This video features Henry Fung, MD, FACP, FRCPE presenting on Plasma Cell Dyscrasia. This presentation was given at our April 11th New Directions in the Diagnosis and Treatment of Hematologic Cancers Symposium in 2023.
Hello everyone. Thank you very much for joining us tonight. I'm Henry Fong from Fox Chase Cancer Center. I'm the professor and chair of the Department of Bone Marrow Transplant and Sterile Therapy at Fox Chase, not the director of Fox Chase Temple University Hospital B M T program. Today's uh my talk will be focused on the plasma cell disorder in particular, multiple myoma moral myoma. When I first started treating a patient with multiple myeloma not too long ago, it was around 30 years ago, we only have two drugs me and then we have, we ad most patients will not get given into a remission and most of them has a very brief survival. Survival is only about uh 2.5 years at the best. No F D approved drugs. But as you can see from this slide, and uh we have surprisingly the first F D approved drug for treatment of um A Moyo is a supportive care this phosphonate and this is a and then we have others uh over the past uh three decades. But as you can see the past few years is really explosive. See how many drugs has been approved which altering the natural history of the disease of patients with multiple melanoma. In our clinic, we now routinely see patients that are alive and well disease free for three years, five years, six years overall survival. We have seen patient 10 years, 15 years, one transplant, two transplants. And uh they have a free lines of therapy, six nights of therapy. So we have a lot of progress in model of my. Thank you for all the investigator and in particular, thank you for all the patients who are participating in the clinical trials making this a big difference. So there's a three core drugs responsible for the progress in multiple myeloma is that the inmate immuno moderating agent on the uh left hand side. And then we have the zone inhibitor and then now we have the N D CD 38 anti border. These free class of drugs has lead to significant improvement in the outcomes of patients with multiple my. And as you can see the slides on the uh right bottoms. Now we have 1/4 class of drugs targeting the BC MA, which we will spend some time to review the latest datas related to uh BC MA target therapy for patients with multiple. As we first start treating my, we give Melland Plazo two drugs and then we also have these multiple al lighting agent based regimens and then uh it's like a kitchen sink. We give all the algorithm agents that may work and put them together like ABC N U mouth land, uh Cytoxan, all different cocktail. None of them has been shown to be anything better. And then we move to V AD and then we have the inmate coming. We have the um Thom dexamethasone and then we have uh we have well K desole and then we moved to uh like a V T D and then have the L V D And now one of the most commonly used regimens for patient with Mo my Noma in the upf funded treatment setting. And in particular transplant eligible patient is L V D transplant has played a very important part for treatment of moral myoma. When I first do trans, when I first did transplant for moral myoma about uh 30 years ago, at that time, patient fails everything and high dose milland can overcome the chemotherapy resistant. Some patient with very uh refractory disease at that time can achieve some response. And unfortunately, on the other hand, there was a brief response until multiple clinical trials has showed the major benefit in particular progression, free survival and disease control. When used it at the upf funded setting. This is one of the latest phase free randomized studies. Um reported. This is the intergroup studies and started at Dana Faber Cancer Center and uh subsequently uh going to multiple cooperative group. This is the determination child. The phase three studied is comparing L V D alone versus R V D as up funded oop stem cell transplant. The most important message from this study is one transplant, work better up funded. And then you can see the median progression free survival is 5.5 years. In the old days, we will consider anyone progression free or remission for five years, a cure of their multiple meno or the any cancer. But now we can see the patients with R V D followed by out funded auto stem cell transplant at 5.5 years progression free survival and then overall survival in at five years, almost 80%. So this is a free drugs. I'll be the pool inhibitor and Dexone. And then now we are evolving to 1/4 drug with adding on A N D CD 38 antibody. As you can see from the table on the uh at the right hand side, border determination, child, the Griffin, child Griffin is comparing their R V D N D CD 38 anybody with R V D versus L V D in transplant eligible patients or patients receive a transplant. As you can see in a study, adding a uh N D CD 38 antibody better overall response, better V GP L better C L and better progressive free survive four years progression free survival, 87% versus 70%. So this four drug regimens is evolving as an important uh um combo or induction regimen for transplant eligible patients additions of the N D CD. 38 antibody to R V D, improved death of response and prevention, free survival in newly diagnosed transplant eligible patients which potentially ordering the natural history of disease. In one of the studies, the GMO 07 studies uh about 50% patient cannot even achieve AM R D negative after four cycles of uh N D CD, 38 anybody with R V D which may significantly alter the natural history of the disease for patient that transplant in all the mice studied. Now again, we are used to only give uh like a uh chemotherapy to non uh ineligible patient for and uh two drugs recommend that. And now we have three drugs. There are d as you can see on the left hand side, but free survival is almost five years better response in L V D, sorry uh in their R D versus L D and making this a preferred regimen at our program as well as endorsed by N C C N uh guideline and F D approved it as frontline treatment. Well, transplant ineligible patients complete mission is 51%. As you can see that this is also unusual to have any studies in autonoma to show your overall survival benefits. Because patient call over to the other arm, like in the study, the D arm, 48.5% received their treatment as any subsequent lines of therapy. And the cross over very difficult to determine and uh show a overall survival benefit. And here you can see an overall survival benefit. The next study is very interesting. 2017 oh three. I love this study because it's a study showing that. In fact, we can get a lower dose of dexamathasone for fail patients. We love that. The methadone is my best friend, is a hematologist, best friend, dermatologists, best friend. And, uh, when we don't know what to do, we give dexamathasone and steroid. And here really, we can cut down the dose. On the other hand, as we know that zero has a lot of side effects for failed patients. I think it may do more harm than good to the patient. Here, you can see the data has uh uh rapid is at least as good as ad and in fact, looks like even may be better. The overall response is 96%. We gp out 64%. The evolving data will maybe this will be really the best regimen for failed patients. As I promised earlier, we're gonna move to the anti PC ma car. The My PC MA is an antigen expressed specifically on plasma cells and my cells. It's a cell surface receptor of T N F superfamily and this is the target for multiple my noma and is the fourth class of drug. Now for multiple myoma, we have two car T cells uh uh approve it for treatment. Myoma BC ma and just remind you how we do car T cells. We collect the T cells uh insert the genes into the uh uh the T cells and uh expand the cells and uh the uh cells will express the uh antigens. And then uh we give the patient Lyr depressions in the car cells. The cart cell will expand the patient body and then would induced uh response and uh to the patients with advanced myeloma. And this is a cart treatment. The uh this is a uh slide showing you the efficacy of a cell and CTA cell. We should not do a uh really a comparison because we don't want to compare apple to orange. And some uh has claimed that one is better than the others. They have different uh um eligibility criteria and there are two different patient population. The most important thing is they both has very good overall response. 73% to 97% M R D negative, 39% for cells, 82.5% for CTA cells per person free survival, 8.8 months in a cell, 27 months for aceta cells. But I not a few things. There are more extra disease and uh I I did so and they are also more high risk fish and also the very poor response to uh pitching therapy in either cell five of only 112. And also the definition of relapse factory different cta cells. Progression less than equal to 12 months after the last line of therapy and ID cell progression less than equal to 60 days after the last line of therapy. Superficially, I think the CTA cells is definitely better than I cell superficially only because this is different patient population. Both drug looks very good to me. And for a patient with advanced factory in multiple meno overall survival about two years compared with other drugs available for salvage. As you can see in the mamma study is a retrospective study. The media overall survival is only eight months and Alexa and about eight months in the strong studies and then wrapped which is currently out of market. Uh is ABC M ABC MA antibody drug conjugate and overall survival is about a year. All of these has a overall response about 30% here. The BC MA caught himself as however limited by cytokine relief syndrome. And the great then you go to 37% for either cell, 4% for CTA cells. And also uh with all the cardi cell we use for our uh in our program, we have performed about 70 cardi cells over the past few years. We really now learn, know how to do this and uh monitor the side effects. And many of the patients, we also do it completely outpatients and new toxicity is another major toxicity that we need to monitor them closely. They are potentially life threatening and evolving Another B semi type of therapy is by specific antibody which also uh bind to the CD three on the T cells which engage the T cells leading to lies of the uh my cells. The Lister Ma is the first uh by specific antibody type ABC ma approved by FDA. As you can see here, most of the patients failed to multiple uh multiple regimen paraly B five triple cost exposed 100% panna exposed 70% with factory to last life B almost 90%. And amazing. I it's difficult to remember all the details but I remember this like overall response, about 60% complete remission, about 40% M R D negative about 20%. It's very promising overall response. And so far we have treated about 15 patients, almost every one of them have some response, but it's too early to determine in our own experience because we just start using it in late December last year. But the downside is the Cytokine Relief syndrome. We need to monitor closely to these patients. Although grade three is only less than 1%. But overall all grade C out 72% and new toxicity. Most severe, most common one is headache. I can only 3%. So percussion free survival about 11 months. And I think this is another major addition to patients with advanced factory multiple my noma. Oh unfortunately, as you can see, they have no and they need additional treatment when they relapse. And uh when we consider the Lister map, we also need to notice that in order to mitigate mitigate the side effects with C L S, it was given as a, a step up dosing. And it is recommended that this be given the inpatient and patient should be hospitalized for 48 hours after administration in the packet in is that day 147 impactor, we admit the patient day 135 and discharge them on day seven. And then uh because uh of the C L S and uh new toxicity, we always need to monitor, monitor them closely. And in our program, we also the uh start uh a selecting a patient with uh receiving by specific anybody going into our outpatient party program when they failed. I think uh really they have very limited treatment or they have no option. Much kidney trial is always the best treatment and this is a very promising uh new uh coming for patient with. Uh we left refractory model meno G protein coupled receptor class C group five D by specific antibody. About 10 patients have P PC MA exposure. They can still demonstrate it with 100 45 patient study overall response of 73% progression free survival of almost one year. Again, they have significant CL S uh but most of them are grade 12. And then we also have the same anti G PR C five D T cells. Again, that patient that has failed BC MA type of therapy, as you can see here and the bar chart that have nine patients failed BC MA B four and with a complete remission of 44%. This will be another new addition to patients with uh advanced refractory model. My, in summary, we have evolved to four cast of drop in inhibitor, any CD, 38 any anybody. And uh now has PC MA have a further B and we have our friend me with us. Car T cells immunotherapy N E CD through the antibodies we have by specific antibody. And this is good news for our patient and also making this a water compact and complicated treatment for patients with multiple meno. Thank you very much for your attention.