1 cycle, or is dose adjustment continuous for the remaining course of therapy? How long does it typically take for the PN to resolve?

Thompson: It varies by patient. We try not to delay the dose for too long because that would affect the treatment response. However, if their PN got to grade 3, which happened in 1 patient, we would reduce the dose for the remainder of therapy. In the patient who had grade 3 neuropathy, it took about 6 months to resolve.

Neutropenia and Other Adverse Events

Patients infrequently developed neutropenia during clinical trials for ADCETRIS, according to the APNs on the panel. However, each panelist reported at least 1 case at their respective institution, with patients exhibiting up to grade 3 symptoms. Patients with grade 3 neutropenia were treated with growth factor, which typically resolved their symptoms without the need to delay or adjust dosing of ADCETRIS.

Panelists indicated that neutropenia was detected via CBC blood testing, which was done at each visit (every 3 weeks), according to one APN. In another clinic, neutropenia was detected when a blood test was performed for a patient concomitantly taking warfarin. It was noted that many patients already have low neutrophil counts at baseline, suggesting that underlying neutropenia may already be an issue when patients initiate therapy.

In terms of other adverse events, only upper respiratory tract infection was mentioned as a potential cause for concern. However, in the 2 or 3 cases seen by the panel, patients were typically afebrile and responded well to concomitant antibiotic therapy. It was noted that pulmonary disease is not uncommon in the HL population.

Nurse-to-Patient Communication

Panelists indicated that they were responsible for most patient counseling at their respective institutions. As part of their activities, they encourage patients to receive proper nutrition and stay well hydrated during treatment. They also discuss the possibility of toxicities developing during treatment. Therefore, patients are encouraged to immediately report any new symptoms that may arise during the course of ADCETRIS therapy. According to the panelists, treatment adherence issues are rare, and patients seem to react well to dosing every 3 weeks.

Most treatment-related information is communicated directly to the patient, although in some cases, APNs will also speak with families and/or caregivers if patients are older. In general, patients were curious about how ADCETRIS was different from other anticancer drugs they had received in the past. Panelists found that many patients, especially younger individuals, had already done considerable research on ADCETRIS before starting treatment. During treatment, these patents often continued to communicate with other patients through social media and medically oriented blogs.

TON: Were you specifically involved in counseling your patients or was that someone else?

Neylon: Yes. The PA (physician assistant) or APN, whoever is seeing the patient, we do all the counseling. Since we didn’t really have many events, there wasn’t that much to counsel about.

TON: Did your patients contact you between office visits? What kind of information did you communicate to them?

Neylon: Most of our HL patients were relatively young. They have been through numerous therapies before, and many of them don’t hesitate to call and tell us about their issues. Others have the mindset that they have been doing this for so long that they don’t need to let us know about small little things until the next visit in 3 weeks. As far as communication goes, we try to keep it straightforward, like we do with our new treatment patients. We just let them know that it’s a new therapy and it’s very targeted as to where the medication is going.

TON: In terms of patient communication, what did you recommend to patients to help them monitor potential toxicities or adverse events?

Neylon: We try to educate them to eat well and stay hydrated as much as possible and just make them aware that there is a possibility of side effects. Let them know that it could happen. If they are aware of it, they can be more knowledgeable and just stay better, whether it be on vitamins or just some kind of prophylactic treatment. We found that the knowledge helped empower many of our patients.

Thompson: Just to tag on to basically was just advising them to report any new problems, again, because it was new therapy, and also to report any new medications just to make sure it didn’t require extra monitoring for potential drugdrug interactions.

TON: Have you experienced any adherence issues?

Neylon: No, I think that patients are pretty good with the every-3-week treatment. Occasionally they may have needed interventions in between, like hydration or blood count checks, but not very often. I think that they were pretty happy with how they felt over the course of the 3 weeks, and there wasn’t really an adherence issue that would hinder them from coming in.

Thompson:With once-every-3-weeks dosing, we have not had adherence issues, unless there was some unforeseen hospitalization, unrelated to the drug.

Copeland:We really haven’t had any patient adherence issues either.

TON: Did you encounter any issues with communicating to families or other caregivers?

Thompson:We did not.

Copeland: No. We found that some patients were really intrigued with how ADCETRIS worked. They would do their own research and ask lots of questions about that. But other than that, patients and families were fine with it. Neylon: They were just kind of curious about what’s different. “Why is this different than what I’ve been getting?” was a common question.

TON: Any differences with communicating with younger patients versus older? (For older patients), was it more conversation with the caregiver?

Thompson: For the older patients, sometimes. They tended to be ALCL patients. TON: So if it’s a younger patient, you are talking directly to them. If not, it might be to a caregiver?

Thompson: Correct.

Copeland: For the most part, we speak directly to the patients. Typically, the younger patients request a little more indepth information about the drug’s mechanism of action. They are communicating via social media...they’re on the Internet, they are doing their own research to educate themselves. Generally speaking, my older patients would prefer to read something on their own, maybe a hard copy of something, and then come back with questions. Everyone is different in how they best process and learn new information. It’s best to tailor to them individually.

Neylon: I think that a lot of our patients are well read, and they are in these little groups on Facebook and other social media. It seems that a lot of them know what other patients have already experienced, and so that gets them concerned and they ask. Without referring to (other patients) by name, they definitely ask us about their issues that they have, whether it be neuropathy, whether it be counts being a problem.

TON: Did your patients express any other concerns when they were being treated with ADCETRIS?

Thompson: They would ask questions such as “How long will it work before I progress?” “How many cycles will I get?” and “If this fails, then what’s the next step?” Those are the kind of recurring questions patients asked about ADCETRIS.

Dosing and Administration

Panelists indicated that other nurses at their respective clinics were responsible for the actual infusion of ADCETRIS to their patients. Nonetheless, they were able to provide insights regarding dosing and administration issues. The recommended dose of ADCETRIS is 1.8 mg/kg administered only as an intravenous infusion over 30 minutes every 3 weeks. Treatment should be continued to a maximum of 16 cycles, disease progression, or unacceptable toxicity.2

The APNs agreed that care was required during reconsti-tution to ensure that patients received the proper dose, particularly for patients weighing more than 100 kg. Two panelists indicated that checking body surface area (BSA) was a technique used to calculate the correct dosage.

ADCETRIS administration was characterized as easy and straightforward. Factors contributing to ease of administration include the short infusion time (30 minutes) and lack of reported patient discomfort during the infusion. In the approximately 155 ADCETRIS patients treated at the clinics represented by the APNs on the panel, only 1 infusion reaction was reported. Dose adjustment of ADCETRIS did not complicate dosing and administration, according to the panel.

Two of the panelists indicated that pretreatment to enhance patient comfort was relatively common prior to the infusion. Diphenhydramine, acetaminophen, and hydrocortisone were mentioned as pretreatment agents. One panelist indicated that pretreatment was not routinely given at her cancer clinic.

Nurse-to-Nurse Education

In terms of helping their colleagues prepare for ADCETRIS in their hospitals or clinics, panelists felt that community nurses were generally experienced and knowledgeable and well equipped to begin infusing the drug. The APNs noted that most community oncology nurses already provide chemotherapy, which is often more toxic and potentially debilitating to patients than ADCETRIS. Ease of administration and the short infusion time were also mentioned. The panelists believed there was value in community nurses educating their patients about the unique qualities of ADCETRIS compared to chemotherapy, particularly in explaining the targeted nature of its mechanism of action.

Potential tools to facilitate the education process included an FAQ (frequently asked questions) document, a PN grading guide based on the CTCAE recommendations, and a manufacturer- sponsored toll-free hotline. The first two items could be combined into one laminated flashcard, according to one panelist.

TON: Is there anything you think is absolutely important to communicate to community and clinic nurses who have limited or no experience with ADCETRIS?

Copeland: Treatment with ADCETRIS isn’t necessarily much different than what they are already doing, in fact, in some ways it is easier. Many oncology patients experience neuropathy, so you just treat (ADCETRIS patients who develop neuropathy) like you would any neuropathy patients and give that same sort of education and same management. As far as dose reductions or delay, the doctor makes the final determination. ADCETRIS isn’t like other anticancer drugs that are extremely debilitating as far as neuropathy goes.

Thompson: I totally agree. Patient assessment is going to be exactly the same. In fact, it should be easier compared to more toxic chemotherapy.

TON: What’s going to be helpful as a support strategy for other nurses who are going to manage these patients? Now it’s no longer in a clinical trial, what can you say to help your peers?

Neylon: They are going to want to educate the patient that it’s not a chemotherapy like they’ve seen in the past that kills all cells that are dividing quickly. It’s a very targeted therapy. I think that that would be really important for nurses who have limited experience with ADCs and ADCETRIS in particular. As far as neutropenia or PN, those are pretty usual side effects that we see with other anticancer regimens. So we are kind of on the lookout for those already.

TON: How did you communicate information about the mechanism of action? Are there visuals that you use?

Neylon: Some sort of a diagram illustrating how the drug actually affects the cell and ultimately delivers the chemotherapy. But I think that something that would be unique (in terms of education) would be explaining how the drug is actually affecting the cancer cells.

Copeland: I draw a cell with some markers on the outside and explain how the drug is going and essentially finding those markers, injecting the toxin into the cell, and killing the cell from within. And that’s how it’s a targeted therapy: it’s picking out that particular marker that’s on the tumor cell.

TON: Are there any tools that you really think would be most important for the nurses?

Thompson: I think that FAQs would be helpful. I don’t think those (community) nurses are necessarily novices, because I think it’s just more of the same in terms of your standard chemotherapy that can cause similar side effects and likely has a harsher toxicity profile than ADCETRIS. Again, I’m a fan of the CTCAE grading system that I mentioned earlier. If the manufacturer would offer a toll-free hotline, that would also be helpful.

TON:Well, I think you’ve definitely all hit it on the head. These are not inexperienced nurses that are giving chemotherapy, generally.

Neylon: The one thing I think that community nurses may not have access to as much as we do in academic settings is the CTCAE guide (for grading neuropathy). And so if there was a handout or some sort of worksheet or something that had on it the PN grading system, it would be helpful. Thompson: (The CTCAE guide) is available online.

Neylon: It’s online as well, but in my experience of going to conferences and talking with other community nurses, not that many people grade. So grading for them is, “Can we give the drug?” or “Can’t we give the drug?” So I think that it just might be a good idea to have something printed with the information on it just to remind them. Maybe it’s a laminated quick-reference flash card so it’s durable and it also has the bullet points to review with the patient. I think that that might be helpful just for community nurses giving ADCETRIS.

TON: Anything for ALCL patients? Because that is a different population, they’re potentially more debilitated or have more comorbidities. Is there anything specific to them you can think of that might be valuable for the nurses who are treating them?

Thompson: Our ALCL patients actually were pretty healthy, middle-aged folks. I think we see more preexisting PN in this population, so we keep a close eye on that. As far as the tools that would be used, I don’t think they would be very different. Regarding the community nurse, I have to say that the nurse coordinators that I worked with were very knowledgeable and would even mix their own chemotherapy. Based on my limited access with the (community oncology nurses), I’m not sure we’re giving them enough credit in terms of their assessment skills.

Copeland: I think you’re right. In my previous experience, the nurses in a community setting were mixing their own chemotherapy.

Neylon: I didn’t want to take away from the community nurses, but I’ve just been doing some talks recently to more rural communities, and I know for a fact that they’re not grading toxicities. And protocols aren’t always clear – they may recommend holding the drug for a certain grade of adverse event, but there’s nothing that explains how to grade. Unless the physician is in tune with that, the nurses that I know and have spoken to definitely do not grade. So for them to stop what they’re doing, look up a grade of a toxicity of a CTC guide that they never use, I just think that would be kind of difficult.

Thompson: I think your suggestion was good. I’m all for using easy access tools when I don’t have time to look at a Palm or go online. When you’re in clinic, there’s no time to go online. I fully support the develop of print materials, and I think if they’re given that information they have the knowledge base and experience to interpret it.


During the roundtable discussion, the 3 APNs on the panel provided insightful and engaging commentary about their experiences with ADCETRIS. Overall, the panel did not foresee any major educational challenges for community oncology nurses using ADCETRIS for the first time. They noted that most of their community-based colleagues were knowledgeable and already routinely administered chemotherapy whose toxicity profiles often present significant management challenges. Therefore, in some ways, they might find ADCETRIS administration and management to be easier than what they were accustomed to. In the panelists’ experience, many patients educate them- selves about their condition. Many younger patients communicate with each other via social media. In terms of patient communication, it is important to convey that adverse events, though not uncommon with ADCETRIS, are generally of mild to moderate severity and are manageable, rarely leading to discontinuation of treatment. Panelists also perceived value in educating their patients about the unique mechanism of action of ADCETRIS to help them understand what makes ADCETRIS stand apart from other treatments they have received in the past.


  1. U.S. Food and Drug Administration. FDA approves Adcetris to treat two types of lymphoma. August 19, 2011. ments/ucm268781.htm. Accessed September 6, 2011.
  2. ADCETRIS [package insert]. Bothell, WA: Seattle Genetics; August 2011.
  3. Younes A, Bartlett NL, Leonard JP, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010;363:1812-1821.
  4. U.S. National Institutes of Health, National Cancer Institute, Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC). December 2010. electronic_applications/ctc.htm. Accessed September 20, 2011
Last modified: February 22, 2023