announcer major fundingfor "second opinion" is provided by the bluecrossand blueshield association, an association of independent, locally operated,and community-based blue cross and blue shield companies.for more than 80 years, blue cross and blue shield companieshave offered health care coverage in every zip codeacross the country and supported programsthat improve the health and wellnessof individual members
and their communities.the bluecross and blueshield association's mission isto make affordable health care available to all americans.news about our innovations is online at bcbs.com and on twitter@bcbsassociation. "second opinion" is producedin association with the university of rochester medical center,rochester, new york. salgo: welcome to "second opinion,"where you get to see, firsthand, how some of thecountry's leading health care
professionals tackle healthissues that are important to you.i'm your host, dr. peter salgo, and today i'm happy to welcomedr. michael kalos from the university of pennsylvania.our "second opinion" primary care physician, dr. lou papa.dr. george sledge from indiana university.dr. deepak sahasrabudhe from the university of rochestermedical center. and judy orem, who'shere to share her story with us, a story that our panelists,along with you at home, are
going to be hearingfor the first time. are you ready to getright to work? panel: ready. for our purposes,december 7, 1995, you received some news thatchanged your life on that date. what happened? orem: my doctor called me after i'dhad a physical -- i felt fine,
but they did a blood test --she called me on the phone and said, "judy, i have anappointment for you tomorrow with a specialist."she said i had c.m.l., which was a leukemia.chronic myelogenous leukemia. um...that just sends chillsthrough your whole body when they say this. did you have any symptoms? no, no symptoms. nothing wrong?
nothing wrong. what on earth prompted herto look? my grandmother was diagnosedwith cml and died in '79 with cml. okay. my mother had cll --lymphoma cll -- in '91. and i didn't know it wasn'thereditary, you know, i thought, "all these othercancers are hereditary. i should be looking for this sothat i can catch it right away."
okay, so that's whyshe did it. yes. you told her to. and so you were a proactivepatient, and she called you and she said, "look, you may havethis." and what were your thoughts whenyou got the call? it was just sort ofdevastating. i called my husband.i called my kids. my husband said, "this isn'tsupposed to happen this way.
i'm supposed to be the one whogets something first, you know, and goes.you-you can't --" my son says, "they'll come upwith something, mom." you know. so this is 1995 when youbegan your war against cancer. but we can roll the clock back alittle bit to the nixon administration -- kalos: that's right.
when there was anannouncement of a war against cancer, as if doctors hadn'tbeen fighting this war for some time prior to that.i think it's time to take a look back and say, now that we'vebeen at war for about 40 years, how are we doing? sledge: well, there is no such thingas cancer, i think is the first place to start.the major thing we've learned in the last 40 years since nixon'swar on cancer is that there is
no cancer -- there are cancers.it's an entire family of diseases.i tell my fellows in clinic, you know, "view this asa boarding house. you know, where you've got agang of criminals hangs out. some of them are petty thieves.some of them are murderers. you've got to apprehend themdifferently. you've got to punish themdifferently. that's what we've learned in thelast 40 years. so the conceit was, i think,in this war on cancer, that
cancer was a disease, onedisease, and if we just got the medicine against that onedisease, we'd get rid of cancer. the other conceit was,perhaps we would come up with one cure.the magic -- one effect-- one treatmentthat will eradicate or eliminate all cancer, and thatwas clearly misguided. papa: i think we were lookingfor dramatics, too. we were treating it almost likeit was an infectious disease,
and that we'd find the thing andthen the next day the sun would rise and everything would bebetter, and it's -- i don't think it's been a long war,but there's been a lot of battles that have been won.i mean, there's been enormous advancementsover the last 40 years. but i think theconceit of this war on cancer was the magic bullet, to borrowanother phrase from medicine's past.if cancer is one disease, there will be one medicine, onevaccine, one bullet that you
just kill it, and we can go onand die of something else. how many kinds of cancers arethere? we're getting to thepoint where cancer is an individual disease. what does that mean? so your cancer is defined bycharacteristics that are, to some degree, unique to yourparticular cancer, and how it's treated will be based upon thatuniqueness. so individual diagnosis --
individualized diagnosis --and individualized treatments. but --as a condition, it's a fair word to put on it, "cancer." salgo : okay, that's where i wasgoing with this. if we're going to use the word"cancer," and we're also going to use your analogy of aboarding house full of bad actors, then there's lots ofkinds of cancer, right? there's lung, there's liver,there's pancreas, you name it.
you name a cell, there's acancer of that cell. what is it about cancer that makes it a common problemfor all of these diseases? and what makes it so fierce?why is it so dangerous? and that means, why is everybodyso terrified of it? even within an individual'scancer, there is complexity and heterogeneity.so the boarding house resides even within each one of ourcancers, if we were so unfortunate as to have one.that's part of what makes it fierce, is that you can targetand eliminate 99.9% of the bad
guys, and what's left has morespace and opportunity to regrow. can we back up again?since we just said cancer is a different disease in everyperson, a different disease for lots of different cells, and yetyou still want to use this umbrella term, "cancer."somebody help me out here. define "cancer."what does it mean? sahasrabudhe: well, it isa disorder wherein the growth is unregulated.cells continue to grow when they
shouldn't.they move out of their location and go to other sites.your lung always stays in your lung, but lung cancer will leavethe lung and go someplace else. so it metastasizes.and sometimes it can lay dormant. okay, so, if iunderstand, there are two characteristics of cancer that iheard while you were speaking. one is that cells grow wrongly.they don't stop. most cells -- most clumps ofcells grow for a while, then
some of the cells die, and newcells take their place. in cancer, they don't die.they just keep growing and growing and growing and getbigger. and they spread.that metastasis from "meta-," "-stasis."it doesn't stay in one place. correct. so liver cancer starts in yourliver with liver cells growing out of control.and it may go somewhere else. your lung, your brain,somewhere.
is that a fair diagnosisdefinition? it's fair. very reasonable, yes. there are smart cancers anddumb cancers. what do you mean by a dumbcancer or a smart cancer? so, stupid cancers or dumbcancers are cancers that have relatively few mutations.they may have just a single driver mutation -- can we stop for just asecond -- a mutation?
so, a mutation is a change inthe basic genetic makeup of a normal cell that turns it into acancer cell. and the gene is what tellsthe cell what to do -- when to grow, when to stop, when tolive, when to die. it's all there on the genes.the gene is the instruction manual for the cell. so a stupid cancer isone mutation, and a smart cancer is lots of mutations? yeah, one of the things we'velearned just literally in the
last two or three years is that,if you compare the entire range of human cancers, looking attheir genetics, there's a thousandfold difference betweenthe lowest and the highest in terms of the number of mutationsthat a cancer cell has. and some of these cancers arebreathtakingly brilliant -- they're very good at throwingoff every single treatment we throw at the cancer cell. so, "brilliant" isbad in cancer. "stupid" is good in cancer.now, judy, what kind of cancer
did you have? i had a stupid cancer.[ laughter ] hurrah! yours was cml.cml. chronic myelogenous leukemia.that's a good cancer from a patient's perspective.now, wasn't necessarily so good when you had it.no, no, it wasn't. so, what treatment optionsdid you have at the moment that you got the diagnosis?
at the moment was interferon.okay. i gave myselfinjections every day. and i did little marks down myleg, and then this one, and so -- and did those.i only got -- i still was left with 60% philadelphia chromosomeafter a couple of years. and the philadelphiachromosome is that marker in the chromosome in the blood cellsthat says you've got leukemia. correct.and where there is philadelphia chromosome, thereare cancer cells.
and if you had 60% philadelphiachromosome... yeah. all right.here you are. i want to place you in timeright now. you've been using interferon.the best you got was 60%. only 60% philadelphiachromosome. yeah, i still had 60%philadelphia. you got rid of 40%.got rid of 40%, but 60% ain't great.
no. and what were your doctorstelling you at that time? they put me on ara-c forsix months and said, "this probably should help," and atthe end of six months, they did another bone marrow biopsy andsaid, "you're at 100% philadelphia chromosome." that's worse. that's worse.so, if the ara-c did any good, it just delayed thingsa little bit.
so now you're at the endof the road. you've got a bone marrow filledwith cancer. the interferon you're usingisn't working. the other drug isn't working.what did they tell you, and what were you thinking? they told me i had sixmonths, maybe, before it would go, as they said, sort of wild. accelerated phase andblast crisis. blast crisis,accelerated phase, two phrases
you don't want to hear. correct.and they said they might be able to keep me alive for two yearswith massive chemo treatments. and what did you thinkof that? that wasn't really very good.you know, it wasn't what we were looking at, at the time. i want to pause andsum up what we've been talking about.cancer, as we discussed, is not a single disease.it may have one name, but it has
many different illnesses.there is breast cancer, colon cancer, prostate cancer, youname it. understanding the differencesand similarities in how these various cancers behave isessential to better treatment, and that's something we'velearned fairly recently during this war on cancer.let's get back to you, judy. it's three years after yourdiagnosis. you had leukemia.you learned your treatment was no longer working.did you just give up and work on
your bucket list? [ chuckles ] not quite.at the same time, i actually had -- was aware that theleukemia and lymphoma society had given dr. druker atoregon health and science university a translationalgrant -- back in '96 they announced it -- and i have afriend who called him and said, "i have a friend who should be,you know, you could maybe consider?"he called me and put me on a list.so i was on, during all this
time, there was this hope that,that he would finally get the drug ready to be donein a human trial. so let me justtranslate that. translational trials, all thismumbo jumbo, there was a doc with an experimental drug.you heard about it, and you might have fit the profile ofsomeone on whom that drug could be tried. yes, which i didn't know atthe time, i didn't until -- until i actually had failed andit was documented that i had
failed interferon and ara-c. you didn't fail interferon.interferon failed you. right, when it -- right,that's a good point. this treatment thatyou had heard about, you came to learn about it from one of yourfriends. did you research that?did you find out more about it? there wasn't a lot ofresearch, but dr. druker did send me letters every six monthssaying what was going on. he hoped to be ready for trials,trials got postponed for almost
a year, but it was at the sametime that that happened that the interferon failed me, so i wasthen really, truly a candidate to be on -- there was nothingelse to go for me. but you -- you know, that's arace, right? there's a delayin this new trial. by the way, the name of the drugwas...? orem; well, it was sti571, which isnow known as gleevec. gleevec.so they're racing to get this
drug ready for trials.you're racing to stay alive. and interferon isn't gettingit done for you anymore, but in a strange twist of fate, it'sonly those in whom the interferon has failed that wouldhave been candidates for the drug.so there you are at a precise time and space. yes, absolutely perfect.and you got enrolled in the trial? what number patient were you?
i was number 9. [ laughs ] number 9.let's go back to this war on cancer, because i think it'simportant to realize that, just as cancer is not one disease,the war is not just one war. it's individual little wars.there's the war against cml, right, there's the war againstall kinds of cancers. how are we doing on all frontsin this war? is it a war we're winning? it depends on whatyou're looking at.
i mean, when i speak to mypatients, there's more patients now surviving from cancer andgetting cured from cancer than ever before.but a lot of the bad players are really smart.lung cancer and stomach cancer and pancreatic cancer are stillbig players, and they're -- the progress on them has been slow. so why don't you, george,walk me through just a little bit about the history of cancertherapy? you may not have called it awar -- we may not have
called it a war, but we've beenfighting cancer since the 19th century. yeah, so we've been through abunch of different eras, in terms ofthe treatment of cancer. the first treatments were localtreatments, surgical treatments, followed by radiation therapytreatments that came along, well, certainly by 1950 or so.and then, starting in the 1950s, extending forward, we got intothe chemotherapy era, where we used nonspecific drugsthat basically work by killing
dividing cancer cells.cancer cells, because they divide, are particularlysensitive to drugs that kill dividing cells.then, then subsequently, starting perhaps more or lessat the same time, but starting very slowly and only recentlybuilding up, and you're, again, the poster child for that,are the targeted therapies -- the therapies that arespecifically interfering with a particular part of the cancercell's biology. hormonal therapies for breastcancer, her2 targeted
therapies for breast cancer.epidermal growth factor receptor targeted therapies forlung cancer. braf mutation targetedtherapy, just in the last two years, for melanoma.bcr-l targeted therapy for cml.this last decade has been the decade of targetedtherapies. i think we're actually movinginto a new era now, and this is the genomic era, the era wherewe're actually going to be able to identify the mutations inevery single patient's cancer.
and that's -- that, hopefully,is going to bring us a whole lot closer to a cure. it's exciting. that's very exciting forpatients, because one of the things that we kind of touchedupon but didn't say is that, in the war on cancer, there's alot of friendly fire. the therapies that we have doesa lot of damage to good tissue, you know, and that's one of thethings patients -- and my wife's going through it right now withbreast cancer -- that makes it
most difficult, so having theexcitement where you can be targeted and there's not so muchcollateral damage is very exciting for patients. the point i'd like to add tothis is, the war on cancer has been dependent on someincredible basic research that has helped us understandmechanistically how normal cells behave, how cancer cells behave.you know, deep sequencing, our ability to sequence a cancercell from an individual patient today in less than a week hasbeen dependent upon the decades
of the basic research. when you started taking thegleevec, what happened to that philadelphia chromosome? it just -- it went in thereand stopped that from growing. what percentphiladelphia chromosome? i went down to 5%in three months. i'm just letting peopledrink that in. this is exciting, excitingstuff. it is.
you're still on gleevec?orem: yes.i will be, probably, the rest of my life. if you were patient number,what, 9, to start, that probably makes you, if not the longest,among the longest -- i am the longest. the longest on.i have the title of "the gleevec queen," yes. is there a crown?[ laughs ]
yeah, this is the crown.see, i'm part of this crown right here. michael, you're partof a team now conducting trials on therapy for chroniclymphocytic leukemia, right? different kind of cancer. different kind of leukemia. what are you looking at? we have been working on anapproach that actually has been in the making for about20 years, and the approach
involves genetically engineeringcells -- patient cells, t-cells, in particular -- to make themspecific to target cancers. so the process involves takingt-cells from a patient -- removing them from the body --engineering them in some way, and then growing them in bags orflasks so that you have billions of those genetically engineeredcells, and then introducing them back into patients.essentially, we give patients an army of t-cells, which are oneof the main players of our immune system that targetsthe bad guys.
and what are you using tomake these cells? we are introducing the car,or the chimeric antigen receptor -- into t-cells with avirus vector. it is the skeleton -- a guttedvirus of the family of lentiviruses.and hiv also belongs to the family of lentiviruses. so it's an hiv-likeskeleton. exactly. and i want to point out,when the war on aids started,
a lot of the people doing thebasic research were oncologists. and this is why. exactly.the virus very, very potently can enter cells and integrateits dna into the genome, and that's just what we want to do.now, let me explain to you how it's been gutted, if you want,'cause it's important to understand.all of the molecules, all of the dna that encode -- that encodesall the proteins that the virus needs to multiply, to packageitself, and to infect
have been removed.it's just a skeleton. but that's ridiculous. it's fantastic! these are teeny-weeny,itsy-bitsy little -- of course it's fantastic.look at this man's face. look how excited he is. i'm excited, you're excited. papa: well, it's even moreexciting, because you're taking another scourge on the society,hiv, and you've somehow
convinced it to be a warrioragainst cancer. i think that's kind of cool. that's beyond cool.how are the results so far? what's going on? we have had some veryexciting results so far, treating b-cell malignancies.we have had profound success so far.we've treated -- initially we treated three patients with verylate-stage cll that had been -- the disease hadbeen refractory to every other
chemotherapy and treatment.two of those patients are alive today, two years later,with no evidence of disease by molecular means, so they are --we hesitate to use the "c" word, it's a very high bar, but we'regetting close to uttering -- but it's important withcll, because cll can be very chronic and go on for years andyears, for some of our viewers, they may say, "well, i couldhave had this for years." i think it's important to knowthat these were people who were at the end.
absolutely. they were expected to die.and as judy will point out and all of us will point out,early-stage clinical trials have to be done on patients that areat the very late stages of disease.you cannot offer them something that has the potential to causeharm, because we don't know, in exchange for something thatmight give them some quality of life. dr. kalos mentioned using amolecule, cd19, which was
engineered into a t-cell.you can also use that same approach by designing anantibody that has two business ends, if you will.one end is -- recognizes cd19, which is presenton cancer cells. chronic lymphocytic leukemia oracute lymphoblastic leukemia. at the other end is the businessend that will attract t-cells. so you form a bridge, and youinject this chimeric molecule into patients as an infusion.and very refractory acute lymphoblastic leukemia cells --patients with very advanced
disease -- about 60% of themwent into remission. there are smilingfaces here. there are smilingfaces, but as a primary care doc, this is very exciting inthe world of medicine, but for the individual patient right nowwho's very sick and has a very bad cancer, sometimes theirjudgment is skewed, and we've seen it a lot with some of thestem-cell stuff that's being done.there's a lot of research going on, and i think it's importantfor our viewers to know that
these are very well-trainedindividuals that have been doing this for years.there are less-than-savory individuals out there, like withstem-cell transplants, that will be happy to take your money todo something that they say he's doing, and it's not.all this stuff has to be in a controlled scientificenvironment. yes, absolutely. you know, that's critical.it's very important for patients to know that there arepeople who will take advantage
of you, and when you're sick andyou're at the end of your life, you're willing to say yesto anything. let's pause just for amoment and sum up where we've been, and we've been down a verylong road here. 40 years.and you're still with us. [laughs] yes.we've achieved significant victories in the fight againstcancer, and these are gains that have been made throughhealthier living, of course, and the work of health careprofessionals and clinical
researchers and thousands ofcancer patients, some of them at the end of the road,and their advocates and people working on all fronts.this is a world war. it's huge.and very expensive. billions and billions ofdollars, which we're going to have to continue to spend if wego forward. if we're going to spend thismoney, are these two successes that we've been talking aboutso far emblematic of what's going to come?or do we know?
are we going to win this war?and we're going to have to win it, what, piece by piece?what do you think? yeah, we're going to have towin it piece by piece -- again, because there'sno such thing as cancer, there's cancers, and we're going tohave to fight each one of them individually, is my suspicion.now, what we haven't really talked about today isprevention, and of course, a huge amount of the burden ofcancer in the united states is totally preventable.you know, we still have
tens of millions of americanswho smoke cigarettes. we still have all too manypeople dying of viral-induced cancers that are currentlypreventable with vaccines. we have a growing obesityepidemic, which we know is going to spill over into the cancerarea. so we, in addition to all ofthese therapeutic advances, we also need to add a whole lotmore in terms of prevention. and that's veryimportant, i think, also, because most of the stuff inmedicine, when you look at
the studies, 70% to 80%,interestingly, consistently, in these kind of retrospectivetrials, 70% to 80% of what happens to usis what we do to ourselves. and all of these treatments comeat a cost, because, you know, you'll hear people say,"i smoke, but they'll come up with something coming."they all have their down side. they all havesome collateral damage. you have to take a pill forever.you may have diarrhea. you may have to get, you know,i.v.i.g. infusions.
prevention -- you don't have todo that. i think the focus on earlydiagnosis is really important. i mean, prevention and ways toact in a healthier manner is obviously important.but it's still going to be a disease, and we still need to beable to diagnose it earlier. and i don't want to leave,judy, without asking you, how are you doing? i'm doing just great. well, you look great.
this has been a marvelouslife, you know, since then. it's a roller coaster at first,but since this, it's been fun. it's absolutelythrilling to see you here -- seeing this war play out andseeing one of the winners. yes. thank you. thank you for coming.it's not always easy to share a disease with the rest of theworld, and it was nice of you to join us.this has been a nice story to be able to tell.well, i want to thank
all of you forbeing here, but unfortunately, we're out of time.and i hope that you can continue the conversation on our website.there, you're going to find the entire video of this show, aswell as the transcript and links to resources.the address is secondopinion-tv.org.again, thanks for watching. thanks to all of you for beinghere, especially you. i'm dr. peter salgo, and i'llsee you next time for another announcer:
"second opinion."major funding for "second opinion"is provided by the bluecross and blueshield association,an association of independent, locally operated, and community-based blue cross and blue shieldcompanies. for more than 80 years,blue cross and blue shield companies have offered health care coverage in everyzip code across the countryand supported programs that improvethe health and wellness of individual membersand their communities.
the bluecross and blueshield association'smission is to make affordable health care available toall americans. news about our innovations is online at bcbs.comand on twitter @bcbsassociation.
No comments:
Post a Comment