Treatment of Hematologic Malignancies

May 24, 2021

Information

May 23, 2021

Yale Cancer Center

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00:00Support for Yale Cancer Answers
00:02comes from AstraZeneca, dedicated
00:05to advancing options and providing
00:07hope for people living with cancer.
00:10More information at astrazeneca-us.com.
00:14Welcome to Yale Cancer Answers with
00:16your host doctor Anees Chagpar.
00:19Yale Cancer Answers features the
00:21latest information on cancer care by
00:23welcoming oncologists and specialists
00:25who are on the forefront of the
00:27battle to fight cancer. This week,
00:29it's a conversation about Hematologic
00:31malignancies with Doctor Francesca Montanari.
00:33Doctor Montanari is an assistant
00:35professor of clinical medicine and
00:37hematology at the Yale School of Medicine,
00:39where Doctor Chagpar is a
00:42professor of surgical oncology.
00:43Francesca, can we
00:44start off by you telling
00:46us a little bit about Hematologic
00:48malignancies, what they are,
00:51how common they are, and how people who have
00:54a hematological malignancy can present?
00:58Hematological malignancies
00:59include all types of blood cancers.
01:03So these are cancers that can affect the
01:07bone marrow where the blood cells are made,
01:11blood cells, lymph nodes and other
01:14parts of the lymphatic system and
01:17typical hematological malignancies
01:18or blood cancers are leukemias,
01:21lymphomas, Myelomas,
01:22and others that are rare, such as
01:26myelodysplastic and Myeloproliferative disorders,
01:29and these diseases represent less
01:31than 10% of all the cancers,
01:34and there are approximately 1.8
01:37million new cases of cancer per year
01:40in the United States and approximately
01:43180,000 cases of blood cancers.
01:46So every 3 minutes,
01:47one person in the US is diagnosed
01:51with one of these diseases.
01:53Approximately half of the blood
01:57cancers are lymphomas which account
01:59for 86,000 cases per year.
02:02They are further divided in Hodgkin
02:04and non Hodgkin,
02:06which are the most common
02:08and then Hodgkin is
02:10classified into over 60 distinct subtypes.
02:14So as you can imagine,
02:16numbers tend to become very very small
02:20for the most rare of these subtypes.
02:27Leukemia is approximately 60,000 cases
02:30per year and less than 10% are myelomas,
02:33so symptoms and manifestation
02:35of these diseases can vary.
02:38There is a very wide range of
02:41symptoms that can be associated
02:43with any of these blood cancers,
02:46which depends on the specific
02:49disease and the localization.
02:51For instance,
02:51lymphoma can present with the so-called
02:54constitutional symptoms,
02:57which are very
02:58specific, fever, chills,
03:01night sweats,
03:03unintentional weight loss.
03:06But there are a lot of other
03:08symptoms which depend on the specific
03:11localization of the disease.
03:13For instance,
03:13there are lymphomas that like to
03:16affect the gastrointestinal tract,
03:18and they cause gastrointestinal disturbances.
03:20Other lymphoma can involve the
03:22eye or the structures around the
03:24eye causing trouble with vision,
03:27or they can affect the skin.
03:29And as you can imagine,
03:31depending upon the organ that is involved,
03:34you can have very different symptoms.
03:37Leukemia tends to present with
03:39symptoms related to the bone marrow
03:42involvement and the cytopenias such
03:44as fatigue from the anemia,
03:47bleeding from low platelets,
03:48infection from low blood white cell
03:51count and multiple myeloma also
03:53can present with fatigue from anemia,
03:56infection and bone pain.
03:58But bone pain is a more distinct
04:01sign of a multiple myeloma as
04:04it involves the bone structure and
04:07can cause pathological fractures.
04:09Lethargy and other gastrointestinal
04:12symptoms related to the hypercalcemia
04:14also can be present at presentation.
04:17That seems like just an amazing
04:20potpourri of symptoms and
04:23sites that these blood cancers
04:26can harbor in so how
04:29do patients find out that they have
04:33one of these hematologic malignancies?
04:35It seems like they can be
04:39anywhere from your bone marrow to your eyes,
04:43to your gastrointestinal tract,
04:45and the symptoms can be completely
04:48nonspecific, like a little bit of
04:51fatigue to having visual loss
04:53or gastrointestinal problems.
04:56So how is the diagnosis actually made?
05:06It depends on the various scenarios.
05:11Some of these blood cancers
05:14tend to be
05:16very slow growing and might be picked up
05:20incidentally,
05:20just performing some routine blood
05:23work by the primary care physician
05:26on occasion of the well being visit.
05:29So finding a new presence of
05:32increased protein in the blood
05:35might raise the suspicion of myeloma
05:37and determine additional
05:41testing that eventually lead
05:44to the diagnosis and in other
05:47cases the symptoms can be more
05:50prominent and therefore as part
05:53of the initial investigation by
05:56the primary care physician,
05:59certain signs and symptoms
06:01might be detected that raise a
06:04flag for this condition,
06:06and further evaluation
06:08include imaging studies and
06:09more in depth blood work
06:13and eventually valuation by a blood
06:16cancer specialist and so once that
06:19happens, once they come to
06:22you as a blood cancer specialist,
06:26what's the next thing that happens?
06:30So typically we
06:31do really need to run a
06:34little bit more of a work up,
06:37and that includes imaging studies,
06:39which can be anything from MRI or CT scan,
06:43even a newer form of CAT scan
06:47that is called PET Scan where we
06:50use glucose to track down in the
06:54body where there is an increase in
06:57the metabolic activity that may
07:00reveal the presence of a cancer.
07:03And ultimately the diagnosis
07:06is made through a pathology,
07:08so we would need a tissue sample either
07:13from a lymph node or from the bone marrow.
07:19Or sometimes a blood sample is
07:23sufficient where we do run specific
07:27tests to detect these diseases and
07:30once we have a pathological confirmation
07:34then other tests might be warranted
07:38depending on the nature of the disease
07:41and typically this test helps us with
07:46prognostication and with staging.
07:49Let's talk about that.
07:52How do we determine prognosis?
07:54And in general, what is the
07:56prognosis of these hematological
07:57malignancies, understanding,
07:59however, that this is a
08:01varied group of diseases that
08:04are lumped into this basket term.
08:07Right, so there is a lot of variability
08:12in the behavior of these diseases,
08:16and as we have improved our knowledge
08:20in the biology and mechanism
08:23that drives these diseases,
08:27we have a very complex way to
08:32assess prognosis and prognosis
08:35typically depends on very general
08:41information
08:42such as the burden of
08:45disease at presentation, and
08:47the performance status of the
08:50patient plays a big role and
08:54the presence of comorbidities or
08:56end organ damage from the disease,
09:00and then there are other markers that we
09:06gather from the pathology evaluation
09:09and from the genetic makeup through
09:13molecular studies and based on each
09:16disease as a specific list of
09:20features that we pay attention to
09:23when we determine the risk
09:25stratification and ultimately
09:27based on all this information,
09:30we determine what is the
09:33best treatment approach.
09:36What is the treatment
09:39approach for these cancers
09:41in general?
09:43The type of approach is very variable.
09:46So first of all, the most important
09:51point that I'd like to make is that,
09:56as I mentioned, the behavior of
09:58blood cancer is very variable.
10:01There are blood cancers that are
10:04very indolent and slow growing.
10:07And we don't necessarily start
10:10treatment upon diagnosis.
10:12These diseases are considered
10:14generally not curable, but very,
10:17very manageable and treatable
10:19with certain drugs.
10:22And the most important thing upon
10:26diagnosis is determining if a patient
10:31requires treatment or can be watched.
10:35We call that
10:37watchful monitoring,
10:39and once there is an indication
10:42when therapy is warranted,
10:44then the decision of which kind of therapy
10:49depends on the specific type of disease,
10:54the staging of the disease,
10:56and the predicted behavior,
10:58which is usually based on the genetic
11:00makeup of the specific blood cancer.
11:03Another important factor that
11:05helps the decision about the best
11:08strategy is based on patients
11:10characteristics such as the age,
11:12the performance status,
11:14the presence of medical conditions
11:16which might have an impact
11:18on the tolerability of the
11:20treatment and if transplant,
11:22if bone marrow transplant can be
11:25used for that
11:27specific patient,
11:28as part of the treatment strategy.
11:30Another factor that is very important is
11:33a patients preference now that
11:35we have multiple therapy options
11:38which offer similar results
11:40in the long term but differ in
11:43terms of administration
11:45modality and side effects profile.
11:47Patient preference might play a
11:49big role in the final decision.
11:55During the past year there is another
11:58factor that has played
12:02a big role in our decision making,
12:05which has been the COVID pandemic.
12:08So having an aggressive blood cancer
12:11that requires treatment and has not
12:14had any variation.
12:17But because of the presence of the COVID pandemic,
12:19for those diseases that are
12:21more indolent and not immediately
12:24life threatening,
12:25we have been shifted away from
12:28using certain drugs or certain
12:31strategies to maintain the disease in
12:35remission for longer period of time.
12:38Unless there was an overall survival
12:41benefit in order to minimize the
12:43risks of increasing the severity and
12:46mortality from the infection.
12:51There's a few points there that you
12:54mentioned that I want to pick up
12:57on and the first is that some of
13:00these diseases are fairly indolent
13:02and may not require treatment.
13:04This kind of expectant
13:06watchful waiting approach.
13:07How do you determine whether
13:09that's the case for patients,
13:11particularly when you mentioned that
13:14many of these cancers are not quote
13:17curable but they are manageable?
13:19And do patients get some anxiety over
13:23the idea that they may have a cancer
13:27that were simply watching?
13:30It's very important to have that
13:33clear communication with the patient
13:35that initiating treatment earlier
13:37for this kind of cancer does not
13:41necessarily translate in a prolongation
13:43of their life expectancy and the
13:46goal of the treatment in their case
13:50is to minimize the toxicity related
13:53to the use of certain agents and
13:56maximizing the effect in terms of
14:00allowing them to live their normal life
14:04without having any side effects from
14:07either the treatment or the disease.
14:11So important to
14:13have good communication.
14:14We're going to learn a
14:16lot more about hematological
14:18malignancies right after we take a
14:20short break for a medical minute.
14:23Please stay tuned to learn more with
14:25my guest Doctor
14:27Francesca Montanari.
14:28Support for Yale Cancer Answers comes from
14:31AstraZeneca, working to eliminate
14:32cancer as a cause of death.
14:35Learn more at astrazeneca-us.com.
14:38This is a medical minute
14:40about head and neck cancers,
14:42although the percentage of oral
14:44and head and neck cancer patients
14:46in the United States is only about
14:485% of all diagnosed cancers,
14:50there are challenging side effects
14:52associated with these types
14:54of cancer and their treatment.
14:55Clinical trials are currently
14:57underway to test innovative new
14:59treatments for head and neck cancers,
15:01and in many cases less radical
15:03surgeries are able to preserve nerves,
15:05arteries and muscles in the neck,
15:08enabling patients to move, speak,
15:10breathe and eat normally after surgery.
15:13More information is available
15:15at yalecancercenter.org.
15:16You're listening to Connecticut Public Radio.
15:20Welcome back to Yale Cancer Answers.
15:22This is doctor Anees Chagpar
15:24and I'm joined tonight by my
15:27guest doctor Francesca Montanari.
15:28We're talking about the care of patients
15:31with hematologic malignacies and
15:33Francesca right before the break we
15:35were talking about the fact that these
15:38hematologic malignancies are so varied,
15:40varied in terms of where they present,
15:43some being in the bone marrow,
15:46some being in the lymph nodes,
15:48some being organs like
15:51eyes and GI track and bone and other
15:54places, they are varied in terms of
15:56their clinical presentation and the
15:59symptoms that they cause
16:01in terms of their clinical course.
16:04Some being very indolent and slow
16:06growing such that they wouldn't even
16:09warrant necessarily treatment and
16:10others being far more aggressive.
16:13Can you tell us a little bit
16:15more about the cancers,
16:17specifically what you treat?
16:19Is there a certain type of
16:21these hematologic malignancies
16:23that you specialize in?
16:25Yes, so in terms of blood cancer
16:30my research interest has
16:33always been on the lymphoma side.
16:36So lymphomas by themselves
16:39constitute the
16:42biggest part of the blood cancer.
16:45They are approximately half
16:47of all the blood cancers,
16:50but they are very diverse themselves
16:53and we do typically
16:57divide them into big categories,
17:00Hodgkin and non Hodgkin,
17:03and then furthermore into
17:05aggressive and indolent in the
17:08non Hodgkin lymphoma type and
17:11so the focus of my research
17:14has been in trying to better
17:18understand the biology of the more
17:22rare of these lymphoma types.
17:25And based on the insights in the
17:29biology to develop new treatment
17:32strategies that are targeted
17:35for these less known subtypes.
17:38In particular,
17:39the focus of my research over
17:42the past decade or so has been on
17:47posttransplant lymphoproliferative disorders,
17:49which are a rare lymphomas that arise
17:53as potentially life threatening complication
17:57of solid organ transplant.
17:59These are lymphomas that arise in the
18:02setting of reactivation of infection
18:05due to the immunosuppressive treatment
18:08or due to the chronic dysregulation
18:11of the immune system in the setting
18:15of chronic immunosuppression,
18:17and historically,
18:18the prognosis of these lymphomas have
18:21been very poor because of inability
18:24to deliver full dose treatment.
18:27And due to the frailty and
18:30risk of infectious complication
18:32that this patients experience with a
18:36regular conventional chemotherapy,
18:39the risk of dying of infection
18:42during treatment in this population
18:44has been estimated around 30%,
18:47which is extraordinarily high and
18:50in order to try to minimize the
18:53complication from the treatment,
18:56I developed the
18:59risk stratified treatment adapted
19:02strategies which are based essentially on
19:08induction phase
19:08where we do
19:11not use cytotoxic chemotherapy but
19:14more a targeted antibody approach.
19:17And then we do reserve escalation
19:20to chemotherapy only to patients
19:23that do not achieve a full response
19:26on the least invasive treatment.
19:30And with these strategies we have
19:33been able to
19:35limit the use of cytotoxic agent
19:38to less than half of the patient
19:41population that we do treat.
19:43Another area
19:46where I've been conducting
19:48research is in T cell lymphoma.
19:51Those are also very rare lymphomas.
19:54They are much rarer than the B cell
19:57lymphoma which are the most common
20:00non Hodgkin lymphoma out there
20:02and unfortunately historically we
20:05have been using
20:07a treatment
20:08that has been extrapolated from
20:11the B cell counterparts,
20:13so not really specific to these
20:16subtypes of lymphomas and the
20:19results are not as optimal as in
20:22the B cell counterpart's.
20:25Over the past few years,
20:284 new drugs have been approved in
20:30the space for this, specifically
20:32for T cell lymphoma and one of
20:35the challenges that we have now
20:38are trying to identify
20:40what is the best sequencing of this
20:42agent and what is the best way to
20:45combine them to improve the outcome
20:48of patients with additional malignancies.
20:52It sounds like in both of those
20:54scenarios the overarching theme
20:57is really personalizing treatment
20:59to the patients individual disease,
21:01so I wanted to just take a step back
21:05and talk a little bit more about
21:08the intricacies of each of these.
21:12So with regards to the post transplant
21:14lymphoma, help us to understand
21:17again how these lymphomas occur,
21:19'cause certainly there are listeners
21:22who may have gone through a solid organ
21:25transplant or may know someone who has and
21:29these patients are on immunosuppressives.
21:33So does that immunosuppressive
21:35therapy automatically increase
21:36their risk of lymphoma?
21:38And is there anything that they can do to
21:43reduce their risk of developing lymphoma
21:46in that setting?
21:48That's a really good question,
21:51so we do after the transplant patient
21:55received different immunosuppressive
21:56treatment which are related to the different
22:00kind of transplant that they have received.
22:03For transplant,
22:05such as intestinal transplant,
22:07multi visceral transplant,
22:09immunosuppressive treatment is much tougher
22:12and much deeper than a patient that
22:15for instance receives renal transplant where
22:19immunosuppresant treatment required
22:21for the recipient to accept the graft is much less.
22:33And the reason we do see as a
22:36consequence of the immune suppression
22:38reactivation of common infection,
22:40and most important,
22:42is the Epstein Barr virus,
22:44which is the virus that causes mononucleosis.
22:47Most of the adult population has been
22:50exposed by adulthood to the virus,
22:53and the virus is dormant in
22:56a silent state in our body,
22:58and is kept at bay by our immune system.
23:02So conditions such as immunosupression where
23:05our immune system defenses are lowered
23:08allow the virus to thrive again
23:11and replicate and
23:14this particular kind of virus,
23:17in the absence of an immune system
23:21that fights it and keeps it at bay,
23:25is able to transform the blood
23:29cells into lymphoma cells so
23:33typically in the first year
23:35after the transplant,
23:36most of the lymphoma that we do
23:39see are related to Epstein Barr
23:43reactivation in the
23:45setting of the immune suppression,
23:47the lymphoma that arise after one
23:50year still can be
23:53linked to the Epstein Barr virus,
23:56but approximately half of them happen
23:59without a reactivation of Epstein virus,
24:01and they do not hardwire the genetic
24:05material of the virus and are
24:07thought to arise in the setting
24:10of a chronic immune dysregulation
24:13due to the longstanding immunosuppression.
24:17Is there anything that
24:19people can do to limit that
24:21reactivation of Epstein Barr virus?
24:24You mentioned that most adults have
24:27already experienced Epstein Barr virus,
24:29and so should have some degree
24:31of natural immunity to the virus,
24:34although they're on immunosuppresants.
24:36So has anybody looked at ways that
24:39people who are on immunosuppresants
24:41can prevent that reactivation?
24:44That is a really good question, and
24:47indeed,
24:49a part of these
24:52strategies in the period after transplant
24:56include close monitoring of the
24:59EBV presence in the blood.
25:02So after a solid organ transplant,
25:05depending on the kind of solid
25:10organ transplant there are
25:12algorithms
25:14and there is a monitoring of the
25:19EBV which is done
25:23in certain cases twice a month.
25:26Other cases once a month,
25:29depending on the nature of the
25:32immunosuppression and preemptive
25:34strategies to intervene.
25:38Treating the EBV before the lymphoma
25:41appears has been attempted,
25:43but the results are not optimal
25:47because there is a lot of variation in
25:50the levels of EBV that is noted
25:54in patients post transplant and not
25:57everybody that experience a reactivation
26:00of the virus end up developing a
26:04lymphoma and therefore there is not
26:07good guidance out there regarding
26:10who to treat preemptively
26:13and who to observe.
26:15When I was at Columbia University prior
26:20to joining the group here at Yale
26:24I was leading the effort to come up with
26:28with guidelines to help clinician in the
26:33solid organ transplant team to troubleshoot
26:38these problems,
26:39meaning want to check the EBV
26:43at what intervals and what
26:47is the threshold of the
26:51virus to consider potentially
26:54leading to a lymphoma and when
26:58to utilize treatment to reduce
27:01that virus level and it is still a
27:04discussion and a work in progress.
27:09And do we know what factors
27:11kind of trigger that EBV
27:14to turn into a lymphoma?
27:17Because potentially that's another
27:19place to intervene in thinking about
27:21is there a way to
27:24potentially mitigate that transformation.
27:28That is an excellent
27:30question, and unfortunately the reason
27:33why EBV can turner in vitro
27:37into malignant cells is because
27:39one side triggers
27:43the proliferation of these cells and
27:46the other side blocks an important
27:49mechanism that is called apoptosis,
27:52by which the cells die but alone is
27:55not able to induce lymphoma in vivo.
27:59And the thought is that there are,
28:03like in all the other kinds of cancer,
28:08a multi step process where the
28:12cells progressively gain additional
28:14mutation and overtime
28:16the addition of this mutation together
28:19sort of cause the transformation into cancer,
28:27but we are not able in 2021 to predict
28:31which mutation and when these
28:34mutations are acquired.
28:36Doctor Francesca Montanari is assistant
28:38professor of clinical medicine and
28:41hematology at the Yale School of Medicine.
28:43If you have questions,
28:44the address is canceranswers@yale.edu
28:46and past editions of the program
28:48are available in audio and written
28:50form at yalecancercenter.org.
28:52We hope you'll join us next week to
28:54learn more about the fight against
28:57cancer here on Connecticut Public Radio.