**Managing Unique Toxicities and Immune-Related Adverse Effects of Treatment for Hodgkin Lymphoma — Transcript & Summary | SozAI**
Source: https://sozai.app/transcript/hodgkin-lymphoma-treatment-toxicities-immune-adverse-effects/

NCCN CE expert talk on managing advanced-stage classic Hodgkin lymphoma: shifting paradigms, SWOG 1826, ECHELON-1 and HD21 data, and immune/unique toxicities.

## Key Takeaways

- Front-line choice in advanced classic Hodgkin lymphoma now favors BV-AVD, Nivo-AVD, or BrECADD over older regimens in appropriate patients.
- PET-adapted de-escalation (e.g., RATHL) remains a valid strategy where novel agents are unavailable or unsuitable.
- Brentuximab causes peripheral neuropathy, and checkpoint inhibitors cause immune-related toxicities that need early recognition and management.
- Autoimmune disease history such as lupus requires careful risk-benefit assessment before checkpoint inhibitor use.

## What the video covers

- Presenters from Stanford walk through a 34-year-old woman with advanced-stage classic Hodgkin lymphoma and lupus as a case to frame front-line treatment choices.
- Treatment paradigm for advanced-stage classic Hodgkin lymphoma has shifted with novel agents, moving from PET-adapted escalation/de-escalation toward brentuximab vedotin and checkpoint inhibitor regimens.
- ECHELON-1 showed a progression-free survival and first overall survival advantage for BV-AVD over ABVD, with 83% vs 76% PFS at 5-6 years.
- SWOG 1826 compared nivolumab-AVD with ABVD and is the only randomized trial of a checkpoint inhibitor in this setting.
- German HD21 trial evaluated BrECADD versus escalated BEACOPP, with BrECADD showing better tolerability and efficacy in many patients.
- NCCN recommendations changed in 2025 once full publications appeared, making Nivo-AVD and BrECADD category 1 preferred regimens.
- PET-adapted approaches such as RATHL allow de-escalation (dropping bleomycin) in interim PET-negative patients without loss of outcomes.
- Unique toxicities include pulmonary toxicity from bleomycin, peripheral neuropathy from brentuximab, and immune-related adverse events such as pneumonitis, colitis, hepatitis, endocrinopathies, and inflammatory arthritis from checkpoint inhibitors.
- Pre-existing autoimmune disease such as lupus increases the risk and severity of immune adverse events, a key consideration for this patient.
- The session includes audience polling and Q&A on cardiac monitoring, doxorubicin cumulative dose, and pembrolizumab versus nivolumab outcomes.

## Chapters

1. 00:00 Introduction and Learning Objectives
2. 03:00 Case Presentation and Polling
3. 06:51 Front-Line Trial Data: ECHELON-1, SWOG 1826, HD21
4. 20:55 PET-Adapted Approaches and RATHL
5. 27:50 Unique Toxicities: Brentuximab and Checkpoint Inhibitors
6. 38:10 Immune-Related Adverse Events and Management
7. 51:10 Audience Questions and Discussion

Answers

## Questions about this video

What changed in the NCCN recommendations for advanced classic Hodgkin lymphoma?

Recommendations initially placed BrECADD and Nivo-AVD as category 2A/2B options because only abstracts were available. After full publications of the trials, the 2025 update made Nivo-AVD and BrECADD category 1 preferred regimens.

What did ECHELON-1 show compared with ABVD?

ECHELON-1 showed a progression-free survival advantage for BV-AVD (83% vs 76% at five to six years) and the first overall survival advantage among these front-line trials.

Why is lupus relevant to this patient's treatment?

Pre-existing autoimmune disease increases the rate, earliness, and severity of immune-related adverse events from checkpoint inhibitors, and such patients may need high-dose glucocorticoids or discontinuation.

## Full Transcript — Download SRT & Markdown

00:05

Speaker A

So, thank you everyone for joining. Uh, uh, Chandni and I work very closely together at Stanford, and we're uh, delighted that we can uh, walk you through what, how we practice in many ways.

00:18

Speaker A

The learning objectives are describe how the treatment paradigm for advanced stage classic Hodgkin's has shifted in recent years. Discuss the key results of the SWOG 1826, ECHELON 1, and the German Hodgkin Study Group HD21 studies.

00:33

Speaker A

The learning objectives are: describe how the treatment paradigm for advanced stage classic Hodgkin's has shifted in recent years. Discuss the key results of the SWOG 1826, ECHELON 1, and the German Hodgkin Study Group HD21 studies.

00:42

Speaker A

We'll start out with one of the cases which Chandni and I have managed. It's a 34-year-old female who presents with drenching night sweats and left neck adenopathy. Her PET CT shows left cervical supraclavicular mediastinal left axillary adenopathy, splenic, and bone lesions. A

01:00

Speaker A

Identify unique toxicities of brentuximab vedotin and the checkpoint inhibitors such as nivolumab or pembrolizumab.

01:13

Speaker A

Her past medical history is significant for systemic lupus, which is currently well controlled on hydroxychloroquine.

01:25

Speaker A

We'll start out with one of the cases which Chandni and I have managed. It's a 34-year-old female who presents with drenching night sweats and left neck adenopathy.

01:30

Speaker A

ABVD per RATHL, it would be a PET-adapted approach. BV AVD per the ECHELON 1 trial. Nivo AVD per the SWOG 1826 trial.

01:41

Speaker A

Her PET CT shows left cervical, supraclavicular, mediastinal, left axillary adenopathy, splenic, and bone lesions. A biopsy from the neck reveals classic Hodgkin lymphoma.

01:59

Speaker A

About 50% than 50% 44 Nivo-AVD 1826 and just 1% with BrECADD which is the uh German regimen. So, it's a split between sort of three main choices and let's go over the data.

02:14

Speaker A

Her IPS score is four based on stage four, hemoglobin, albumin, and a WBC of 15,000.

02:29

Speaker A

category 1. And useful under certain circumstances was BrECADD or the Nivo-AVD. And they both were sort of category either 2A or 2B and the reason being that these had just been presented at meetings in an abstract form and we didn't really have

02:46

Speaker A

Her past medical history is significant for systemic lupus, which is currently well controlled on hydroxychloroquine.

02:59

Speaker A

publications came out, you can see that in 2025 the recommendations flipped completely where now the preferred regimens are actually Nivo-AVD as well as BrECADD uh per the German Hodgkin uh HD21 trial and both are category 1. And what switched to useful under certain

03:19

Speaker A

How would you treat this patient? This is the first polling question, so go ahead and poll.

03:38

Speaker A

de-escalation. And the RATHL trial is an example of that. It did include stage 2 patients, but basically if you were interim PET-negative defined as a Deauville score of 1, 2, or 3, you could safely drop the bleomycin and just

03:53

Speaker A

ABVD per RATHL, it would be a PET-adapted approach. BV AVD per the ECHELON 1 trial. Nivo AVD per the SWOG 1826 trial.

04:08

Speaker A

In Europe they started out with escalated BEACOPP and if you are PET negative you could drop down to ABVD times four. So again sparing the extra toxicity of an additional four cycles of escalated BEACOPP which at that time was

04:23

Speaker A

Brexanolone per the German Hodgkin Study Group HD21 trial. I think.

04:37

Speaker A

mature follow-up there was no difference in outcome. So suggesting that using an interim PET we can safely de-escalate therapy who have a PET negative scan.

04:47

Speaker A

So, here are the answers. So, about 20% voted for treating with ABVD per RATHL. About 35% voted treating per ECHELON 1 with BV AVD.

05:02

Speaker A

positive patients therapy was escalated to BEACOPP and you can see that their outcomes even if are are about the in the 60% range. So not as good as the ones with PET positive but still pretty good.

05:16

Speaker A

About 50%, than 50%, 44% Nivo-AVD 1826, and just 1% with BrECADD, which is the German regimen.

05:30

Speaker A

Similarly with the LISA trial which started out with escalated BEACOPP you can see at a median follow-up of over five years now that the PFS is almost hitting 986 to 90% and this is the German Hodgkin 18 trial which did

05:45

Speaker A

So, it's a split between sort of three main choices, and let's go over the data.

06:04

Speaker A

where we have learned a lot more about the biology of Hodgkin's, and we've learned how to harness the immune system in managing Hodgkin's. So, one, of course uh the development of brentuximab, which was an antibody-drug conjugate, and I'm

06:19

Speaker A

So, the front-line management has evolved, and I can tell you that in 2024, when we had our panel meeting, the preferred regimens were ABVD per RATHL or using brentuximab AVD per the ECHELON 1 trial, and you can see that's category 1.

06:34

Speaker A

The other class of drugs are the checkpoint inhibitors, and nivolumab and pembrolizumab are such two drugs. It builds on the biology of Hodgkin's, where we know that the Reed-Sternberg cell have a genetic alterations of 9p24, and containing PD ligands, and express

06:51

Speaker A

And useful under certain circumstances was BrECADD or the Nivo-AVD. And they both were sort of category either 2A or 2B, and the reason being that these had just been presented at meetings in an abstract form, and we didn't really have the full manuscript published, so we didn't know the details of that regimen.

07:04

Speaker A

So, with these approval of novel agents, treatment paradigms continue to evolve. So, the ECHELON-1 trial was the first randomized trial looking at a novel agent, and randomized BV AVD to ABVD straight for six cycles. This was not PET-adapted. It was a global trial, and

07:20

Speaker A

And in general, we try to make sure that it's very well vetted before it comes as a mainstream guideline.

07:30

Speaker A

And you can see the ECHELON-1 outcomes now at five to six years. There is a progression-free survival advantage for BV AVD, 83% versus 76% for ABVD. And more than ever, for the first time ever we saw a overall survival advantage 94%

07:48

Speaker A

And literally six to seven months later, when those publications came out, you can see that in 2025 the recommendations flipped completely, where now the preferred regimens are actually Nivo-AVD as well as BrECADD, per the German Hodgkin HD21 trial, and both are category 1.

07:57

Speaker A

This regimen really did not help patients over 60 because there was a fair amount of toxicity and those delays. So over 60 ABVD was just as good. So this kind of quickly became the standard of care in the US. So it was

08:10

Speaker A

And what switched to useful under certain circumstances was the brentuximab AVD or the ABVD per RATHL.

08:31

Speaker A

When this trial was designed it was a leap of faith that the ECHELON-1 trial would be positive in favor of BV AVD and that's why it was used as a control arm and it was again to mimic the ECHELON-1 it

08:45

Speaker A

So, you know, we spent an era, almost a decade, looking at PET-adapted approaches in Hodgkin's, where we tried to select a subset of patients who might benefit from therapy escalation or de-escalation.

09:02

Speaker A

And you can see in the safety outcomes that the arm with NIVO AVD did quite well. There was more Growth factor was mandated in the BV AVD arm. So almost everybody 97% got it.

09:16

Speaker A

And the RATHL trial is an example of that. It did include stage 2 patients, but basically, if you were interim PET-negative, defined as a Deauville score of 1, 2, or 3, you could safely drop the bleomycin and just continue with ABVD times four, and at mature follow-up there was no difference in outcomes.

09:30

Speaker A

otherwise the rest of the arms the toxicity was very mild and quite well tolerated.

09:36

Speaker A

The progression-free survival was just about as good with ABVD and much lower pulmonary toxicity. So that was very appealing.

09:50

Speaker A

The benefit is seen across all age groups. You can see it prolongs it in adolescence. It prolongs it in the 18-60 year olds, 91% versus 86%.

10:03

Speaker A

In Europe they started out with escalated BEACOPP, and if you are PET negative, you could drop down to ABVD times four. So again, sparing the extra toxicity of an additional four cycles of escalated BEACOPP, which at that time was the standard of care.

10:17

Speaker A

I think where it has been immediately practice-changing has been for patients over 60 because over here you can see dramatic response in PFS advantage, 82% versus 58% and not only that, even a overall survival advantage, 96% versus 85%. And the reason mainly being there

10:37

Speaker A

And then the German Hodgkin 18 study evaluated giving even less of escalated BEACOPP, four cycles instead of six to eight, which they had done traditionally, if you were interim PET negative, and again at mature follow-up there was no difference in outcome.

10:51

Speaker A

So moving on to the BrECADD regimen, which was HD21, while the US Intergroup looked at checkpoint inhibitors with AVD, the Germans incorporated Brentuximab in trying to make escalated BEACOPP a much safer and better tolerated regimen. So what they did is

11:08

Speaker A

So, suggesting that using an interim PET, we can safely de-escalate therapy for those who have a PET-negative scan.

11:23

Speaker A

so that you could have the chemotherapy effect. There was no vincristine because they added Brentuximab. They got rid of procarbazine, which was leukemogenic, and substituted it with dacarbazine, which is an alkylator, and they got rid of the 14 days of prednisone, which was

11:39

Speaker A

This is just the Kaplan-Meier curves for the RATHL trial, where you dropped the bleomycin from the ABVD. You can see the curves completely overlap for progression-free survival and overall survival.

11:50

Speaker A

Again, infertility was a big issue with the escalated BEACOPP, and as you know, the Hodgkin's is a disease of young with a median age of 30, and you really want to preserve fertility, and that was one of the reasons why escalated BEACOPP did

12:04

Speaker A

And for the PET-positive patients, therapy was escalated to BEACOPP, and you can see that their outcomes, even if about in the 60% range, are not as good as the ones with PET-negative, but still pretty good.

12:18

Speaker A

Efficacy-wise also, 5-year efficacy has been presented, and you can see that at 5 years, the median progression-free survival is in favor of BRECADD at 94%, and even in PET-positive patients, where instead of getting just four cycles, they get six cycles, you

12:35

Speaker A

This is RATHL outcomes by stage. About 40% of the patients had stage two bulky disease, and the seven-year follow-up shows a PFS of about 85% and an excellent overall survival of about 95%.

12:51

Speaker A

BRECADD with brentuximab as an A+ 21, and that's why they are in both as category one in the NCCN guidelines. So, as I told you, our patient we decided to choose Nivo AVD. So, Chandni, can you walk us through, you know, when we are

13:06

Speaker A

Similarly, with the LISA trial, which started out with escalated BEACOPP, you can see at a median follow-up of over five years that the PFS is almost hitting 86 to 90%.

13:21

Speaker A

Yeah, thanks, Anjana. So, you know, in general, checkpoint inhibitor toxicity is rare, um, we can see here from both the figures. With most of the side effects occurring less than 10% of the time, aside from fatigue, rash, and

13:36

Speaker A

And this is the German Hodgkin 18 trial, which did four cycles of escalated BEACOPP. Again, with very mature follow-up, you can see progression-free survival with four cycles in the 95% range.

13:51

Speaker A

patients about potential side effects of treatment, uh, beyond the typical chemotherapy symptoms. So, some of the key points that I usually include when educating patients that are going to be starting on a checkpoint inhibitor-based regimen, is that any side effect needs a high index

14:09

Speaker A

So, honestly, very good results with all of these approaches, escalated BEACOPP having a slightly more progression-free survival advantage.

14:18

Speaker A

I do in- tell them about rash, um, I tell them about diarrhea. Those are the things that happen most commonly, but again, if they have chest pain, if they have headache, if they have a cough, these are things that we need to know

14:31

Speaker A

But then, we're in an era now where we have learned a lot more about the biology of Hodgkin's, and we've learned how to harness the immune system in managing Hodgkin's.

14:42

Speaker A

help monitor things that may not be immediately symptomatic, like thyroid, adrenal, or cardiac dysfunction.

14:51

Speaker A

So, one, of course, is the development of brentuximab, which was an antibody-drug conjugate, and I'm sure the audience knows quite well. It targets CD30, which is expressed on Reed-Sternberg cells, and it's approved right now for relapsed-refractory disease, in advanced-stage frontline disease with AVD, and as maintenance post-transplant.

15:04

Speaker A

do you how do we grade these? How do we manage these? Yeah, so these are some guidelines on grading and management adapted from NCCN's recommendations. And starting with rash, which we know is a side effect we see pretty commonly in our

15:21

Speaker A

The other class of drugs are the checkpoint inhibitors, and nivolumab and pembrolizumab are two such drugs. It builds on the biology of Hodgkin's, where we know that Reed-Sternberg cells have genetic alterations of 9p24 and contain PD ligands and express PD-L1.

15:35

Speaker A

total body surface area, and the rash wasn't affecting any activities of daily living. So, we graded it as a grade one and started a moderate potency topical steroid. Usually, we use triamcinolone and continued her immunotherapy.

15:51

Speaker A

So, binding of PD-1 to its ligands inhibits T-cell activation and allows tumors to evade the immune response. So, if you block that immune evasion pathway, you can restore anti-tumor responses.

16:08

Speaker A

isn't restarted in this case until the rash improves to a grade one. For hepatobiliary toxicity, the degree of grading here is based on the AST and ALT elevation. So, in our patient's case with the upper limit of both the AST and

16:26

Speaker A

So, with the approval of these novel agents, treatment paradigms continue to evolve. The ECHELON-1 trial was the first randomized trial looking at a novel agent, and it randomized BV AVD to ABVD straight for six cycles.

16:35

Speaker A

For all patients, we also want to rule out viral etiology and then also assess for any alcohol, acetaminophen, or other hepatotoxic supplement use.

16:45

Speaker A

This was not PET-adapted. It was a global trial, and this was not ABVD per RATHL. The bleomycin continued irrespective of whether the PET was positive or not, because this was not PET-adapted.

16:58

Speaker A

Treatment for immune checkpoint inhibitor-related hypothyroidism is based on the degree of TSH elevation and is treated with levothyroxine when the TSH goes above 10 or the patient becomes symptomatic.

17:11

Speaker A

And you can see the ECHELON-1 outcomes now at five to six years. There is a progression-free survival advantage for BV AVD, 83% versus 76% for ABVD.

17:27

Speaker A

rare, but in this case the TSH may be lower normal and the T4 will also be low.

17:36

Speaker A

And more than ever, for the first time ever, we saw an overall survival advantage, 94% versus 89%, with the BV AVD arm. It took about six years to manifest, but nonetheless, there was a survival advantage.

17:46

Speaker A

And again, in general, hypophysitis is a very rare side effect, but in patients that are presenting with unexplained dizziness, lethargy, or headache or vision changes, they should be considered checking for other pituitary hormones such as ACTH, FSH, or LH. And again, if

18:05

Speaker A

This regimen really did not help patients over 60, because there was a fair amount of toxicity and those delays. So over 60, ABVD was just as good.

18:22

Speaker A

movements per day over baseline and also interference with ADLs. The initial workup should include a fecal calprotectin, which is a non-invasive proxy for assessing mucosal inflammation. And if this is positive, you would automatically treat it as at least a grade two, which would require

18:41

Speaker A

So this quickly became the standard of care in the US. So it was RATHL or ECHELON-1. And in Europe it became escalated BEACOPP.

18:55

Speaker A

If the colitis is refractory to steroids, then you can consider adding infliximab or vedolizumab, or as a third line tofacitinib which is a JAK inhibitor, or an anti-IL-12 monoclonal antibody.

19:11

Speaker A

So now, with the advent of nivo and new trials, these became evaluated. The 1826 trial looked at Nivo-AVD for six cycles and compared it to BV AVD per the ECHELON-1.

19:21

Speaker A

Another side effect that we see pretty commonly in clinic is oral mucositis, especially when we're using a combined regimen with a checkpoint inhibitor and chemotherapy.

19:30

Speaker A

When this trial was designed, it was a leap of faith that the ECHELON-1 trial would be positive in favor of BV AVD, and that's why it was used as a control arm. It was again to mimic the ECHELON-1; it was restricted to patients with stage three or four disease.

19:34

Speaker A

And starting with grade two, immunotherapy should be held. We check HSV serologies for all patients that are starting treatment, um and we do start acyclovir prior if they screen positive. We also want to educate all of our patients on the importance of good

19:51

Speaker A

It excluded patients who had interstitial lung disease or pneumonitis. It also excluded patients with pre-existing rheumatological disease, and it excluded patients who had peripheral neuropathy.

20:02

Speaker A

Thanks, Shanley. So, you know, these are the most common ones which you described. So, actually, who is at risk for these immune-related AEs in the real-world setting? So, this was a large study of 16,000 US patients, and higher

20:16

Speaker A

And you can see in the safety outcomes that the arm with Nivo-AVD did quite well. Growth factor was mandated in the BV AVD arm, so almost everybody, 97%, got it, whereas in the Nivo-AVD arm only half the patients got it, because it was optional, and that might explain the sligh

20:33

Speaker A

toxicity. Of course, we don't really have long-term data in a frontline therapy because it's just been approved, and all the data we have is largely from solid tumors.

20:44

Speaker A

So, this review in this paper looked at the immune-related adverse events in frontline therapies, and you can see that depending on the study at this included the early stage as well as advanced stage, and you can this is the Nivo AVD study

20:59

Speaker A

which we just talked about. The rest are with Pembro, and you can see that for grade three, depending on what it is, about to anywhere from 20% of patients had greater than grade three. Here it was 76% greater than grade two. Here it

21:13

Speaker A

was 80% greater than any grade three. Now, grade three doesn't necessarily mean it was life-threatening. It could just have been a, you know, the chemotherapy part of it. They didn't really sort it out, but they thought it was immune-related. Well, more like the

21:27

Speaker A

rash, the diarrhea, those common things. So, it's not uncommon. While the overall study showed that the incidence of grade three was not that high, but I think this is something where we have to really think about as we're using these

21:40

Speaker A

agents more and more, because it's going to impact how we manage the dosing, when to stop it, when not to stop it.

21:47

Speaker A

And just to sort of, you know, what caught Chandy and me by surprise is that it can happen, you know, we always think, oh, it'll happen maybe halfway through the therapy or maybe a few months later. We recently had this case

21:58

Speaker A

of a 31-year-old female on nivo AVD for stage four classic Hodgkin lymphoma, and who had presented presents for literally for cycle two day one, two weeks after she completed her first cycle. And she comes in with cough and fatigue and

22:15

Speaker A

a fever. She was tachycardic. She was satting okay, but we did a chest x-ray, and it showed a left lower lobe infiltrate. So, we decided to give her delay her treatment and give her antibiotics. But she showed up, you

22:26

Speaker A

know, a week five days later again with more tachycardia more tachypnea, and her O2 sats were now 95%.

22:34

Speaker A

So, we decided to do a seat chest CT, and I'm going to let Chandy walk you over, you know, the management of this.

22:40

Speaker A

But this clearly is an example of early onset pneumonitis, which happened after just one dose of nivolumab. So, Chandy, can you walk us through the grading and management of all this?

22:51

Speaker A

Yeah, so with pneumonitis, this is again something that we can see somewhat commonly with checkpoint inhibitor therapy, as we saw in this patient's case. But the grading is one, two, or three, mild, moderate, or severe, or severe is 3 to 4, and it's defined based

23:07

Speaker A

on the presence of symptoms, and also the degree in percentage of the parenchyma that's affected. Um so, with our patient, um this was uh this was a grade three, so we held immunotherapy.

23:21

Speaker A

She was admitted for IV methylprednisolone. We started her on 1 mg per kilogram per day. Um she also completed an infectious workup while in the hospital. Um again, sometimes if the pneumonitis is refractory to steroids, immunosuppressants may also be indicated

23:38

Speaker A

um in severe cases. So, you know, she did fine, and she continued to you know, we switched her to ABVD, and she's we just saw her actually uh last week, and she's doing really well on the steroid taper.

23:56

Speaker A

The other considerations in choice of front-line therapy are the cumulative anthracycline doses and breast cancer risk. To Up till now, we've all been taught that it's all radiation-related, and you know, you avoid radiation in young people because of mediastinal

24:09

Speaker A

exposure. There's a cardiac risk, but we're also learning now that anthracyclines by itself can also cause breast cancer, and I'll show you the data. We also don't know the safety of checkpoint inhibitors in someone with pre-existing autoimmune disorders, and

24:24

Speaker A

we don't know the long-term effects of the checkpoint inhibitors. Because remember, the solid tumors, it's used mainly in the uh the the largest body of experiences in the relapse refractory setting in a solid tumor, and you know, unlike

24:37

Speaker A

front-line Hodgkin's, where our patients are going to be cured and live for their normal lifespan, uh we don't know about late effects because most people with metastatic solid tumors, unfortunately, have a much shorter lifespan. Now, doxorubicin, there was a study from the

24:51

Speaker A

Netherlands showing that the uh at a very mature median follow-up of about 21 years, there was an increased breast cancer risk once you cross a cumulative dose of 200 mg per meter squared of Adriamycin, which was age independent.

25:07

Speaker A

It was not just in young females, it could have been any age, and it was with or without radiotherapy. Um this was really a new uh data emerging because we think of only radiation, we never think of the

25:19

Speaker A

anthracycline. But now we know that, and I bring this up because whether you're doing ABVD per rattle or you're doing Nivo AVD, all those have six cycles of AVD regimen, and that's 300 per meter squared of Adriamycin. Now, compared to

25:35

Speaker A

that, I think Brexanolone has a much lower dose, and I'll go over that in in in some other slide.

25:41

Speaker A

What about the risk of checkpoint inhibitors in patients with pre-existing autoimmune disease? Again, prospective data are lacking. The literature is from solid tumors, it's retrospective or meta-analysis, and practice is consequently guided by expert or consensus opinions.

25:56

Speaker A

We know that pre-existing AI increases the um rate of immune uh adverse events. There's earlier onset. It leads to discontinuation. They are of higher grade. And many of them had to discontinue checkpoint inhibitors or need high dose uh glucocorticoids.

26:13

Speaker A

So, the Society of uh Immunotherapy of Cancer came up with guidelines, which basically said that given the likelihood of an AI flare-up, clinical decision-making on the use of a checkpoint inhibitor for patients with existing autoimmunity should carefully weigh the severity and potential

26:30

Speaker A

consequences of AI disease exacerbation versus the potential benefits of treatment. So, how do we choose between Brexanolone and Nivo AVD? So, we know that Nivo AVD was basically only approved and tested in stage three or four. Uh Brexanolone

26:45

Speaker A

did include stage 2B based on uh presence of external sites of bulk, but that was in 16% of the patients. Nivo AVD is 6 months of therapy.

26:55

Speaker A

ABVD is shorter, it's 12 weeks if you are in term PET negative because all you get is four cycles. If you're PET positive, you get 18 weeks. There is much less acute hematologic toxicity with the Nivo AVD regimen

27:09

Speaker A

uh because it's not very myelosuppressive. And ABVD, it is more than uh much more than Nivo AVD, but much less than the prior escalated BEACOPP. And Charlene and I have used ABVD a fair amount and I think if you know how to use EPOCH, this

27:23

Speaker A

is a heck of a lot easier than using EPOCH. But you do need to work in a facility where you can check labs once a week and if you need, you know, to transfuse or uh support the patients,

27:33

Speaker A

you can. Uh In Nivo AVD in the trial, no GCSG was mandated in the arm or required, but the FDA label actually requires giving uh growth factors with Nivo AVD. And also, it can be given safely to patients over 60 if they the

27:49

Speaker A

answer is actually measurable, whereas ABVD is a little toxic in that patient population. Uh Nivo AVD excluded patients with pre-existing autoimmune disease, whereas uh uh uh that was not the issue with ABVD because there are no autoimmune side effects. It

28:06

Speaker A

it's Nivo AVD, uh there's no data on fertility as yet. Uh whereas in ABVD, we do have uh results with fertility showing that it is preserved.

28:16

Speaker A

So, moving on to our next case. This is a stage 2B uh patient. 27-year-old male presents to the emergency department with shortness of breath, dizziness, and drenching night sweats. PET CT shows this huge mediastinal mass, left supraclavicular, bilateral hilar

28:31

Speaker A

adenopathy. The mediastinal biopsy reveals classic Hodgkin's lymphoma, stage is 2BX, and this is a uh it's unfavorable by the EORTC and NCCN criteria shown as ESR, number of nodal sites, and mediastinal bulk. Now, baseline echo shows an LVEF of 48%. So,

28:49

Speaker A

borderline. So, this is the next uh polling question. How will you treat this patient? Is it ABVD per Rath, would you use Brexad, would you use BV AVD \* 4 + ISRT for the Breach trial, uh Nivo AVD \*

29:04

Speaker A

4 + ISRT for for the Nival trial, or would you just use uh Nivo AVD \* 6 for the Swag uh 1826 trial? So, please go ahead and uh vote.

29:16

Speaker A

We'll go over, you know, answers at the at the end of the presentation as to, you know, why certain choices make sense versus not or or may you know, it's a little nuanced, but uh let's see how this one plays out.

29:32

Speaker A

Okay. So, just about 10% would do ABVD per Rath, about a third would do Brexad, and you know, 14% BV AVD uh 22% Nivo AVD, and 17% uh uh would treat with six cycles of Nivo AVD. And so, it's kind of, you

29:52

Speaker A

know, all over the map except for the fewest answers choosing uh BV ABVD per Rath.

30:04

Speaker A

So, let's go over what the treatment choices for stage two unfavorable are. So, this is a little bit of a busy slide, but basically it's just talking about these unfavorable presentations.

30:15

Speaker A

And I think you we can start out with ABVD for two cycles or other regimens, and the other regimens are on the next slide. But, if you're starting out with ABVD for two cycles, and you do an interim PET, and if it's Deauville one,

30:29

Speaker A

two, or three, I think your biggest choices are you going to do chemotherapy alone, or are you going to do combined modality therapy? And combined modality therapy means an additional two cycles plus radiation per for EORTC trial, or

30:42

Speaker A

just continuing brentuximab and 10% of you chose this approach. The other uh regimen if you're I'm not going to go over if you're positive because then the therapy gets escalated. Uh the other regimens which can be used are combined

30:55

Speaker A

modality therapy, which is Nivo AVD uh with uh ISRT, that's four cycles of chemoradiation for the Nival, or BV AVD for the Breech, or Breech ad because I told you Breech ad had uh 17% with stage two disease.

31:16

Speaker A

So, we actually chose Breech ad because the ant- ejection fraction was just 48%. And uh patient was pretty symptomatic.

31:25

Speaker A

We didn't we really wanted to limit the amount of Adriamycin because we didn't know whether this would improve or not. So, after two cycles of Breech ad, he shows a complete metabolic response doubled two, so he's only going

31:36

Speaker A

to get two more cycles, so his cumulative adrio is going to be just 160. But, patient reports numbness in his fingertips that is making it difficult for him to button his shirt now.

31:47

Speaker A

So, Chandy, can you walk us through some unique toxicities of BV and how we manage them?

31:53

Speaker A

Yeah, so with brentuximab vedotin or BV, uh we know that it's an antibody uh drug conjugate um with anti-CD30 and delivering monomethylauristatin E um or MMAE, which is a payload that disrupts the microtubule network after binding to CD30 positive tumor cells or Hodgkin

32:15

Speaker A

cells. This mechanism can also affect the peripheral nerves, which include both myelinated and demyelinated fibers, which leads to neuropathy.

32:24

Speaker A

Some key factors in developing neuropathy include older age, pre-existing neuropathy due to diabetes or other factors, a higher cumulative dose exposure, and also use with other microtubule inhibitors.

32:38

Speaker A

Patients will commonly report numbness or tingling in the fingers or toes, weakness, or impaired fine motor skills like our patient did who was having trouble buttoning his shirt.

32:48

Speaker A

In HD21 or brentuximab vedotin about 39% of patients developed sensory neuropathy, while in Echelon 1 this increased to 65%, but encouragingly most patients either improve or had full resolution of their neuropathy within 1 to 2 years.

33:10

Speaker A

So, neuropathy is graded based on its interference with ADLs, which are either instrumental, which includes cognitive heavy activities such as managing finances or transportation, and self-care ADLs, which include tasks needed for basic survival, such as feeding or cleaning yourself.

33:30

Speaker A

In clinic when we're assessing for neuropathy, we'll often ask the patients to first describe the sensation. Is it burning? Is it painful? Is it numbness?

33:38

Speaker A

Is it tingling? And then assessing fine motor function, so asking them whether they can type or text well, if they can put on their jewelry, if they can tie their shoes, or button their shirts.

33:49

Speaker A

For grade 2 neuropathy, there are recommendations from the brentuximab package insert on holding the dose versus dose reducing for neuropathy to allow the nerves to heal on their own. And NCCN also has recommendations in their pain management guidelines for pharmacologic and

34:09

Speaker A

non-pharmacologic interventions if the neuropathy is painful. In addition to sensory motor neuropathy, neuropathy can also be autonomic. So, if a patient receiving brentuximab reports new symptoms such as erectile dysfunction, dizziness when standing too quickly, clinicians should be aware of

34:31

Speaker A

this potential effect. It's There's also a rare but serious side effect called inflammatory neuropathy, which is characterized by demyelinating symptoms and does require a neurology consultation and can respond to either IVIG or steroids.

34:53

Speaker A

Um so, after the second cycle, uh the brentuximab was held for our patient with cycle three and his neuropathy subsequently improved to grade one. So, then was added back at a dose reduction 1.2 mg per kilogram, whereas the

35:10

Speaker A

baseline dose was 1.8 mg per kilogram, and he continued with treatment with no further issues.

35:18

Speaker A

Um one more rare side effect of brentuximab is pancreatitis, which has really only been described in post-marketing data, but patients receiving brentuximab that present with upper abdominal pain, nausea, and vomiting, and who have additional risk factors for pancreatitis, such as male

35:34

Speaker A

sex or hyperlipidemia at baseline, should be suspected of developing pancreatitis and cross-sectional imaging should be considered if the amylase and lipase are elevated. These patients typically respond well to conservative treatment, and the FDA doesn't provide any guidance on rechallenging after

35:54

Speaker A

acute pancreatitis episode. So, we'll move on to our last case and we'll try to speed it up a little bit so that we have enough time for Q&A. This is a 42-year-old male treated with ABVD per RATHL uh for stage 3B uh with

36:11

Speaker A

splenic involvement. An interim PET he was negative over two, so we dropped the bleomycin, and he did very well, and the treatment PET was fine. Five months later, he comes to clinic, and we noted that he had a new left palpable

36:23

Speaker A

supraclavicular node, and a biopsy was consistent with classic Hodgkin lymphoma. PET demonstrated recurrence in the neck as well as in the mediastinum.

36:32

Speaker A

All his labs including ESR were normal. So now the standard of care is using a second-line regimen and taking the patient to auto transplant. And with the in with the uh advent of novel agents, instead of using chemotherapy alone, it's moved to using

36:49

Speaker A

a checkpoint inhibitor or brentuximab vedotin in combination with chemotherapy or just two novel agents by their own with significantly higher progression-free survival rates than we've seen with just chemo alone.

37:02

Speaker A

And you can see that even choosing between brentuximab or a checkpoint inhibitor, the checkpoint inhibitor base combinations pre-auto transplant are associated with significant improvement in outcomes in Hodgkin's lymphoma. And this is just a nice recent a retrospective review which uh of

37:21

Speaker A

a you know, multi-center trial which showed that if you get a checkpoint inhibitor during salvage, the outcomes are much better than using chemotherapy alone or using a brentuximab base regimen.

37:33

Speaker A

So there's a practical approach and one of my junior colleagues and I had written this review about a year ago. If somebody um presents to you who has primary refractory disease where you know, after six cycles of frontline therapy they

37:46

Speaker A

have progressed or they relapse within 3 months. Of course, if they've had a frontline nivo-AVD, then you're going to use a BV base salvage with or without chemotherapy. If they've had a frontline BV regimen, you'll use a checkpoint

37:58

Speaker A

regimen. But if they haven't had either, if they've been treated just with ABVD, we would prefer a checkpoint base regimen. If they relapse more than 3 months, I think the challenging of the frontline regimen with a checkpoint inhibitor is always the preferred

38:12

Speaker A

approach. And if they don't respond, then you can switch to BV. The idea is to get them into a CR and take them to transplant.

38:21

Speaker A

So we start our patient with BV-nivo 2 weeks after therapy he to the ER with new frontal headache, retro orbital headache, neck and shoulder stiffness and one episode of fever. So, in the ER he has a MRI which show of the head and

38:34

Speaker A

spine with no changes. Blood cultures are negative and other labs are completely normal. So, uh uh Channing, can you just take a look quickly and tell us how we worked this up?

38:44

Speaker A

Yeah, so this patient went into the emergency room and had a lumbar puncture done. And as you can see here, the WBC count as well as the lymphocytes were elevated while the rest of the infectious workup including a meningitis

38:56

Speaker A

panel and HSP were all negative. So, I'll talk a little bit about some rare complications of checkpoint inhibitor therapy and neurologic complications. In general, patients that are treated with CPIs neurologic IRAEs are pretty rare and generally occur about less than 1% of the time.

39:17

Speaker A

Specifically with nivolumab, neurologic events occurred in less than 3% of the cases. However, they were often grade 3 to 4 in severity and had a relatively high mortality rate.

39:28

Speaker A

Some of the other rare side effects mentioned here in this table are hypophysitis we talked about earlier, type 1 diabetes and myocarditis which does have the highest mortality rate of all IRAEs.

39:40

Speaker A

Looking at neurologic complications specifically, myositis is the most common followed by neuropathy and myasthenic syndromes. Meningitis is pretty rare but also has a lower rate as opposed to myasthenic syndromes and encephalitis which can be pretty serious.

39:58

Speaker A

So, with meningitis patients can present with fever, light sensitivity, neck pain and nausea and vomiting like our patient did. Although, their mental status will be normal and an initial workup should include brain imaging with a pituitary protocol to rule out hypophysitis as

40:13

Speaker A

well as a lumbar puncture to rule out other um etiologies. And in patient care for these patients will also include antimicrobial coverage as well as steroids.

40:24

Speaker A

With encephalitis, the patient will present with altered mental status, and autoimmune testing should be added to the CSF labs.

40:32

Speaker A

If symptoms progress for 24 hours after initiation of steroids, then IVIG or plasmapheresis, um, should be considered.

40:41

Speaker A

So, this is myositis, which is another very rare complication. And this this is a case and another case we managed of a 31-year-old female who got a BV nevo for as two novel agents in combination for a salvage second-line therapy before

40:55

Speaker A

transplant. And 3 weeks later, she presented with a bilateral forearm soreness for 6 days. On exam, this was firm and tender to touch, and her, uh, CK level was more than 11,000. And she was admitted for IV steroids. You can

41:09

Speaker A

see her MRI, and her EMG done was compatible with myopathy and neuropathy without a neuromuscular junction. So, again, very rare, but a serious complication which requires a low index of suspicion and doing the right tests.

41:22

Speaker A

So, Channing, can you just talk to us a little bit about more of this?

41:26

Speaker A

Yeah, so again, myositis is another rare, but potentially serious toxicity, um, and again, this case from our clinic a few years ago, um, showed that the patient's CK level was very elevated.

41:39

Speaker A

Um, so, she had severe myositis based on the grading here, where CK level greater than 1,000, um, automatically makes them a a grade two or three or higher.

41:50

Speaker A

Um, the effects can be pretty serious, um, if the cardiac muscles or the muscles used for breathing and swallowing are affected. And in severe cases for management disease-modifying drugs like methotrexate or mycophenolate can be used for treatment.

42:08

Speaker A

Inflammatory arthritis, um, just quickly is another musculoskeletal side effect from um, checkpoint inhibitor therapy that if it's refractory to steroids it may use require the use of DMARDs, IL-6 inhibitors such as tocilizumab or TNF inhibitors and rheumatology should be

42:25

Speaker A

consulted early and immuno immunotherapy should always be held for grade three. Lastly, I'll talk quickly about myocarditis. This is one of the most deadly checkpoint inhibitor toxicities and if it occurs immunotherapy is always discontinued regardless of the grade.

42:44

Speaker A

Myocarditis can co-occur with myasthenia gravis or myasthenia gravis-like syndrome as well as myositis. So it's important to include non-cardiac biomarkers in the workup as well.

42:55

Speaker A

And myocarditis should always be ruled out if pericarditis is is suspected, but if pericarditis is the case that can be managed per usual recommendations as opposed to patients with suspected myocarditis who are admitted started on high-dose steroids and and

43:12

Speaker A

then with immunosuppression added if there's no improvement after 48 hours on steroids. So we often hold immunotherapy when adverse effects occur, but when to rechallenge depends on the type and grade of the event. So in general endocrine side effects don't usually

43:28

Speaker A

require discontinuation as long as hormone replacement being managed. Recurrence of the same toxicity following a rechallenge requires permanent discontinuation and a rechallenge may not be necessary if the patient has already had an acceptable response.

43:43

Speaker A

And for specific toxicities the grade any grade of demyelinating disease requires permanent discontinuation and rechallenging is contraindicated in this case. Myocarditis greater than a grade two requires permanent discontinuation and the rest of the toxicities occurring at either grade three or four or grade

44:01

Speaker A

four severity will require permanent discontinuation and the patient will not be eligible for rechallenge in these cases.

44:11

Speaker A

So, it's really important also to do long-term follow-up because again, we don't know what the long-term consequences are and the exact incidence. And in general from the solid tumor world, we know that endocrinopathies arthritis xerostomia and neurotoxicities are killer events

44:26

Speaker A

are more likely to become chronic toxicities. And these will impact survivorship as these patients are going to live for a long time. And I think it's really important to measure this as part of clinical trials and not just

44:38

Speaker A

during treatment. So, in conclusion, there's been a paradigm shift in the management of advanced classic Hodgkin. Checkpoint inhibitor or BV-based regimens now have progression-free survivals of over more than 90%. They have unique toxicities which are important to recognize, act

44:55

Speaker A

promptly on, and seek help if you have a local IO team which is working on this or from a send your patient to a or call a referral center for help. It's also the importance of following our patients.

45:07

Speaker A

At relapse, the standard of care is still a second-line regimen and transplant is of course going to be more challenging now that checkpoint inhibitors and brentuximab are used in front-line, but the standard still stays. And as I showed you, using a

45:19

Speaker A

checkpoint inhibitor-based salvage has better outcomes than uh regimens without that. So, just to quickly go over, you know, the options for these uh questions, the two polling questions. The first was the uh the 34-year-old with stage four disease as to what the options were.

45:36

Speaker A

Many of you chose ABVD per ratel. It's fine if you're practicing in an area where you don't have access to novel agents. Uh that certainly would be a standard of care. Uh otherwise, I think in the United States,

45:49

Speaker A

it's going to be either uh series. Actually, both of those regimens, depending on the scenario, are category one in the NCCN guidelines.

45:59

Speaker A

For the second case, the 27-year-old male with the bulky stage Hodgkin's with uh ejection fraction of 48%.

46:07

Speaker A

Which of the regimens is more apt for this? Again, if you are practicing in an area where you don't have access to a novel agent, then ABVD per protocol is fine. We chose BRECADD for two reasons. One is because the

46:22

Speaker A

anthracycline exposure is lower, and it has an excellent long-term follow-up of 5 years and a cure rate of 95%.

46:30

Speaker A

The extent of the mass is pretty big. It's a very big mediastinal mass that goes in all the way from the top to the bottom of the chest. The the radiation field is going to be massive. So, we

46:40

Speaker A

would try to avoid any of regimen, whether it's Nivo AVD or BV AVD, which includes radiation. And, you know, some of about 20% chose Nivo AVD \* 6. That was not the SWOG 1826 trial. That restricted it to stage three or four,

46:56

Speaker A

and it's approved in the United States only for stage three and four disease, not for stage two bulky disease. That may change in time, but for now, it's not. And that is the last slide, and thank you for your attention, and we

47:08

Speaker A

will go through questions. I see two questions on the chat already, and we hope more will come as we go along. The first one is maybe Chandni, you can answer this. What cardiac labs do you order for immune-related

47:25

Speaker A

side effect monitoring? Do you order a baseline, or do you order only when they get symptoms, and if so, what do you order?

47:32

Speaker A

Yeah, so prior to each cycle, including immunotherapy, we order a high-sensitivity troponin, and that's actually built into our chemotherapy orders. So, that is something that's checked prior to every cycle.

47:46

Speaker A

And if it gets high, we have a cardiology referral or reach out to the IO toxicity team, right?

47:54

Speaker A

Yeah, we have a very low threshold to reach out to our cardiology colleagues in this case.

48:00

Speaker A

Okay. The next question is with Nivo, do you see adrenal insufficiency? And is cortisol or ACTH reviewed in certain patients? So kind of do we check a cortisol at baseline or ACTH at baseline? And I mean if someone presents with

48:19

Speaker A

hypertension, yes we will check it, but what do we do at baseline and how do we monitor this?

48:23

Speaker A

Yeah, so as part of the standard baseline labs, we do check an ACTH. And again, like high sensitivity troponin, this is something that's built into our um cycle every cycle pre-treatment lab panel.

48:41

Speaker A

So you know, while we're waiting for more questions to come in, uh at the practical level, uh generally when we see somebody with just say a TSH elevation because we're checking uh we check it at baseline and we're

48:53

Speaker A

checking it with Do you check it with every cycle or do you check it with every alternate cycle?

48:57

Speaker A

So it's checked with every cycle. Okay. And if it's And if it's high, but the T3 T4 is okay, but the TSH is less than 10, if I understood you correctly, we just follow the patient.

49:08

Speaker A

Yeah, so if the TSH is less than 10 and the patient is feeling okay, then we just follow them.

49:16

Speaker A

Okay. And if it is And if it's high, what dose of uh the dosing?

49:24

Speaker A

Yeah, so typically for for levothyroxine dosing, it's weight-based dosing um and we usually start at a lower dose depending on the patient's age and titrate it up.

49:36

Speaker A

Um so for instance, for our patient that presented with hypothyroidism, um we they were younger, so we started them on 100 micrograms of levothyroxine daily.

49:48

Speaker A

And then we check it with every cycle and titrate as needed. Mhm. So in about, you know, 20-30% of the patients uh they are stuck with the hypothyroidism and need to be on this for life. So, when you are doing

50:01

Speaker A

your survivorship visit in general, apart what do you Firstly, when do you do the survivorship visit and what are the key elements which people should be aware of in the in your survivorship plan?

50:15

Speaker A

Yeah, so at our institution we typically like to see patients for their first survivorship visit about 3 months after their end of treatment visit. So, we at that point review their survivorship plan, whether or not they'll need additional cardiac surveillance based on

50:30

Speaker A

their cumulative anthracycline dose, whether or not they have any immune-related toxicities such as hypothyroidism that will need to be followed long-term. And we also talk about bone health particularly in postmenopausal women that may have had exposure to high-dose steroids as part

50:46

Speaker A

of their regimen. So, these are all components that are included in the survivorship care plan that I provide.

50:54

Speaker A

Thank you. So, one question which has come through the chat is would you repeat the doxorubicin cumulative dose in a patient who would have had four cycles of ABVD?

51:06

Speaker A

I'm not quite sure I understand the question, but I think we've seen that at four of ABVD you're at 200 per meter squared. So, if there is something if somebody has has advanced disease and you're choosing the ABVD, there is no

51:20

Speaker A

data with less than six cycles, so you would finish it. We would you know check an echo as Shanley mentioned as part of survivorship, not after four cycles if they started out with a normal echo. If they have early stage disease, you can

51:33

Speaker A

abbreviate that therapy and add radiation, but make sure that the radiation field is okay.

51:39

Speaker A

Uh the other I think it's more of a comment. There is a trend of avoiding radiotherapy, Nevertheless, it's has been proven benefit. It is not administered up front, but later when the field becomes smaller, dose reduction is allowed, and

51:55

Speaker A

technical aspects are highly improved. So, we agree, and that's why you can see that combined modality therapy is still very much part of the NCCN guidelines, especially in early stage favorable disease where patients with just two cycles of ABVD and ISRT of 20 gray,

52:11

Speaker A

which is a very low dose, have very good long-term outcomes. So, it's it is they may be a trend, but I think as an in experienced centers, and especially with the data showing a superior you know, mild benefit a modest

52:25

Speaker A

progression-free survival benefit, it's very much part of the regimen. So, that's why I started out by saying the choice you have to make is are you going to use a combined modality approach, or are you going to use a chemotherapy

52:37

Speaker A

um alone approach? And we I would suggest every patient be seen jointly in a tumor tumor board where a radiation therapist is engaged in the conversation. So, you can see whether the field is safe or not, and then make

52:49

Speaker A

the decision. If you have a young female with axillary involvement, you will avoid radiotherapy because of the breast cancer risk. But otherwise, I you know, for the right patient, it's definitely a very uh it's totally fine.

53:02

Speaker A

Uh one question, Channing, do you order cortisol uh A1C labs if no symptoms, and what frequency?

53:10

Speaker A

Yeah, so as I mentioned, we check ACTH prior to each checkpoint inhibitor cycle. Okay.

53:19

Speaker A

Uh what are the thoughts of adding an agent like propranolol for symptomatic treatment with hyperthyroidism prior to seeing the hypothyroidism due to checkpoint toxicity? I think they can present with either, and they mostly present with hypo. And if they

53:36

Speaker A

present with frank hyper, then we, you know, do the propranolol and everything, but not otherwise if it's because the more common one is hypo.

53:45

Speaker A

Uh the next question is experience with pembro in terms of outcome compared to nevo. So, the only randomized trial was the SWOG trial which I showed you, the 1826.

53:55

Speaker A

Pembro has been checked and the results look just as good. You know, pembro AVD has been checked, pembro nevo AVD, but they're all smaller phase two trials.

54:05

Speaker A

The only one which has gone to a randomized trial was the nevo AVD. I think they're pretty comparable drugs.

54:10

Speaker A

In the relapse setting, you know, there's more data with pembro, especially the pembro G&D regimen has a very high CR rate of like 94% after just two cycles. So, you can take the patient quickly to transplant. When pembro was

54:24

Speaker A

compared to BV as single agent in the keynote 204 study, pembro was better than BV and showed a survival advantage.

54:32

Speaker A

But again, I think pembro versus nevo overall, we tend to think of pretty much equivalent rather than you know, different.

54:42

Speaker A

I think if you failed one, there's no advantage the other one. Another question, have you seen any AYA patients who have developed a rare sensory motor myopathy and then a grand mal seizure?

54:56

Speaker A

So, we you know, our patient was 30 something and had myositis, but that's sort of the extreme which we initially thought she had neuropathy when she called us and said my arms feel weak. But we haven't really known the I

55:11

Speaker A

haven't seen anyone with a seizure. I'm sure it can happen when you have a you know, especially if they have bad encephalopathy or a meningitis like picture. I'll tell you, have you any of our colleagues told us about any

55:23

Speaker A

seizure? So, we haven't, but that doesn't mean it doesn't happen. And I think Ancesion has sent a message that this will be the last questions because we have to stay within time.

55:34

Speaker A

Thank you all for joining and we appreciate your engagement. Take care. Thank you.

Topics: Hodgkin lymphoma brentuximab vedotin nivolumab checkpoint inhibitors ECHELON-1 SWOG 1826 HD21 RATHL immune-related adverse events NCCN

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