Rina Patrawala discusses newly FDA approved indications for existing hematology/oncology medications as well as newly approved treatment options for various oncologic malignancies. Jane Rogers discusses newly FDA approved indications for existing hematology/oncology medications as well as newly approved treatment options for various oncologic malignancies.
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Okay, everyone, I'll go ahead and introduce our next speakers for our next topic, where we're going to go over our pharmacology update. I'd like to introduce Jane Rogers. She is a clinical pharmacy specialist at the University of Texas and D. Anderson Cancer Center in Houston, Texas. Dr. Rodgers earned her doctor of pharmacy degree in 2000 and eight at West Virginia University School of Pharmacy in Morgantown, West Virginia. She went on to complete an A S H P accredited pharmacy practice residency at West Virginia University hospitals in Morgantown, West Virginia, and an A f A S H A H P Accredited Pharmacy oncology residency at the University of Texas, MD. Anderson Cancer Center in Houston, Texas, in 2000 and nine and 2010. Respectfully, um, you have quite the alphabet after your name, so I'm I'm sorry. I'm messing it up, but I wanna be good about it. Here, Um, she's a board certified. She is board certified in Oncology Pharmacy and currently works in the Gastrointestinal Medical Oncology Clinic at the University of Texas MD. Anderson Cancer Center in Houston, Texas. Her partner, speaker today eyes also Rina Petro Allah. She is a supervisor of clinical oncology pharmacy services at Scripts MD. Anderson Cancer Center. She is a graduate of the Ernest Mario School of Pharmacy at Rutgers University in New Jersey. She completed a pharmacy practice residency, followed by a specialty residency and oncology pharmacy practice focusing on blood and marrow transplantation at the University of Illinois at Chicago. She spent four years at the University of Illinois at Chicago Medical Center, followed by an additional three years at the Sydney Kimmel Cancer Center at Thomas Jefferson University Hospital and the Hematology and Blood and Marrow Transplant Division. Respectfully, respectfully, respectively, she moved to scripts. Health in 2006 is an advanced practice pharmacists and oncology and transport transplantation, and moved into an oncology clinical pharmacy leadership role after the creation of the scripts M. D. Anderson Cancer Center Partnership. Thank you both, and we look forward to your presentation. All right, Well, thank you, Bora, for that introduction and good morning, everyone. Um, arena and I will be going over new approvals since October 2019 to October 2020. Um, going over new indications for drugs already on the market and going over new drugs to the market through a presentation. So a lot of drugs to get through, which is great, because we had an exciting year here. Um, we have split our presentation into solid tumor updates and liquid tumor updates. So I'm gonna be going over the solid tumor updates. Mhm. I have nothing to disclose regarding this presentation. And so to start, we'll go over new indications for drugs already on the market. We had a lot of immunotherapy indication of dates. Um, thanks, uh, with regards to this year. So Nivola mob saw, um, and indication for under a spectacle malignant pleural mesothelioma in combination with balloon a mob. It also was approved for unrestricted ble advanced recurrent or metastatic esophageal squamous cell carcinoma after flora permitting and platinum based chemotherapy. First line treatment for patients with metastatic or recurrent non small cell lung cancer. Um, in combination with the balloon. A mob with no e Jafar al Genomic. Two more operations in the patient. And it also received an approval for her Peto cellular carcinoma in patients previously treated with Saraf active in combination with balloon A mob, it balloon mobs. New approvals coincide with the ones I already mentioned with novel a mob in combination devil. A mob received a new additional approval for combination with the TOPE aside and either Carbo Platon or CIS Platon as first line treatment of patients with uh squamous cell lung cancer. Tessa Lose a MAB received approval for combination therapy with Kobe Menem and demure affective and patients with your FB 600 mutant positive unrestricted war metastatic melanoma. It received approval in combination with Davis's mapas front line therapy for Unrestricted War Metastatic. Compared to cellular carcinoma, It received approval for frontline treatment of adult patients with metastatic non small cell lung cancer whose tumors have specific PD l one expression and then they don't have any e Jafar al genomic tumor operations. And it also received approval in combination with paclitaxel, protein bound and carbo Platon. For the first line treatment of adult patients with metastatic non small cell lung cancer, again without E g f R OUT tumor operations Pemper lose a MAB received frontline treatment approval for unrestricted or metastatic colorectal cancer patients who have micro satellite instability, high disease deficient mismatch repair chambers. Symbolism have also received approval for metastatic cutaneous going to cell carcinoma that's not curable by surgery or radiation. And it received approval for adult and pediatric patients that have unrestricted war metastatic solid tumors that have a high tumor mutation burden. UM, that have progressed following prior treatment and have no satisfactory alternative treatment options. And lastly, it received approval for BCG unresponsive, high risk, non muscular, um, bladder cancer. Um, in patients that Aaron ineligible or not elected to undergo suspect. To me, there were some other approvals outside of immunotherapy. Eso Ramus your mob received an additional approval for combination with their latinum for first line treatment of metastatic non small cell lung cancer with specific e g F R mutations or deletions. Elaborate have received approval. Um, surrounded by germline mutations in tumors, cast rate resistant prostate cancer and ovarian fallopian tube and primary peritoneal cancer and pancreatic cancer. With specifics that air written here on the slide um, Pamela Hmeid received additional approval for patients with AIDS related Kaposi's sarcoma after failure of highly active antiretroviral therapy and Kaposi's sarcoma and adult patients who are HIV negative made a mason had an additional approval for low grade upper tract, your ethereal cancer in Carafa. Nip received approval in combination with the Taksim, Um, for patients with metastatic colorectal cancer that have a be roughly 600 a mutation that have received at least one prior therapy. Mhm recap. Rib received approval for Brack and mutated metastatic castrate resistant prostate cancer who have progressed on certain therapies. Europe Rib received approval for a pithy liel ovarian fallopian tube and primary peritoneal cancer. Um, in specific circumstances, Nurettin IB received approval for patients with advanced or metastatic, her two positive breast cancer who received two or more prior anti her two based regimens in the metastatic setting in Saluda Mine, UM received approval for metastatic castrate sensitive prostate cancer and for granting him received additional approval for patients without positive metastatic, non small, So long cancer. So a lot of new indications, so to start talking about our actual new drugs to the market will start within for two mob, the doi eaten um, it was approved in December 2019. Its's was approved for adults with locally advanced or metastatic, your ethereal cancer, previously given anti program death one or anti program death, one Ligon inhibitors and a platinum containing regimen. It's a fully human monoclonal antibody, directed at next in four in combination with the micro tibial inhibitor called M M A E conjugate. It's dosed at 1.25 mg per kilogram, given as an I V infusion over 30 minutes on days 18 and 15 of a 28 day cycle as faras renal adjustments and hepatic adjustments. There's no none for renal adjustments. However, they do recommend to avoid and moderate to severe hepatic impairment due to no data. For that, it does contain some drug drug interactions, so there should be reviewed prior to starting therapy due to the microbial inhibitor portion of the drug, the adverse effects are listed here. Most common fatigue peripheral neuropathy. The nausea, vomiting risk appears to be a moderate amenah genic risk agent. They recommend certain monitoring and warning precautions such as hyperglycemia, closely monitoring that and patients at risk for diabetic ketoacidosis watching for peripheral neuropathy and ocular disorders, the prescribing information recommends to consider prophylactic artificial tears. They can have skin reactions on this drug, such as macular popular rash or Prue rightists, and can sometimes have infusion site extra visitation. The next drug is FAM Trust. Choose a mob directs to can uh, it was approved and also December 2019. For adults with UN respectable or metastatic, Her two positive breast cancer previously given two or more prior anti her two based regimens in the metastatic setting. Its target is her to with the directed antibody that is humanized and in combination with the Tober I som raise one inhibitor. The dozing is 5.4 mg per kilogram i v infusion every three weeks and as faras renal in a paddock adjustments. There's no data for severe impairment in either of those, and they recommend for moderate hepatic impairment to monitor for increased toxicities. Given its humanized nature, the first infusion is given over 90 minutes and then subsequent infusions were given over 30 minutes. Right? Three adverse effects again are listed here. Um, the nausea vomiting risk for this agent looks to be moderate. Um, due to that toe Bryce Ahm race inhibitor component, it does have some monitoring. A morning precautions, including interstitial lung disease to monitor for is 9% of breast cancer patients in the study had this, um recommend to following for Milosz oppression and left ventricular dysfunction have a pretty enemy is our next drug. It was approved in January 2020 for adults with UN respectable or metastatic gastrointestinal stromal tumor harboring Ah platelet derived growth factor. Um, mutations. And it's a kindness inhibitor that targets these mutations. The dozing is 300 mg by mouth daily on an empty stomach and regarding Reno in a paddock. Adjustments. The safety has not been established with severe impairment, and either of them, and it does carry drug drug interactions. The average effects are again listed here to point out a few, um, it can cause a Dema cognitive impairment. Nausea, vomiting risk looks to be maybe a high to moderate Orel Meta genic risk agent um, regarding monitoring and warning precautions. It's recommended toe watch for intracranial hemorrhages that occurred in 1% of the patients seen and to watch for central nervous system effects that appeared to occur pretty frequently enough of 60% of the patients. And these could be cognitive impairment. Dizziness, sleeper mood disorders. Um, it looked to be that very rarely patients had to discontinue the drug due to these effects, but should still be monitored, so less than 5% had to discontinue the drug do that, but something that's a bit unusual, so something to follow. The next drug is Tess Meta Stat. It was approved in January 2020 for patients greater than or equal to 16 years old with metastatic or locally advanced epithelial sarcoma not eligible for complete resection. It also has approval for adult patients with relapse refractory follicular lymphoma, whose tumors air positive for an easy H two mutation and previously given at least two prior therapies or who have no satisfactory treatment options remaining. It's a method transfer ace inhibitor of Easy H two and some easy H to gain of function mutations. And the dozing is 800 mg by mouth twice a day, with or without food, Uh, renal, no renal adjustments. And for hepatic, it's not been studied in moderate or severe hepatic impairment. It does have drug drug interactions. So, again, something to review prior to starting the medication adverse effects. Um, it appears to be a low to minimal and meta genic risk agent. The adverse effects are listed here based on what was seen in the study, which does point out a point to always look at what cancer you're using this drug in as a lot of these drugs will be studied in multiple different cancers and often times. Sometimes the adverse effects don't necessarily match up. Just depends on the malignancy at times. So the things to monitor for our CBC with differential and to watch for secondary malignancies as T cell lymphoblastic lymphoma has been seen, UH, myelodysplastic syndrome and acute myeloid leukemia in less than 1% of the patients moving on to our next drug is So you met in in it was approved in April 2020 for pediatric patients greater than or equal to two years old within F one who have symptomatic, inoperable plexi form neurofibromatosis. The kindness in him. It's a kindness inhibitor of magen activated protein kind is one and two. The dozing is based on body service area, so 25 mg per meter squared by mouth twice a day on an empty stomach. And for renal adjustments, there are no adjustments. And for her paddock adjustments, uh, it's recommended in moderate hepatic impairment to adjust, and it does have some drug drug interactions. Yeah, with regards to side effects that does appear to have maybe high to moderate meta genic potential for an aural agent. Other side effects listed and monitoring. Morning precautions include cardio myopathy, ocular toxicity, gastrointestinal toxicity, specifically diarrhea. Watching for increased to creating fost food kindness and watching for rhabdomyolysis symptoms. There's vitamin E in the capsule, so they have a potential for increased vitamin E levels and a risk for bleeding due to that potential. And it's recommended to monitor for liver function tests with this drum. Next step is to Cabinet. Also approved in April 2020 it was approved for adults with unrestricted bore metastatic. Her two positive breast cancer, given in combination with trust, is a mob and Capeside of being in patients that have been previously given at least one prior anti her two therapy. It's a kindness inhibitor directed at her to the dozing is 300 mg by mouth twice a day, with or without food. And the adjustments for renal adjustment is it's not recommended, um, in severe renal impairment, most likely because given in combination of Capeside of being, which is not recommended in severe renal impairment and hepatic impairment, it has adjustments for severe hepatic impairment. It does have several drug drug interactions that should be again reviewed before starting the drug for adverse effects it looks to cause diarrhea. Hand foot syndrome was reported, however, most likely related, probably to the caves side of being nausea, fatigue, PATA toxicity eso monitoring on warning precautions are for diarrhea, which was common and seen in about 80% of patients and, um, Hoppenot toxicity, which was seen in about 8% of patients. It looks to be a load of minimal meta genic brisk agent. Next up is Pima Gotten In, which was also approved in April 2020. It was approved for adults with previously treated un respectable, locally advanced or metastatic Colangelo carcinoma that have a fibroblast growth factor receptor to fusion or other rearrangement. And this drug is a kind of inhibitor that targets F G F R 12 and three. It's dosed 13.5 mg my mouth once daily with or without food for 14 days on than seven days off. And it's not been established for severe renal or severe hepatic impairment, and it does have drug drug interactions. Adverse effects. Um, common with this class of drugs is to see hyper Fosca tenia and nail changes. Um, with regards to the hyper Fosca tenia also in the study, they found Hypo Fosca tenia likely as potential for overcorrection of treating the hyper Fosca tenia the monitoring and warning precautions. Um, for this drug is for watching retinal pigment epithelial detachment that occurred in about 6% of patients and hyper fost patina is already alluded to as that's very common side effect occurring about 90% of patients and the prescribing information has, uh, specifics on when to start lowering uh, phosphate in taken diet and also went to initiate a low phosphate binding drugs. The Amenah genic risk for this agent appears to be low to minimal. Mhm. Next up is Tacitus Mob Go Veta Con. It was approved in April of 2020 for adults with metastatic triple negative breast cancer. Previously given at least two prior therapies for metastatic disease, it's a humanized monoclonal antibody targeting stroke to and in combination with the toe price armories inhibitor. It's those 10 mg per kilogram ivy. Once weekly days, one in eight of a 21 day cycle for renal in a paddock adjustments. There is no information for severe renal impairment or for moderate to severe hepatic impairment. It's recommended to pre medicate with anti medics and H one and H two blockers prior to giving this drug. The first infusion is over three hours and 1 to 2 hours for subsequent doses and to monitor the patient during the infusion. And for 30 minutes after the infusion, it does have the potential for drug interactions due to the toe price on race inhibitor portion of the drug for adverse effects, it appears to be a moderate, a meta genic risk agent. You can see neutropenia diarrhea, which coincides with some of their monitoring a morning precautions to watch for severe neutropenia. Severe diarrhea may occur hypersensitivity, nausea, vomiting and noted in the prescribing information where patients with UGT one a one Hamas, I guess, deficiency that those patients can be at an increased risk of neutropenia. However, those adjustments weren't really, uh noted. That's right. Theme. Next drug is Kevin Matin in. It was approved also in April 2020 for adults with metastatic, non small cell lung cancer whose tumors have a mutation that leads to met Exxon. 14. Skipping the It's a kindness inhibitor that targets met, and it's doses 400 mg by mouth twice a day, with or without food and no data for severe renal impairment and, UM, no adjustments for hepatic impairment. And it's recommended again to review medications as there's some drug drug interactions with this drug as well for adverse effects. Um, you could see peripheral oedema, nausea, vomiting, fatigue, dips, NIA and decreased appetite. It looks to be a low to minimal meta genic risk agent for monitoring and precautions toe watch for interstitial lung disease and Newman itis, which can occur in about 5% of patients and monitoring for her padded toxicity. Azaz increases in liver function tests were seen and photosensitivity next up, a cell for Captain in, uh, it was approved in May of 2020. Um, it has indications for adults with metastatic refuge in positive, non small cell lung cancer and also for patients greater than or equal to 12 years of age with advanced or metastatic red mutant medullary thyroid cancer who require systemic therapy and with advanced or metastatic refuge in positive thyroid cancer who require systemic therapy and who are radioactive iodine Refractory. The way the drug works is the kindness inhibitor that this wild type, red and multiple mutated red is a forms the dozing is dependent on how much the patient ways. But it's a twice a day medication given with or without food and no data for severe renal impairment and for Hispanic adjustments. It's recommended to adjust the dose for severe panic impairment. And there are some drug drug interactions and particularly noting, um, in addition, Thio inhibitor drug interactions. There also is an interaction with acid reducing agents, particularly proton pump inhibitors and her two blockers. Onda package insert has specifics on If you can't avoid the combination of these drugs there specifics on how you administer the medication If you can't get the patient off of the P p I or her to blocker as faras adverse effects um listed here is elevations in liver tests, which coincides with monitoring for a padded toxicity can cause hypertension. Um, que t prolongation hemorrhagic events. Hypersensitivity and risk for impaired wound healing. So it's recommended toe. Hold the drug at least one week prior to elective surgery and to not a minister for at least two weeks after major surgery or until the adequate wound healing has occurred and it appears to be a load of minimal meta genic risk. Agent repetitive is was approved in May of 2020 for adults with advanced gastrointestinal stromal tumor Previously given three or more kindness inhibitors, it's a kindness inhibitor that inhibits kit and platelet derived growth factor receptor A. It's does 150 mg by mouth daily, with or without food and no data on severe renal impairment or moderate to severe hepatic impairment use. And it does contain drug drug interactions. The side effects are listed here. Um, the meta genic risk looks to be low to minimal. Does recommend to monitor for cutaneous squamous cell carcinomas is those were seen in about 5%. Hypertension was seen in about 14% of patients. So something to monitor for a zealous cardiac dysfunction and risk of impaired wound healing. Again holding a drug. This drug requires that for one week to be held prior to elective surgery and to not a minister for at least two weeks after a major surgery. Next up is Luber Next tin. It was approved in June of 2020 for adults with metastatic um, small cell lung cancer with disease progression honor. After platinum based chemotherapy, it eyes an apple aiding agent. Those that 3.2 mg per meter squared ivy every 21 days. Given over a 60 minute infusion, it could be given central or peripheral line. However, there are specifics about different DELIA. One amounts in the prescribing information, depending on what access you have for the patient. For renal adjustments, there are none for her. Paddick adjustments. There's no data for severe moderate paddock impairment, and it does have drug drug interactions. Ast faras adverse effects. Um, watching for Milo, suppression is recommended. And for her patio toxicity, it looks to be a moderate. A meta genic risk agent um mhm. And the next drug is pertuzumab plus tries to use a map in a subcutaneous form that was approved in June of 2020. Um, it is approved for combination with chemotherapy as new adjuvant treatment for her two positive, locally advanced inflammatory early stage breast cancer as treatment. Azad event treatment for her two positive early breast cancer at high risk of recurrence and his metastatic treatment, her two positive naive um, or chemotherapy for metastatic disease. It targets her to buy the pathways that purchase a map. Does this and trust use a map? Does this separately just depends on the domains that they target the dozing and, um, an administration. The dozing is different than the Ivy form. Um, it's recommended as an initial dose sub Q to be given over eight minutes and then maintenance doses are given sub Q over five minutes every three weeks. The subcutaneous You should only be in the thigh, and it does have drug interactions for anthro. Cycling therapy. Um, I think we're missing a slide here, but the side effects for this drug are similar. Thio the side effects of pertuzumab and trust who's mad when they're used separately? Um, should be a low, minimal risk, low to minimal meta genic risk agent and the injections. Air only recommended, um, to be given by health care professionals because of potential for hypersensitivity, as patients should be monitored for about 30 minutes after the first injection and then for maintenance injections at least 15 minutes, and then my last drug to go over his palace, Sittinin. It was approved in September of 2020 for adults with metastatic refuge in positive, non small cell lung cancer. It's a kindness inhibitor of wild type Rhett Uncle genic Rhett fusions and red mutations. The dozing is 400 mg by mouth daily on an empty stomach and for Arenal in a paddock. Adjustments. There's no data for severe renal impairment or for moderate to severe hepatic impairment. And it does contain drug drug interactions. Adverse effects looks to be a low to minimal Amanda Genic risk agent. Most common are listed here. Need to follow for hypertension is about 30% of patients saw elevations in their blood pressure watching for her patio toxicity, interstitial lung disease and pneumonitis him a Rogic toxicity and has also the risk for impaired wound healing. So they recommend to hold at least five days prior to elective surgery. And it released two weeks following major surgery. Okay, And with that, I will pass this on to arena to discuss human geologic malignancy updates. Good morning. My name is Rena Patch Walla. Thank you, Jane. Jane definitely had the bulk of the FDA approvals. The cycle eso Thanks for all of your work on the solid tumor updates. Um, I will, as Jane, um, has spoken. I will be going over the human logic malignancy updates this morning. Um, so 77 issues here. Okay. In terms of faculty disclosures, I have nothing to disclose this morning. So first I'll be going over our newly approved expanded indications in the last year for products which are currently commercially available. Besides existing FDA approved indication for Mantle solemn Foma, the second generation beat B t K inhibitor a collaborative is now FDA approved for the treatment of CLL. Where S l l dare to mob is now FDA approved to be used in combination with car fills a mob plus Dex Smithson for relapse refractory multiple myeloma in patients who have received at least one previous line of therapy. Besides the large plethora of existing FDA approved indications, which Jane went over as well, pay Embolism AB is now also FDA approved for relapse refractory classical Hodgkin's lymphoma in adults after front line therapy. A swell as in Children after two plus lines of therapy, Uh, Salon X or, aside from the existing FDA, approval for multiple multiple myeloma is now FDA approved for relapse or factory diffuse large B cell lymphoma not otherwise specified. This includes lymphomas arising from transformation after two plus lines of therapy and I. Bruton, it is now FDA approved in combination with the tux. A map for upfront treatment of CLL or S L l Okay, um, so moving into Zana brute neb. This is now FDA approved. It was FDA approved in November of 2019 for adults with mantle cell lymphoma who have received at least one prior line of therapy. Um Zana, Britain. It is another second generation B t K inhibitor, which has the same mechanism of action as I brute nib, um however has a decreased risk of bleeding events. Um, and nuance said atrial fibrillation compared Thio, the first generation BDK inhibitor I brought him. Um, the dose can be taken with or without food. It's available as 80 mg capsules. Eso you patients can take two capsules 160 mg early, twice a day where four capsules. Um, 80 mg. I'm sorry. 320 mg daily. Um, instead, Um, in terms of dose reductions, um, does productions are based on grade three or higher? Nonhuman logic toxicities. Great three Febrile neutropenia. Great. Three. Thrown aside. Pina with significant bleeding or grade four neutropenia lasting greater than 10 days or great for thrown aside. A pina lasting greater than 10 days, so the dose reductions are is listed here for the first occurrence of Texas City. You would interrupt, then resume at full dose for the second occurrence. You would decrease the dose to 80 mg B i D or 160 mg daily for the third occurrence. You would interrupt, then resume at 80 mg daily. Um, and if there would be 1/4 the current, she would discontinue completely in terms of dose reductions recommended for Mel to moderate riel impairment, there is no dose reduction recommended. A swell. As for hepatic impairment that is mild to moderate. Um, for severe renal impairment, it's only recommended thio increased monitoring for those patients. And for severe hepatic impairment, you would reduce the dose to 80 mg twice a day. Uh, in terms of drug drug interactions and a brunette is primarily metabolized by the cytochrome p 4 50 a enzyme. So therefore, when given concomitantly with 38 inhibitors such as Clara Throw Meyssan, Aretha Mason, Delta Zamora, Chicana ZOLL, um, it would be recommended to rid reduce the dose. The starting dose of Zana Bruton head for three inducers, such as rampant. The recommendation is to avoid if possible as it decreases are reduces the A C by approximately 90% of Zana Bruton ipso thereby UM, causing it to be pretty much ineffective in terms of adverse events. The most common would be set up India's as well. Azaz Respiratory tract infections You need to go back one. It's right. Restaurant infections. Um, rash, bruising and diarrhea. Most common great 3 to 4 lab abnormalities. That air scene. You can see a decrease in neutral account platelets, hemoglobin and potassium levels. A swell as an increase in the lymphocyte. Count your gas levels. Lt. And Billy Rubin, uh, for monitoring and warning warnings involved with this medication. This medication does cause hemorrhage on DSO. Most of these bleeding events were a great three or higher included, uh, intracranial G I he Manchuria in in hemothorax. Um, however, we're only reported in a small number of patients, approximately 2% for patients undergoing surgery. You would make a risk benefit assessment on do what you would consider withholding for 3 to 7 days pre and post surgery. Um, this would depend upon the type of surgery and the bleeding risk associated with that surgery. Um, also, if you are co administering with anti platelet agents or anti coagulants, you may further increase the risk of hemorrhage. Um, infections did occur in patients grade three or higher occurred in about 23% of patients, Um, and most commonly that was reported as pneumonia. Um, there have been cases of hepatitis B viral reactivation onder. There is a consideration for possibly profile axing against HSV in P J P as well as other types of opportunistic infections. Um, in terms of malignancy occurred in about 9% of patients and was primarily reported as skin cancer. Um, arrhythmia has occurred in about 2% of patients grade three or higher, only about 0.6% of patients. So the recommendation is to monitor for signs and symptoms, especially in patients with risk factors such as hypertension or patients with high fevers related to infection. The next product I'd like to talk about is is a Texan map. This was FDA approved in March 2020 for use in combination with Pamela Hmeid and Decks, a meth sewn in multiple myeloma. In patients who have received two prior therapies, the prior therapies must have included little item ID and a producer. I'm inhibitors such as brutalism ib. The mechanism is that it is a CD 38 directed antibody, Um, and which is primarily expressed, are highly expressed on malignant plasma cells. Um dozing and administration cycle one. You'd be dozing on 10 mg per kilo i v infusion on days 18 15 and 22 of a 28 day cycle cycle two onwards. You would be administering same dose, 10 mg per kilo. I the infusion on days one and 15 so every other week of a 28 day cycle it is recommended to pre medicate these patients 15 to 60 minutes prior to infusion eso in terms of pre medication uh, decks, um Episode 40 mg i. V. Europeo or 20 mg If patients are greater than equal to 75 prior to therapy acetaminophen 652,000 mg Pio Um, in h two antagonist, for example, for Modine on diphenhydramine 25 to 50 mg i v. Europeo ivy is actually preferred for the first for infusions of this medication. In terms of infusion rates, this is another medication where we do a stepwise titra Asian eso for day one. We start at 25 MPH for 60 minutes. If there's no infusion related reactions, we can increase by 25 MLS per hour every 30 minutes to a maximum of 150 MPH. For date, we can start at 50 MPH for 30 minutes, increase by another 50 MLS per hour 10 30 minutes, and then can increase to 100 MPH every 30 minutes to a maximum of 200 MPH. From day 15 onwards, you can just start at the 200 MLS per hour infusion rate. In terms of renal and hepatic adjustments, there are none on. There's really no clinically significant drug drug interactions. There are, however, some significant lab interactions because CD 38 is widely president on red blood cells. Um, it may giving this medication may result in false, positive indirect Coombs test, so it's very important that you type in screen patients before the first fusion of this medication. Um Tau and tau also notify the blood bank that this patient will be receiving this medication. It's a text map is also an I G Kappa monoclonal antibody that can be detected on both serum protein electrophoresis and immuno fixation essays, which we use for clinical monitoring in multiple myeloma. So this can impact the accuracy of determination of CR in patients with I G Kappa myeloma in terms of adverse effects. Again, the most common we've got neutropenia infusion related reactions, pneumonia, upper respiratory tract infections and diarrhea for monitoring and warnings. Um, for infusion related reactions, 39% of patients had infusion related reactions. And, um, 98% of patients had them during their first infusion. Thankfully, most of them resolved with that first infusion. Again, the recommendation is Supreme Medicaid to decrease the risk and severity of these reactions. So for a great one or two infusion related reactions, recommendation is to interrupt. Once improved, you can restart at half the initial infusion rate. If symptoms do not recur, you can increase um to the initial rate and then increase sequentially according to the prescribing information. If the patient has ah great three or higher adverse infusion reaction, the recommendation is to permanently discontinued treatment, and if symptoms do not resolve or they recur after or they recur after interruption again, the recommendation is to permanently discontinue treatment in terms of neutropenia thes, 96% of patients had neutropenia, 85% son of patients had great 3 to 4 neutropenia and febrile neutropenia occurred in about 12% of patients. So it is recommended to do a CBC with differential prior to initiation. And prior to each dose, um, secondary malignancies did occur in patients, um, at at about a rate of 4% um, and again, keeping in mind, the lab tests interference important to type and screen patients prior to starting treatment on but to inform blood banks that patients are receiving this treatment and again important to consider the embryo fetal toxicity in patients who may be, um, considering pregnancy. The next medication that will talk about was FDA approved in May 2020. This is Dara Team a mob in combination with highly Rana days. Um, this is FDA approved in combination for multiple myeloma patients with V M P and newly diagnosed patients that were not eligible for an autologous stem cell transplant in combination with our T. I'm sorry R D in newly diagnosed patients that Aaron are eligible for an autologous stem cell transplant and in relapse refractory patients, um, with one prior therapy, also in combination with V D with one prior therapy. Um, it's also FDA approved as monotherapy with at least three prior lines of therapy on bond. Those prior lines had thio have included a pro deism inhibitor and an imminent modulate torrey agent. The mechanism of action is that it also targets city 38. Um, initial dozing and subsequent dozing well depends upon the indication. So whether it's used in combination with those specific regimens as mentioned above or in monotherapy, eso would be 1800 mg of dare to mob given subcutaneous Lee over about 3 to 5 minutes. It's given weekly Onda again. The number of doses will vary, depending on indication, and then subsequent doses are given every 2 to 3 weeks on Ben Q. Four weeks thereafter. Um, the subcutaneous administration should be in the abdomen on, but it is a should be given approximately three inches to the right or left of the naval. Um, it is important to pre medicate these patients at least 123 hours prior to each dose. Aziz. Well, as's to post Medicaid, these patients, um, pre medications are again the usual suspects of acetaminophen. Diphenhydramine a swell as a steroid, um, steroid dose will differ if you are using it. Aziz either monotherapy or using it in combination. If one of your combination treatments does include a steroid, you can admit the steroid pre medication here. For post medication again, the dose will differ, based on the indication that you're utilizing it for, um, but typically consists of metal pred 20 mg, either one or two days post treatment. Um, if there's no reported systemic reactions that occur after the first three doses were given, you can actually considered leasing the steroids altogether. In terms of renal and hepatic adjustments. There are non with this, um, agent. And there are no clinically significant drug drug interactions. Lab interactions similar to its attacks map that we spoke about earlier. Um, it can interfere with serological testing on did with determination of CR in patients with I G Captain Mile on them. So adverse effects again. Most common with monotherapy, we've got respiratory infections as well. Asai Pena's most common in combination with the MP constipation, nausea, neuropathy, diarrhea, insomnia, vomiting and fatigue. Most common common in combination with R D is fatigue, diarrhea, spasms and constipation. In terms of the monitoring and warning precautions, Um, administration reactions can occur in up to 11% of patients. Um, Grade two occurred in about 4% of patients grade through Grade three occurred in about 1.4% of patients. Um, most of those administration reactions occurred with the first injection approximately 10%. Um, there were smaller percentages, 0.2% that occurred with second injection and then, um, cumulative cumulatively, 0.8% with subsequent injections. Um, the interesting thing about these reactions is that the median time to onset was 3.7 hours on DSO. It wasn't an immediate reaction that you saw, however, delayed reactions, you know, days delayed occurred in less than 1% of patients. So it is important to monitor these patients, especially after the 1st and 2nd injections, and for great for which would be enough lactic type to permanently discontinue local injection site. Reactions were reported primarily era thema, and we're managed with symptomatically um, neutropenia from inside a pina again, consider withholding until recovery of counts, and it is important to do a CBC with differential prior to initiation and with each dose, um, and again just toe. Recommend the lab interference, making sure that you type in screen patients prior to starting treatment and informing blood banks. That patient is receiving this therapy and important to consider the embryo fetal toxicity of this medication. Okay, the next medication that was FDA approved was decided being in combination with Sad as your dean, Um, this was approved in July of 2020 and it's for adults with myelodysplastic syndrome. This includes previously treated untreated de Novo and secondary MDS. Subtypes are a R s r a b and C m m l an intermediate one intermediate to and high risk I pss groups Mechanism of action is ah, hype, hype, methylation of DNA. Um, in combination with a cited cited Dean D'Antoni's inhibitor. Um cited Deion dominates is actually an enzyme that catalyze is degradation of cited Dean analog, including decided being, um, it's found in high levels high levels in the G I and liver. Um, this is actually what limits the aural by availability of, um decided to being and so giving it in combination increases the systemic exposure of aural decided being dozing administration. Um, it is recommended to take on an empty stomach. We recommend patients not consume food two hours before or two hours after. If patients do miss a dose, they can. You can extend the dozing period by one day for every missed dose to make sure that they complete the five daily doses. Eso the recommended dose ng is one tablet daily days, one through five every 28 days until disease progression or unacceptable toxicity. Um dose reductions. Air primarily done for a mile. Suppression, Um, and there you can decrease from five days to four days, four days to three days as your second dose reduction, and from three from days, one through 32 days 13 and five as your third dose reduction every 28 days. Um, for renal adjustments, there is no modification needed for mild to meet moderate. It has not been studied in severe renal impairment. Andi, for high Paddick adjustment, not necessarily in mild to moderate, has not been studied in severe impairment. Um, no significant drug drug interactions aside from drugs that are metabolized by the C. D. A enzyme, and these would again be other side of Dean analog, such as Jim Side of being or say, Terra Bean adverse effects. Most commonly occurred were fatigue, constipation, hemorrhage. My al Jas and Yukos itis are thrilled. Jas. Nausea, dyspepsia, diarrhea, rash Go back there. Thank you. Dizziness, oedema, headache, respiratory tract infections and federal neutropenia, and the most common grade 3 to 4 lab abnormalities were decreasing. Neutrophils, platelets and hemoglobin again for monitoring and warnings. Um, mild suppression being the primary um, issue for monitoring so again recommended to do a CBC with differential prior to initiation in each cycle on important to delay subsequent cycles and dose reduced as recommended on and again important to consider embryo fetal toxicity. With this drug, the next medication that was FDA approved was Take Artois, which was approved in June 2020. A new car T cell product. This is FDA approved in adults with relapse refractory mantle cell lymphoma. Ah, this is a CD 19 directed genetically modified autologous T cell immune therapy. Um dozing administration. Important to pre treat with a limp oh depleting chemotherapy regimen. Recommended regimen is cyclophosphamide. 500 mg per meter square in combination with flu. Doreen, 30 mg per meter square, Damon. Day minus five day minus foreign day minus three. Um, pre medicate with acetaminophen, um, and H one and I histamine such as diphenhydramine. 30 to 60 minutes prior, um, doses two times, 10 to the six car positive, viable T cells per kilo of body weight. Um, that does will be max dosed for patients above 100 kg. Um, and the approximate volume that that's delivered to the patient is 68 MLS of suspension tubing is primed with an S. The product is actually thought prior to administration to the patient in a warm water bath at about 37 degrees Celsius on bits administered within 30 minutes of thawing by gravity. It's also important that the product to be agit, gently agitated during thawing and infusion to prevent cell club clumping so that all of the product gets into the patient in terms of adverse effects. So this does. This product does have an F D, a black box warning for cited kind release syndrome as well as for neurologic toxicity. Um, it's all only available through the Jakarta's Room's restricted program on. That's because of the life threatening reactions that Kara's route result of the set, a kind release syndrome and the the neurologic toxicities eso. The serious events related to cite a kind of release syndrome are hypertension not responsive to fluids or hypoxia requiring supplemental 02 tachycardia as well as kidney injury. Um, so monitoring and providing supportive care, such as total is a map and are steroids occur per the second release syndrome and neurologic grading system. The car talks grading insists system Most common other than the Sierras earner. Neurologic adverse effects would be prolonged side of penas and severe infections. So in terms of warnings on um and monitoring for the prolonged side opinions, we would monitor the CBC for several weeks. Post infusion on Bring the patient for transfusion is needed. Um, Typo Gamma globulin AMIA can persist for months after treatment, so it's important again to monitor and provide replacement as needed. Um, and patients should also be counseled that they shouldn't be driving or using heavy machinery for at least eight weeks after treatment. The next FDA approved medication is Tafa Cinema, but which was approved in July of 2020. Um, this was approved in combination with Lana, Lana mind and adults with relapse refractory diffuse large B cell lymphoma, including diffuse large B cell lymphoma arising from low grade lymphomas. Who again are not eligible for autologous stem cell transplant? This is a seating 19 directed antibody. Dozing again is 12 mg per kilo cycle. One would be day one for 8, 15 and 22 of a 28 day cycle. Cycle two and three are 18 15 and 22 of the 28 day cycle. And then from cycle for onwards, you would be infusing it Day one and 15 of the 28 day cycle on all of these infusions, Um, do again require an escalation tight rations rate. Um, it is recommended to pre medicate these patients again. Tylenol, Benadryl on H two and H histamine such as for motive be promoted dean, and you're glue glucocorticoids drug drug interactions. There are none that are clinically significant. Most common adverse events. We've got subpoenas, fatigue, diarrhea, peripheral oedema, respiratory tract infections as well as decreased appetite. Um, for monitoring, infusion reactions. Um, really only occurred in about 6% of patients and 80% of those a carton either cycled one or two. Um, and really we're managed with temporary interruption of the infusion and supportive care. Um, if patients dio have a great for adverse reaction related to infusion is recommended to permanently discontinued treatment for Milo suppression, there is quite a bit of Milo suppression. Grade three and four neutropenia occurred in about 25% of patients and grade three and four throw Massetti Dapena occurred in about 12% of patients. Um, there are dose reductions that are dependent upon platelet count Azaz. Well, Azzam new triple count neutral account with fever on bond, extended frequency of of A and C less than 1000. Um, the important thing is that you would withhold resume the Tafa City mob, but you wouldn't necessarily decrease the dose. It is recommended to instead decrease the dose of the level of the mind component. Um, they're all also was a An increase in the amount of infections that occurred about 7% on these were primarily bacterial, fungal and viral on get important Thio, consider the embryo fetal toxicity. The next FDA approved product we have is blend rep that are Blanton map, which was approved in August of 2020. Um, this again was FDA approved for patients with relapsing refractory multiple myeloma who have received at least four prior therapies. Um, these again should include an anti CD 38 monoclonal antibody. Prodi is, um, um inhibitor and an immuno modulator. Torrey Agent again, The mechanism of action is that this is a B cell maturation and managing directed antibody, uh, conjugated with a micro tubules inhibitor, which is m m a f dozing administration. We've got 2.5 mg per kilo, which is given every 21 days. Dose reduction would include decreasing at 1.9 mg per kilo. Um, there is no renal or hepatic adjustment, uh, necessary. Um, and these patients are recommend are given the infusion over 30 minutes. Um, it is recommended that these patients be given a lubricant. I drop eso preservative free, which they would administer to themselves four times a day, beginning with the first infusion, um, drug drug interactions. Um, the hydrolyzed M M a. F component is a substrate of various transporter systems. So if there are other drugs which use similar transport systems, they may interfere with elimination of this product. Um, in terms of adverse effects, um, this again has an F d, a black box warning related toe ocular toxicity, and it is only available through the blend Rep Room's restricted program on. And that's because this agent can cause changes in the corneal epithelium, which can range from dry eyes and blurred vision to severe vision loss. We can't, which can be irreversible, so I'll they'll make. Exams are required at baseline prior to each dose and promptly for worsening symptoms. Um, it is important to modify doses according to the corneal adverse reactions for the V. A scale on what the V A scale is basically, um, a a corneal examination finding combined with visual acuity, uh, in terms of monitoring and precautions throughout beside a penny a card in 69% of patients. Eso again you would consider withholding or dose reducing based on on severity. Infusion related reactions occurred in about 18% of patients. Onda Geun There are concerns for embryo fetal toxicity, and the last product we have is a decided dean tablets approved in September of 2020 this again it was is indicated in adults with acute myeloid leukemia who achieved first complete remission or complete remission within complete blood count recovery following intensive induction chemotherapy who are not able to complete intensive curative therapy, such as, um intensive consolidation or eliminating a login eight stem cell transplant Again, The mechanism is that induced DNA and RNA metal transfer races does the administration. It can be taken with or without food. Um, it is recommended to pre medicate with an anti matter because this is considered minimally and meta genic 30 minutes prior to each dose for the first two cycles, it can be omitted thereafter if there are no reports of nausea. Vomiting, um, the doses 30 mg. I'm sorry. Excuse me. 300 mg early given daily days one through 14 on a 28 day cycle until disease progression, um, dose reductions for adverse effects. Um, our stepwise and fashion so you can decrease to 200 mg daily, one through 14 or a Z, your first dose reduction and then 200 mg daily days one through seven as your second dose reduction. Um, there is no requirement for adjustment due to renal impairment. It was not studied in patients in moderate to severe hepatic impairment. Drug drug interactions co administration with the members, all did increase the is excited in Orel a. C by 19% adverse effects again, Most common nausea, vomiting, diarrhea. Onda Gennett is considered low. A medic risk load. A minimal medic risk, but it really is very patient dependent. Uh, fatigue, Yesenia, constipation, pneumonia, abdominal pain, Earth, Algeria, decreased appetite, febrile neutropenia, dizziness and pain in the extremities. In terms of monitoring, it's very important that you do not substitute any ivy or subcutaneous is exciting formulations for Orel and or vice versa. There are substantial differences in pharma co kinetic parameters. Onda, dosed and schedule of both of these are different, so do not enter change. These Milo suppression again recommended to do CBC with differential every other week for the first two cycles and then prior to the start of each cycle thereafter, if there's any requirement for dose reduction again recommended to go back to every other week, CBC monitoring, um, for two cycles, and then you can go back thio prior to the start part of each cycle and again, important toe withhold treatment and dose produces recommended. So with that, any questions that we can answer for you. Thank you, Jane. Thank you, Rina. That was a lot of information that have to go over in such a short amount of time. Very informative. I know it's technically the start of the morning break, but we do have some questions that we want to get to an answer. Eso the first one and I will apologize. I've always been terrible pronouncing these medications, so hopefully you'll be able to figure out decipher which ones I'm talking about. The first question is for you, Jane. What is the status for Hambro Liz? A mob with Carville Platinum Taxol as neo adjuvant therapy for non metastatic breast cancer, followed by Dr Robison Cyclophosphamide. Um, with with for non small cell lung cancer, Is that what they were for non metastatic breast cancer, non metastatic breast cancer? Unfortunately, I would just recommend that they go to the National Conference and Cancer Network on kind of review. Those guidelines for breast cancer. Um, I don't want to speak to something I'm not, uh sure about Thank you on the next one Would could go to both of you. So, with HIV therapies, authorization for treatment has taken care of behind the scenes with oral therapies and this person's clinic patients and families have to be actively involved in communication with specialty pharmacies. Sometimes patients fell to let their office No, when they received the prescription and they can get lost to follow up. Do you either of you have any tips to help improve the process? Yeah, that's a very good question. Um, because, you know, cancer therapies going towards Orel agents. A lot of these are specific toe Onley, certain specialty pharmacies, Thio, and majority of the time they're so expensive that they require prior authorization paperwork. Um, you know, patient assistance programs and things like that I will speak Thio. You know, our clinic. We have a really good group of people that get involved with our outpatient pharmacies and helping us with prior authorizations and paperwork in order to help kind of facilitate that communication with our patients. But in general, when I'm consenting impatient, I tell them that this is going to take time to get It's not gonna be an immediate medication that they're gonna be able to get filled. It requires us to fill out paperwork. Um, that is, um can take a week or so Thio get cleared even for unapproved indication. And then majority of the time it's gonna have to be sent to a mail order pharmacy in which they're going to get a phone call from a 1 800 number. And to be sure and answer that phone call in order Thio, facilitate the insurance and delivery confirmation that they need, I think setting expectations for the patients and then telling them Let us know when you get the medicine s O that we know what day you started to ensure our follow up his appropriate, or if you need more, more information about the medication. If you've forgotten what we've gone over by the time that you get the medication, just be sure and reach out to us. And that's usually my approach. When I'm counseling, a patient is to just set their expectations up so that they know what to expect for for these medicines, and it tends to work out better that way. Really? Yeah, I would agree with chain um in terms of our process, we also have a great team from a prior authorization standpoint that contact the patient with paperwork, financial information. We're also going thio We have started a script specialty pharmacy tohave just a little bit more control over the specialty pharmacy medication process. Um, again, as Jane mentioned, there are products that can't, you know, have can only go through certain specialties. Um, in those cases were in pretty close contact with those specialty pharmacies to know when those patients are, you know, expected to get medications deliver and then in contact with the patient as well. Um, going back and forth with these medications. Andi, I would say, from an education process, that's absolutely true, you know, giving the patient lots of expectations of timeliness. Onda also, you know, empowering them to contact us when they do receive medication on. Now that we have, you know, ways Thio, you know, message clinic nurses, and so on and so forth through, you know, RMR, that actually has really streamlined some of the process. Um, the other components that we're looking at is really kind of looking at a real service around Orel specialty medications, which would include the compliance and the counseling as well as the dispensing. So kind of just bring it under one umbrella. So we're working on that as well. Perfect. Thank you both. Next question, Reed, I think this one would be for you with dare to mob hire a lot of days. Do you need to give the patient a dose of ivy? Dar selects first. You do not. Actually it is FDA approved to start de Novo. I will say that there is a higher potential for some of these quote unquote later react administration reaction, but can occur. So something that we've been kind of going back and forth about, um is that given that the median times onset of those reactions can be up to 33 to 4 hours, how long do we keep a patient for monitoring after administration? But no, you do not have to start a patient on Ivy in order to use the subcutaneous. You can use that in patients that have never been treated before. Perfect. Thank you. We had an attendee asked, Can you please review the Herceptin and project a injection again? Um, review that again? Um uh, the sub Q formulation. I don't have my slides up, but basically it's the sub Q formulation of both of the drugs and combinations. So they're indications right now are for breast cancer. Her two positive disease. I've paid particular attention to what the dozing is because there are specifics around that regarding which indication you're using. Um, but it starts with an initial dose on a zai mentioned before subcutaneous lee over eight minutes and then maintenance doses given over five minutes, uh, to be given in the thigh on by health care providers. Um, so the patient can't do this on their own at home. And it did have some observation guidelines recommended with how long to monitor the patient after which specific dose they received. Perfect. Thank you. Way. Had an attendee also asked, can you discuss immunotherapy as a breast cancer treatment? Yeah. I mean again, I would just refer to the National Conference of Guidelines or any kind of breast cancer guidelines. Really? To get over specifics and individual tumors. Okay, Perfect. Thank you so much. Those were all the questions submitted. Eso thank you again to both of you for your informative presentations. I do want to remind the attendees that you do have access to the slides of the presentation on the livestream event page. You can click on the title page on the page and download from there. Eso just a reminder to everybody because I think some questions pop up during our presenters. When there showing their slides. Everybody's interested in how to get those. So thank you both again. I will release the attendees for their morning break and we will resume at 10. 30 Pacific Standard time with our next speaker and presentation. Thank you.
