Classic Hodgkin Lymphoma - JAMA Clinical Reviews

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[00:03]
A
Hi, I'm Derek Angus, a senior Editor at JAMA and host of Healthy Dialogue, a new podcast from the JAMA Network. Join me as we go beyond the latest discoveries with nuanced, in depth conversations with the world's leading experts to explore the most pressing issues in health and healthcare, from trends in autism diagnosis to private equity acquisition to AI and much, much more. Visit JAMA networkaudio.com or search Healthy Dialogue wherever you get your podcast to subscribe.
[00:46]
B
From the JAMA Network. This is JAMA clinical reviews, interviews and ideas about innovations in medicine, science and clinical practice.
[00:55]
C
Hello and welcome to our listeners around the world. I'm Dr. Kristin Walter, Deputy Editor at JAMA. I'm joined today by Dr. Allison Moskowitz, Associate Attending Lymphoma Service, Memorial Sloan Kettering Cancer center in New York, New York. Today we will be discussing a JAMA article that she co authored with Dr. Kishan Patel titled Classic Hodgkin Lymphoma A Review. This article was published online in Jama on August 3rd and there's a link to the article in the episode description. Dr. Moskowitz, thank you so much for joining us on this podcast.
[01:30]
B
Thank you so much. It's great to be here.
[01:32]
C
Before we start, I wanted to acknowledge that although Classic Hodgkin's lymphoma is the full name of this disease, I'll be using the term Hodgkin's lymphoma during this podcast to start off. Your article states that Hodgkin's lymphoma, which is a lymphoid malignancy derived from B cells, was diagnosed in about 82,000 people worldwide in 2022 and about 88,700 people in the US in 2025. What is the typical age of diagnosis of Hodgkin's lymphoma?
[02:01]
B
The majority of the patients that we see with Hodgkin lymphoma tend to be young. The median age is in the 20s, although there is a bimodal distribution where we see a group of patients who are in their 20s to 30s. But then we also see a group of patients who are over 60 as well, but they tend to be the less frequent patients that we see with this disease.
[02:24]
C
And what are some known risk factors for Hodgkin lymphoma?
[02:28]
B
I would say that the majority of patients who come to us with a new diagnosis of Hodgkin lymphoma, generally we don't know why they developed it and so that is more the typical scenario. There are certain risk factors that have been identified, such as having immune deficiency. There is a higher rate of Hodgkin lymphoma in patients who have a family history, but generally I would say for the majority of patients, we don't know why they develop it.
[02:56]
C
And is there a familial predisposition for Hodgkin's lymphoma?
[03:01]
B
Yes. So there is a familial predisposition for Hodgkin lymphoma. There are higher risks among siblings and particularly higher risks among twins. And so that has been reported. Sometimes we see multiple people within the same family developing it. These are rare situations, but we do see it.
[03:22]
C
And can you also discuss Epstein Barr virus and the link with Hodgkin's lymphoma?
[03:27]
B
The Epstein Barr virus or the virus that causes mono is positive in 90% of the population, but there is a link between the virus and Hodgkin lymphoma. I'd say that in Hodgkin lymphoma itself, about 40% of the cases of Hodgkin lymphoma are positive for the EBV virus and seem to be very closely linked to the development of the disease in those patients. Why certain patients end up developing EBV related Hodgkin lymphoma, we don't always know. It does tend to be more commonly seen in patients who have immune deficiency, and we also see it more commonly in older patients with Hodgkin lymphoma.
[04:07]
C
And your article discusses how the diagnosis is typically based on an excisional lymph node biopsy that reveals Reed Sternberg cells in a polymorphous inflammatory infiltrate and that the 2022 World Health Organization classification system includes four histologic subtypes, which are nodular sclerosis, mixed cellularity, lymphocyte rich and lymphocyte depleted. Which of these subtypes is most common in the US and is there geographic variability in subtype frequency?
[04:39]
B
In the US the most common subtype is nodular sclerosing subtype. We see that more commonly in the younger patients who develop Hochulmphoma and as well as patients with an int immune system. The other subtypes, such as mixellularity or lymphocyte deplete we tend to see in areas with reduced resources and also the mixellarity we tend to see in older patients.
[05:05]
C
And what is the typical presentation of patients with Hodgkin lymphoma?
[05:09]
B
I'd say the most common presentation is potentially a lump in the neck that someone palpates, often they may come to the attention of their primary doctor. And this enlarged lymphadenopathy may be considered to be potentially an infection. And they may first get a course of antibiotics, but then typically the lump will persist and that will lead to a biopsy.
[05:33]
C
And how often is it incidentally found on imaging?
[05:37]
B
It's not typical that Hodgkin lymphoma is found incidentally on imaging because it usually grows on the faster side. So usually it comes to someone's attention either through a lump in the neck or. Or through potentially symptoms from a mass in the chest, which could be cough or shortness of breath. Many patients will have B symptoms such as fevers or night sweats. Some patients will have pruritus that sometimes can be very debilitating or last for quite a long time before the diagnosis is made. So all of these things can be very nonspecific. But one of these symptoms tends to lead to the diagnosis.
[06:16]
C
And your article also mentions alcohol associated pain that's highly specific for the diagnosis. Can you describe this symptom and how frequently does this occur?
[06:27]
B
This is one of those classic symptoms that we think about with Hodgkin lymphoma, but it's really rare that we see it. So it's pretty unusual. But what it is is that basically someone will have pain in their area of lymphoma upon drinking alcohol. And sometimes someone will have the story of every time they drink alcohol, they have pain in their neck or in their back or in their chest. And so as a result, they stopped drinking alcohol. And sometimes that can be months before they even have the diagnosis of Hodgkin lymphoma. But it is one of those textbook symptoms that people get, but we see it quite rarely.
[07:02]
C
And you briefly mentioned the concept of B symptoms. Can you describe what these symptoms are and approximately how many of patients have B symptoms and what is their significance in terms of staging?
[07:15]
B
There are really three parts to the B symptoms. There's night sweats. And really what we're thinking about with night sweats, it's drenching night sweats, where someone needs to change their clothes or change their sheets in the middle of the night because of the sweats. Fevers are another one. And then weight loss, which is typically defined as losing 10% of your weight. And so having bee symptoms is considered to be one of the risk factors within patients who have early stage disease. So with early stage disease, we tend to categorize patients as either being in the favorable group or an unfavorable group. And one of those factors that has someone meet criteria for having unfavorable Hodgkin lymphoma is having B symptoms. For advanced stage disease, having B symptoms isn't considered to be one of the risk factors. And as far as how many people have B symptoms, it's about 30 to 40% of people with Hodgkin lymphoma.
[08:12]
C
And you've mentioned early stage disease, which includes stage one and stage two, and that it's risk stratified based on the presence of favorable or unfavorable features. In addition to the B symptoms. What are some other unfavorable features?
[08:26]
B
Another unfavorable feature is having a bulky mediastinal mass. Classically, that's defined as having a mass that measures 10 centimeters or more. Another one is having extension into extranodal sites of disease. So an extranodal site means it's outside of the lymph node system. And although generally we think of someone who has extranodal sites of disease as having stage four disease, they can have an extranodal site. Even with early stage disease, it just means that the disease is growing into an organ, such as a lymph node in the chest growing into the lung. So it's direct extension as opposed to a distant area. And then finally, it's also the number of lymph node sites. So having more than three separate lymph node sites is considered a risk factor as well.
[09:15]
C
And moving on to treatment, how is early stage Hodgkin's lymphoma treated?
[09:20]
B
The standard of care is to give chemotherapy and potentially with or without radiation therapy. And the amount of treatment that we give does depend upon whether someone is considered to have favorable or unfavorable disease. Now, I hate the terms favorable or unfavorable, because the cure rate for both favorable and unfavorable disease is very high. But the reason why we use these distinctions is that we can get away with less treatment for patients who are considered to have favorable disease. So fewer cycles of chemotherapy, a better chance of avoiding radiation. Whereas for patients who have what we consider to be unfavorable disease, we do tend to give increased number of cycles of treatment.
[10:03]
C
And how is advanced stage Hodgkin lymphoma treated?
[10:07]
B
The treatment for advanced stage disease has gotten quite simple recently. We always use chemotherapy, and now it's in combination with a drug called nivolumab, a drug that targets PD1. So the most common regimen that's given in the US is nivolumab, plus three different chemotherapy drugs called adriamycin, vinblastine and dacarbazine. So we call the regimen NIVoAVD. And the standard course of treatment is to give six months of treatment, which includes 12 treatments. And this is now the standard of care, based upon a study that was published about a year and a half ago, which was called the S 1826 Study, which was a study for patients who had stage three or stage four disease and they were randomized to either receive this nivo plus AVD regimen versus the older standard of care, which was brantuximab vedotin plus avd. So this nivo plus AVD regimen is now the standard of care.
[11:06]
C
Your article also discusses relapsed or refractory Hodgkin lymphoma. What percent of patients experience these conditions and how soon does this usually occur after diagnosis?
[11:18]
B
So the chance of having relapse or refractory disease has become lower and lower over time because the treatments in the frontline setting have gotten better. So for a patient who has early stage disease, the chance is about 10% or less. And then for patients who have advanced stage disease is also less than 10%, based upon the data from the most recent studies that have incorporated the novel agents such as nivolumab or Brentuximab. And as far as the timing of relapse, generally it's close to the timing of completion of treatment. So we tend to see it's most commonly within the first year and then potentially in the second year after completing treatment and becomes exceedingly uncommon beyond two years after completing treatment.
[12:06]
C
And what is the treatment for relapsed or refractory Hodgkin's lymphoma?
[12:10]
B
The standard of care for relapsed refractory Hodgkin lymphoma is to receive an additional regimen that is different from the frontline treatment. And there are several different options available. And then the goal of that treatment is to achieve a complete response on PET imaging. Once the patient achieves remission with their second line treatment, we then consolidate the treatment with an autologous stem cell transplant.
[12:39]
C
And when are patients treated with an allogeneic stem cell transplant?
[12:44]
B
So it's rare that we're using allogeneic stem cell transplant for Hodgkin lymphoma. And the reason is that the cure rate for Hodgkin lymphoma is quite high after frontline treatment. And then for the patients who are not cured with frontline Treatment, we do have a very good chance of curing them in the second line setting as well with an autologous stem cell transplant. And once it was determined that drugs targeting PD1, such as nivolumab and pembrolizumab, are highly effective in Hodgkin lymphoma, we learned that we can actually control the disease quite well for people who have relapse or refractory disease. And that led us to delay use of an allogeneic stem cell transplant because the allogeneic stem cell transplant has risks associated with it. There is a chance of graft versus host disease. There's a chance of even mortality as high as 10 to 15% with the treatment. So I'd say that we are very hesitant to use it in our patients. Although that all being said, we're now seeing that the efficacy has improved recently with as many as 50% or more patients achieving long term REM, and that's probably the result of them being exposed to PD1 blocking agents. And so getting back to your question of how often do we use it? So it's quite rare, I guess the situations where we might use it is for patients who have progressed or are no longer able to tolerate the best drugs that we have for Hodgkin lymphoma, which are the drugs that target PD1, as well as Brituximab, vedotin.
[14:18]
C
And moving on to prognosis, how often is cure achieved?
[14:22]
B
Over 90% of patients are cured either through their frontline treatment or through the second line treatment. And so the majority of the patients will go on to recover from treatment and to live fairly normal lives, thankfully.
[14:38]
C
And after treatment for Hodgkin lymphoma, survivors have an increased risk of secondary malignancies, cardiopulmonary dysfunction, and thyroid dysfunction. Can you discuss this? And which cancers are most common among these patients?
[14:51]
B
With regard to start with thyroid dysfunction, we do see thyroid dysfunction for patients who have been exposed to PD1 blocking agents. And then also there's a risk of thyroid dysfunction as well as thyroid cancer for patients who received radiation to their neck. And so this is something that we monitor for thyroid dysfunction. And then as far as monitoring for secondary malignancies in that setting, we tend to do through physical examination. For cardiovascular disease, there is a risk of cardiomyopathy related to anthracycline, as patients will receive up to 300 milligrams per meter squared of adriamycin with their initial treatment. And so this is monitored with an echocardiogram that's done within a year of completing treatment and then repeated later on if they develop any worrisome symptoms. As far as secondary malignancies, there is a higher risk of malignancies, potentially GI malignancies, and the risk of secondary leukemia related to chemotherapy. So with regard to the risk of leukemia, the monitoring is just through follow up and monitoring, routine blood work. And with regard to GI malignancies, there's not a specific follow up, but it's more having a high index of suspicion and referring a patient for evaluation if they're having any GI related symptoms. And then finally there's a risk of breast cancer for patients who received radiation to their chest. And the monitoring for that is to begin monitoring earlier than we would for the general population. And it's generally recommended that we start that monitoring about eight years after radiation or sooner if they're at the age where they would get routine monitoring. And then we tend to use more intense monitoring where we alternate with mammogram and ultrasound as well as breast MRI on a every six month basis.
[16:50]
C
And your article discusses how de escalation of therapy has become a focus of study to minimize treatment related morbidity. Can you discuss this?
[16:59]
B
Yeah. So we are generally using this particularly for patients with early stage disease. And we right now are using an interim PET response to decide whether or not we could potentially give patients fewer cycles of chemotherapy and also avoid radiation therapy because many of these later side effects of treatment are related to radiation therapy. And also many of them are related to the number of cycles of treatment that patients receive. So for early stage disease, there are several studies that have shown that patients who have a negative PET scan, meaning a PET scan that shows normalization or no evidence of active disease after two cycles of treatment, can often get away with a shortened course of chemotherapy and no radiation therapy. And we tend to use treatment paradigms like that more commonly in patients who are younger, where the late risks of radiation can be more significant because they have many, many more decades of life ahead of them. And so that's what we've been now using for patients with early stage disease. For older patients, the risks of radiation are really minimal. And so as a result, we often will use our older approaches where we use combined modality therapy, meaning chemotherapy followed by radiation therapy for advanced stage disease. Right now we're generally not using response adapted therapy, at least in the US where we're using the nivolumab plus AVD regimen. But that may change as there's studies that are looking to see if we can use cell free DNA or circulating tumor DNA to modify therapy and potentially allow patients receive less treatment. The regimen that is used more commonly in Europe and particularly in Germany, which is the Bricad regimen which was developed by the German Hodgkin Study Group. This is a regimen that is pet guided. So patients initially receive two cycles of treatment and if their pet is normal after the two cycles they receive just a total of four cycles. If their pet remains positive after two cycles then they receive a total of six cycles. So there are risk adapted approaches that are used with some of the regimens for advanced stage disease before closing Is
[19:20]
C
there anything we didn't discuss in this podcast that you'd like to mention?
[19:24]
B
I would like to mention fertility preservation because this is something that is very, very important. I would say for every young individual who has newly diagnosed Hodgkin lymphoma, many of our treatments that we use for newly diagnosed disease such as abvd, actually has a very low risk of causing infertility. But that being said, even young patients receiving ABVD or Nivolumab plus abd, even though they may regain their fertility after completing the treatment, they do have a shortened lifespan of fertility with any of these treatments and so they may go into menopause earlier than they would have had they not received the treatment. That's one reason why I often encourage fertility preservation before starting treatment. And the same goes for men. I think it's very important for them to undergo fertility preservation as well. And the second reason is that I see it as almost an insurance policy because although we mentioned that the majority of patients will be cured with their frontline treatment, there's still patients who are not cured, and some of those patients need to go right into additional therapy. And that additional therapy, as we mentioned, may include an autologous stem cell transplant, which has a much higher chance of causing infertility. And because of that, it's better to take care of the fertility preservation before anything starts so that we don't have to worry about how the treatment's going to impact fertility further down the road.
[20:59]
C
Thank you so much for sharing your thoughts with us about this interesting and important topic.
[21:04]
B
Thank you so much. It was great to talk with you.
[21:07]
C
I'm Dr. Kristen Walter and I've been speaking with Dr. Allison Moskowitz from Memorial Sloan Kettering Cancer center in New York. You can find a link to this JAMA review article that we discussed in this episode's description. This episode was produced by Daniel Musisi at the JAMA Network to follow this and other JAMA Network podcasts, please visit us online@jamanetworkaudio.com or or search for JAMA Network wherever you get your podcasts. Thanks for listening.
[21:36]
B
This content is protected by copyright by the American Medical association with all rights reserved, including those for text and data mining, AI training and similar technologies.

Summary5 min read

JAMA Clinical Reviews — Classic Hodgkin Lymphoma

Host: Dr. Kristen Walter, Deputy Editor at JAMA
Guest: Dr. Allison Moskowitz, Associate Attending, Lymphoma Service, Memorial Sloan Kettering Cancer Center
Publication Date: August 3, 2026
Episode Focus: An in-depth review of classic Hodgkin lymphoma based on the recent JAMA article co-authored by Dr. Moskowitz and Dr. Kishan Patel.

Episode Overview

This episode provides a comprehensive, clinically-focused overview of classic Hodgkin lymphoma, guided by leading lymphoma specialist Dr. Allison Moskowitz. The discussion centers on epidemiology, risk factors, histologic subtypes, clinical presentation, diagnostic processes, treatment approaches, survivorship, and evolving strategies aimed at minimizing treatment-related toxicity.

Key Discussion Points & Insights

Epidemiology and Risk Factors

Incidence & Demographics
- In 2022, about 82,000 cases worldwide; 8,700 in the US in 2025.
- Bimodal age distribution: Most commonly diagnosed in the 20s-30s, but also seen in patients over 60.
  
  "The median age is in the 20s, although there is a bimodal distribution..." — Dr. Moskowitz [02:01]
Risk Factors
- Unknown cause for most patients; some higher risk with immunodeficiency or family history.
- Familial predisposition is rare but documented, highest among siblings/twins.
- Epstein-Barr Virus (EBV) is linked to ~40% of cases, more prevalent in older or immunodeficient patients.

Pathology and Diagnosis

Diagnostic Method
- Excisional lymph node biopsy revealing Reed-Sternberg cells within a polymorphous inflammatory infiltrate is standard. [04:07]
- WHO 2022 Classification: 4 subtypes — nodular sclerosis (most common in US), mixed cellularity, lymphocyte rich, lymphocyte depleted.
  
  "In the US, the most common subtype is nodular sclerosing subtype." — Dr. Moskowitz [04:38]

Clinical Presentation

Most Common Symptoms
- Palpable neck lump/lymphadenopathy often mistaken for infection
- 'B symptoms': Drenching night sweats, fevers, >10% weight loss over 6 months
- Pruritus; cough or shortness of breath if mediastinal mass present
- Rare: Alcohol-induced pain at lymphoma sites
  
  "It's really rare that we see it ... someone will have pain in their area of lymphoma upon drinking alcohol." — Dr. Moskowitz [06:26]
Incidental Discovery
- Uncommon; disease typically presents via symptoms due to its more rapid growth.
B Symptoms & Staging
- B symptoms present in 30-40% of cases — a marker of unfavorable risk in early stage disease, but not significant for advanced stage classification.

Staging and Risk Stratification

Staging
- Early (Stage I-II) vs. Advanced (Stage III-IV)
Unfavorable Risk Features (Early-Stage)
- Bulky mediastinal mass (≥10cm)
- Extranodal extension (direct organ invasion)
- Involvement of >3 lymph node regions

Treatment Approaches

Early-Stage Disease
- Combination chemotherapy (with or without radiation), tailored by risk features.
  
  "We can get away with less treatment for patients who are considered to have favorable disease." — Dr. Moskowitz [09:19]
Advanced-Stage Disease
- Standard regimen is nivolumab (PD-1 inhibitor) + AVD (adriamycin, vinblastine, dacarbazine), based on findings from the S1826 study.
  
  "This nivo plus AVD regimen is now the standard of care." — Dr. Moskowitz [10:06]
- Six months/12 treatments.
Relapsed/Refractory Disease
- Occurs in <10% of cases with modern frontline treatment.
- Additional (different) chemotherapy, with the goal of complete response on PET scan, followed by autologous stem cell transplant.
  
  "Once the patient achieves remission... we then consolidate the treatment with an autologous stem cell transplant." [12:10]
- Allogeneic transplant is rare, reserved for multi-refractory cases, due to higher risk.

Prognosis & Survivorship

Cure Rates
- Over 90% cured with first- or second-line therapy.
  
  "Over 90% of patients are cured... and go on to recover from treatment and to live fairly normal lives." — Dr. Moskowitz [14:22]
Late Effects & Monitoring
- Secondary malignancies (thyroid, GI, leukemia, breast in women treated with chest irradiation)
- Cardiopulmonary toxicity (anthracycline-induced cardiomyopathy, pulmonary toxicity)
- Surveillance includes physical exams, targeted imaging, and bloodwork based on individualized risk.
- Early and intensified secondary cancer screening may be recommended.

Reducing Treatment Toxicity

De-escalation of Therapy
- Focus on minimizing late toxicity, especially from radiation, in young patients.
- Use of interim PET scans after two chemotherapy cycles:
  - PET-negative patients may receive shorter chemo, omit radiation.
  - Especially prioritized for younger patients due to decades-long risk.
- In Europe, PET-guided regimens (e.g., 'Bricad' protocol) allow further tailoring.
  
  "There are several studies that have shown that patients who have a negative PET scan... can often get away with a shortened course of chemotherapy and no radiation therapy." — Dr. Moskowitz [16:59]

Fertility Preservation

Key Counseling Point
- Pre-treatment counseling is critical, as even low-risk regimens can shorten the reproductive lifespan (especially for young women).
- Men are also encouraged to bank sperm as a precaution.
  
  "I often encourage fertility preservation before starting treatment...it's better to take care of the fertility preservation before anything starts." — Dr. Moskowitz [19:24]

Notable Quotes & Memorable Moments

On B-Symptoms:

"There's night sweats — drenching night sweats, where someone needs to change their clothes or their sheets ... Fevers are another one. And then weight loss, which is typically defined as losing 10% of your weight." [07:14]
On De-escalation:

"We are generally using this particularly for patients with early stage disease ... to decide whether or not we could potentially give patients fewer cycles of chemotherapy and also avoid radiation therapy." [16:59]
On Fertility:

"I see it as almost an insurance policy...It's better to take care of the fertility preservation before anything starts so that we don't have to worry about how the treatment's going to impact fertility further down the road." [19:24]

Key Timestamps

Epidemiology & Risk Factors: [01:29] – [03:21]
Role of EBV: [03:21] – [04:07]
Diagnosis & Subtypes: [04:07] – [05:04]
Clinical Presentation & Symptoms: [05:04] – [07:02]
B Symptoms & Staging: [07:02] – [09:14]
Treatment (Early & Advanced): [09:14] – [11:05]
Relapse/Refractory Cases: [11:05] – [12:39]
Allogeneic Transplant: [12:39] – [14:17]
Prognosis & Survivorship: [14:17] – [16:50]
De-escalation of Therapy: [16:50] – [19:19]
Fertility Preservation: [19:19] – [20:59]

Summary

This episode offers an authoritative, up-to-date guide for clinicians and patients alike, emphasizing the modern advances in treating classic Hodgkin lymphoma, the importance of survivorship care, and the ongoing shift towards minimizing long-term treatment-related harm. Particularly engaging is the focus on individualized care — from risk-adapted therapy to proactive fertility counseling — providing listeners with both the optimism of high cure rates and the practical considerations necessary for optimal long-term outcomes.

Loading summary

Transcript46 lines

[00:03]
A
Hi, I'm Derek Angus, a senior Editor at JAMA and host of Healthy Dialogue, a new podcast from the JAMA Network. Join me as we go beyond the latest discoveries with nuanced, in depth conversations with the world's leading experts to explore the most pressing issues in health and healthcare, from trends in autism diagnosis to private equity acquisition to AI and much, much more. Visit JAMA networkaudio.com or search Healthy Dialogue wherever you get your podcast to subscribe.
[00:46]
B
From the JAMA Network. This is JAMA clinical reviews, interviews and ideas about innovations in medicine, science and clinical practice.
[00:55]
C
Hello and welcome to our listeners around the world. I'm Dr. Kristin Walter, Deputy Editor at JAMA. I'm joined today by Dr. Allison Moskowitz, Associate Attending Lymphoma Service, Memorial Sloan Kettering Cancer center in New York, New York. Today we will be discussing a JAMA article that she co authored with Dr. Kishan Patel titled Classic Hodgkin Lymphoma A Review. This article was published online in Jama on August 3rd and there's a link to the article in the episode description. Dr. Moskowitz, thank you so much for joining us on this podcast.
[01:30]
B
Thank you so much. It's great to be here.
[01:32]
C
Before we start, I wanted to acknowledge that although Classic Hodgkin's lymphoma is the full name of this disease, I'll be using the term Hodgkin's lymphoma during this podcast to start off. Your article states that Hodgkin's lymphoma, which is a lymphoid malignancy derived from B cells, was diagnosed in about 82,000 people worldwide in 2022 and about 88,700 people in the US in 2025. What is the typical age of diagnosis of Hodgkin's lymphoma?
[02:01]
B
The majority of the patients that we see with Hodgkin lymphoma tend to be young. The median age is in the 20s, although there is a bimodal distribution where we see a group of patients who are in their 20s to 30s. But then we also see a group of patients who are over 60 as well, but they tend to be the less frequent patients that we see with this disease.
[02:24]
C
And what are some known risk factors for Hodgkin lymphoma?
[02:28]
B
I would say that the majority of patients who come to us with a new diagnosis of Hodgkin lymphoma, generally we don't know why they developed it and so that is more the typical scenario. There are certain risk factors that have been identified, such as having immune deficiency. There is a higher rate of Hodgkin lymphoma in patients who have a family history, but generally I would say for the majority of patients, we don't know why they develop it.
[02:56]
C
And is there a familial predisposition for Hodgkin's lymphoma?
[03:01]
B
Yes. So there is a familial predisposition for Hodgkin lymphoma. There are higher risks among siblings and particularly higher risks among twins. And so that has been reported. Sometimes we see multiple people within the same family developing it. These are rare situations, but we do see it.
[03:22]
C
And can you also discuss Epstein Barr virus and the link with Hodgkin's lymphoma?
[03:27]
B
The Epstein Barr virus or the virus that causes mono is positive in 90% of the population, but there is a link between the virus and Hodgkin lymphoma. I'd say that in Hodgkin lymphoma itself, about 40% of the cases of Hodgkin lymphoma are positive for the EBV virus and seem to be very closely linked to the development of the disease in those patients. Why certain patients end up developing EBV related Hodgkin lymphoma, we don't always know. It does tend to be more commonly seen in patients who have immune deficiency, and we also see it more commonly in older patients with Hodgkin lymphoma.
[04:07]
C
And your article discusses how the diagnosis is typically based on an excisional lymph node biopsy that reveals Reed Sternberg cells in a polymorphous inflammatory infiltrate and that the 2022 World Health Organization classification system includes four histologic subtypes, which are nodular sclerosis, mixed cellularity, lymphocyte rich and lymphocyte depleted. Which of these subtypes is most common in the US and is there geographic variability in subtype frequency?
[04:39]
B
In the US the most common subtype is nodular sclerosing subtype. We see that more commonly in the younger patients who develop Hochulmphoma and as well as patients with an int immune system. The other subtypes, such as mixellularity or lymphocyte deplete we tend to see in areas with reduced resources and also the mixellarity we tend to see in older patients.
[05:05]
C
And what is the typical presentation of patients with Hodgkin lymphoma?
[05:09]
B
I'd say the most common presentation is potentially a lump in the neck that someone palpates, often they may come to the attention of their primary doctor. And this enlarged lymphadenopathy may be considered to be potentially an infection. And they may first get a course of antibiotics, but then typically the lump will persist and that will lead to a biopsy.
[05:33]
C
And how often is it incidentally found on imaging?
[05:37]
B
It's not typical that Hodgkin lymphoma is found incidentally on imaging because it usually grows on the faster side. So usually it comes to someone's attention either through a lump in the neck or. Or through potentially symptoms from a mass in the chest, which could be cough or shortness of breath. Many patients will have B symptoms such as fevers or night sweats. Some patients will have pruritus that sometimes can be very debilitating or last for quite a long time before the diagnosis is made. So all of these things can be very nonspecific. But one of these symptoms tends to lead to the diagnosis.
[06:16]
C
And your article also mentions alcohol associated pain that's highly specific for the diagnosis. Can you describe this symptom and how frequently does this occur?
[06:27]
B
This is one of those classic symptoms that we think about with Hodgkin lymphoma, but it's really rare that we see it. So it's pretty unusual. But what it is is that basically someone will have pain in their area of lymphoma upon drinking alcohol. And sometimes someone will have the story of every time they drink alcohol, they have pain in their neck or in their back or in their chest. And so as a result, they stopped drinking alcohol. And sometimes that can be months before they even have the diagnosis of Hodgkin lymphoma. But it is one of those textbook symptoms that people get, but we see it quite rarely.
[07:02]
C
And you briefly mentioned the concept of B symptoms. Can you describe what these symptoms are and approximately how many of patients have B symptoms and what is their significance in terms of staging?
[07:15]
B
There are really three parts to the B symptoms. There's night sweats. And really what we're thinking about with night sweats, it's drenching night sweats, where someone needs to change their clothes or change their sheets in the middle of the night because of the sweats. Fevers are another one. And then weight loss, which is typically defined as losing 10% of your weight. And so having bee symptoms is considered to be one of the risk factors within patients who have early stage disease. So with early stage disease, we tend to categorize patients as either being in the favorable group or an unfavorable group. And one of those factors that has someone meet criteria for having unfavorable Hodgkin lymphoma is having B symptoms. For advanced stage disease, having B symptoms isn't considered to be one of the risk factors. And as far as how many people have B symptoms, it's about 30 to 40% of people with Hodgkin lymphoma.
[08:12]
C
And you've mentioned early stage disease, which includes stage one and stage two, and that it's risk stratified based on the presence of favorable or unfavorable features. In addition to the B symptoms. What are some other unfavorable features?
[08:26]
B
Another unfavorable feature is having a bulky mediastinal mass. Classically, that's defined as having a mass that measures 10 centimeters or more. Another one is having extension into extranodal sites of disease. So an extranodal site means it's outside of the lymph node system. And although generally we think of someone who has extranodal sites of disease as having stage four disease, they can have an extranodal site. Even with early stage disease, it just means that the disease is growing into an organ, such as a lymph node in the chest growing into the lung. So it's direct extension as opposed to a distant area. And then finally, it's also the number of lymph node sites. So having more than three separate lymph node sites is considered a risk factor as well.
[09:15]
C
And moving on to treatment, how is early stage Hodgkin's lymphoma treated?
[09:20]
B
The standard of care is to give chemotherapy and potentially with or without radiation therapy. And the amount of treatment that we give does depend upon whether someone is considered to have favorable or unfavorable disease. Now, I hate the terms favorable or unfavorable, because the cure rate for both favorable and unfavorable disease is very high. But the reason why we use these distinctions is that we can get away with less treatment for patients who are considered to have favorable disease. So fewer cycles of chemotherapy, a better chance of avoiding radiation. Whereas for patients who have what we consider to be unfavorable disease, we do tend to give increased number of cycles of treatment.
[10:03]
C
And how is advanced stage Hodgkin lymphoma treated?
[10:07]
B
The treatment for advanced stage disease has gotten quite simple recently. We always use chemotherapy, and now it's in combination with a drug called nivolumab, a drug that targets PD1. So the most common regimen that's given in the US is nivolumab, plus three different chemotherapy drugs called adriamycin, vinblastine and dacarbazine. So we call the regimen NIVoAVD. And the standard course of treatment is to give six months of treatment, which includes 12 treatments. And this is now the standard of care, based upon a study that was published about a year and a half ago, which was called the S 1826 Study, which was a study for patients who had stage three or stage four disease and they were randomized to either receive this nivo plus AVD regimen versus the older standard of care, which was brantuximab vedotin plus avd. So this nivo plus AVD regimen is now the standard of care.
[11:06]
C
Your article also discusses relapsed or refractory Hodgkin lymphoma. What percent of patients experience these conditions and how soon does this usually occur after diagnosis?
[11:18]
B
So the chance of having relapse or refractory disease has become lower and lower over time because the treatments in the frontline setting have gotten better. So for a patient who has early stage disease, the chance is about 10% or less. And then for patients who have advanced stage disease is also less than 10%, based upon the data from the most recent studies that have incorporated the novel agents such as nivolumab or Brentuximab. And as far as the timing of relapse, generally it's close to the timing of completion of treatment. So we tend to see it's most commonly within the first year and then potentially in the second year after completing treatment and becomes exceedingly uncommon beyond two years after completing treatment.
[12:06]
C
And what is the treatment for relapsed or refractory Hodgkin's lymphoma?
[12:10]
B
The standard of care for relapsed refractory Hodgkin lymphoma is to receive an additional regimen that is different from the frontline treatment. And there are several different options available. And then the goal of that treatment is to achieve a complete response on PET imaging. Once the patient achieves remission with their second line treatment, we then consolidate the treatment with an autologous stem cell transplant.
[12:39]
C
And when are patients treated with an allogeneic stem cell transplant?
[12:44]
B
So it's rare that we're using allogeneic stem cell transplant for Hodgkin lymphoma. And the reason is that the cure rate for Hodgkin lymphoma is quite high after frontline treatment. And then for the patients who are not cured with frontline Treatment, we do have a very good chance of curing them in the second line setting as well with an autologous stem cell transplant. And once it was determined that drugs targeting PD1, such as nivolumab and pembrolizumab, are highly effective in Hodgkin lymphoma, we learned that we can actually control the disease quite well for people who have relapse or refractory disease. And that led us to delay use of an allogeneic stem cell transplant because the allogeneic stem cell transplant has risks associated with it. There is a chance of graft versus host disease. There's a chance of even mortality as high as 10 to 15% with the treatment. So I'd say that we are very hesitant to use it in our patients. Although that all being said, we're now seeing that the efficacy has improved recently with as many as 50% or more patients achieving long term REM, and that's probably the result of them being exposed to PD1 blocking agents. And so getting back to your question of how often do we use it? So it's quite rare, I guess the situations where we might use it is for patients who have progressed or are no longer able to tolerate the best drugs that we have for Hodgkin lymphoma, which are the drugs that target PD1, as well as Brituximab, vedotin.
[14:18]
C
And moving on to prognosis, how often is cure achieved?
[14:22]
B
Over 90% of patients are cured either through their frontline treatment or through the second line treatment. And so the majority of the patients will go on to recover from treatment and to live fairly normal lives, thankfully.
[14:38]
C
And after treatment for Hodgkin lymphoma, survivors have an increased risk of secondary malignancies, cardiopulmonary dysfunction, and thyroid dysfunction. Can you discuss this? And which cancers are most common among these patients?
[14:51]
B
With regard to start with thyroid dysfunction, we do see thyroid dysfunction for patients who have been exposed to PD1 blocking agents. And then also there's a risk of thyroid dysfunction as well as thyroid cancer for patients who received radiation to their neck. And so this is something that we monitor for thyroid dysfunction. And then as far as monitoring for secondary malignancies in that setting, we tend to do through physical examination. For cardiovascular disease, there is a risk of cardiomyopathy related to anthracycline, as patients will receive up to 300 milligrams per meter squared of adriamycin with their initial treatment. And so this is monitored with an echocardiogram that's done within a year of completing treatment and then repeated later on if they develop any worrisome symptoms. As far as secondary malignancies, there is a higher risk of malignancies, potentially GI malignancies, and the risk of secondary leukemia related to chemotherapy. So with regard to the risk of leukemia, the monitoring is just through follow up and monitoring, routine blood work. And with regard to GI malignancies, there's not a specific follow up, but it's more having a high index of suspicion and referring a patient for evaluation if they're having any GI related symptoms. And then finally there's a risk of breast cancer for patients who received radiation to their chest. And the monitoring for that is to begin monitoring earlier than we would for the general population. And it's generally recommended that we start that monitoring about eight years after radiation or sooner if they're at the age where they would get routine monitoring. And then we tend to use more intense monitoring where we alternate with mammogram and ultrasound as well as breast MRI on a every six month basis.
[16:50]
C
And your article discusses how de escalation of therapy has become a focus of study to minimize treatment related morbidity. Can you discuss this?
[16:59]
B
Yeah. So we are generally using this particularly for patients with early stage disease. And we right now are using an interim PET response to decide whether or not we could potentially give patients fewer cycles of chemotherapy and also avoid radiation therapy because many of these later side effects of treatment are related to radiation therapy. And also many of them are related to the number of cycles of treatment that patients receive. So for early stage disease, there are several studies that have shown that patients who have a negative PET scan, meaning a PET scan that shows normalization or no evidence of active disease after two cycles of treatment, can often get away with a shortened course of chemotherapy and no radiation therapy. And we tend to use treatment paradigms like that more commonly in patients who are younger, where the late risks of radiation can be more significant because they have many, many more decades of life ahead of them. And so that's what we've been now using for patients with early stage disease. For older patients, the risks of radiation are really minimal. And so as a result, we often will use our older approaches where we use combined modality therapy, meaning chemotherapy followed by radiation therapy for advanced stage disease. Right now we're generally not using response adapted therapy, at least in the US where we're using the nivolumab plus AVD regimen. But that may change as there's studies that are looking to see if we can use cell free DNA or circulating tumor DNA to modify therapy and potentially allow patients receive less treatment. The regimen that is used more commonly in Europe and particularly in Germany, which is the Bricad regimen which was developed by the German Hodgkin Study Group. This is a regimen that is pet guided. So patients initially receive two cycles of treatment and if their pet is normal after the two cycles they receive just a total of four cycles. If their pet remains positive after two cycles then they receive a total of six cycles. So there are risk adapted approaches that are used with some of the regimens for advanced stage disease before closing Is
[19:20]
C
there anything we didn't discuss in this podcast that you'd like to mention?
[19:24]
B
I would like to mention fertility preservation because this is something that is very, very important. I would say for every young individual who has newly diagnosed Hodgkin lymphoma, many of our treatments that we use for newly diagnosed disease such as abvd, actually has a very low risk of causing infertility. But that being said, even young patients receiving ABVD or Nivolumab plus abd, even though they may regain their fertility after completing the treatment, they do have a shortened lifespan of fertility with any of these treatments and so they may go into menopause earlier than they would have had they not received the treatment. That's one reason why I often encourage fertility preservation before starting treatment. And the same goes for men. I think it's very important for them to undergo fertility preservation as well. And the second reason is that I see it as almost an insurance policy because although we mentioned that the majority of patients will be cured with their frontline treatment, there's still patients who are not cured, and some of those patients need to go right into additional therapy. And that additional therapy, as we mentioned, may include an autologous stem cell transplant, which has a much higher chance of causing infertility. And because of that, it's better to take care of the fertility preservation before anything starts so that we don't have to worry about how the treatment's going to impact fertility further down the road.
[20:59]
C
Thank you so much for sharing your thoughts with us about this interesting and important topic.
[21:04]
B
Thank you so much. It was great to talk with you.
[21:07]
C
I'm Dr. Kristen Walter and I've been speaking with Dr. Allison Moskowitz from Memorial Sloan Kettering Cancer center in New York. You can find a link to this JAMA review article that we discussed in this episode's description. This episode was produced by Daniel Musisi at the JAMA Network to follow this and other JAMA Network podcasts, please visit us online@jamanetworkaudio.com or or search for JAMA Network wherever you get your podcasts. Thanks for listening.