 the supportive therapy for our myeloma patients, is this working? There we go, thank you. Alright, so we know that myeloma is a highly treatable disease, but at this point in time is considered incurable. Hopefully that will change in our lifetime, right? And so the overall serates have significantly improved due to the recent advancements and newly approved novel agents, but with its survival improvements can lead to more comorbidities for our patients. So the goal of treatment is to control the disease to prolong overall survival, but we also need to preserve quality of life. So understanding what these side effects could be and prompt management of these side effects can really improve quality life for our patients. So we know that the effects of myeloma itself can affect the bone marrow, can cause myelosuppression, those plasma cells are overcrowding the bone marrow, it can cause renal dysfunction, you know those free light chains, those monoclonal antibodies can be really toxic to the kidneys and also bone damage. So for our bones we know that about 85% of our patients have bone disease and this is really because these myeloma proteins can up-regulate the activity of osteoclasts and kind of suppress osteoblast maturation, you know those two systems working together to maintain the bone health. And we can see weakened bone holes in the bones from this exact mechanism of action. So the widespread bone destruction can lead to hypercalcemia, it can cause fractures because the bones are really brittle, we can see sometimes spinal cord compression, we can see these kind of lytic lesions and sometimes we can see really weakened bones such as osteoporosis and osteopenia. So the main state of treatment for bone disease is actually using bisphosphonates for myeloma and how they work is they inhibit the osteoclast activity and cause osteoclast apoptosis. So it slows down bone destruction, it doesn't really build bone it just kind of works on those osteoclasts and it can decrease pain and can also reduce skeletal related events meaning reduce risks of fractures that can happen with myeloma. And there's also an anti-myeloma benefit to these drugs that we don't entirely understand because there was a study that was published in 2013 that looked at the usage of bisphosphonates particularly zometa for patients who had myeloma and the patients who were on zometa versus not on zometa actually live longer. So there is a survival advantage and an anti-myeloma effect to these drugs. So we typically give these the two drugs that are approved from myeloma zoologonic acid and pomegranate are given as IV infusions once a month for usually the first year and then we'll spread it out thereafter to maybe every three months and there are pretty rare side effects but important to note they can affect kidney function so it's important to know what your patients create and every time you dose these drugs. There's a risk of fractures of the long bones of the femur and it can be usually bilaterally and it can be it can happen with little to no trauma to the area so it's really important if your patients reporting groin pain or thigh pain to investigate to see if they have this fracture if they've been on bisphosphonates for a long period of time. It can cause flu-like symptoms maybe within the first three days of getting the drug typically with your first dose and not really with subsequent dosing happens in about 10 to 20 percent of patients manifesting as kind of a low-grade fever or chills or body aches can be mitigated with taking something like Tylenol and then we do see this very rare side effect called osteonecrosis of the jar ONJ and so the risk is increased with more exposure to these drugs and also having a recent invasive dental procedure so we always tell our patients that if they have to have any sort of major dental work to make sure they get that done before they start bisphosphonate therapy and make sure their dentists know that they're on bisphosphonates because when they are dentists tend to be a little bit more conservative with the type of treatments that they do because the risk increase if there's exposed bone in the jaw so maybe tooth extractions or even implants can increase the risk. There was a study that showed that patients who were on Zometa for more than two years and had a dental procedure they had about a 2% risk of developing ONJ so it's rare but it is something that's important to note. How else we manage bone disease? Well you know treat the underlying problem the myeloma but we can also do surgical procedures like vertebroplasty or kyphoplasty and they're minimally invasive so vertebroplasty they're basically kind of reinforcing the collapsed vertebrae and then kyphoplasty is they're inserting a balloon inflating it in the collapsed vertebrae and filling it with a bone like cement and this is minimally invasive patients can get pretty quick relief with this pain relief maybe within the first month of getting the procedure and it really isn't a hospitalization of all with this so it's a nice option for our patients who have really painful compression fractures. We can do radiotherapy it's really only for a select patient population because we know that radiotherapy can affect bone marrow function but if patients have painful plasma cytomas that could benefit from this will sometimes offer this and also if we see on imaging that patients have maybe an impending fracture we'll send them to our orthopedic colleagues to see if they need reinforcement. So the kidneys we always hammer to our patients that they really have to protect their kidneys not allow themselves to become dehydrated and that's because there's several factors at play so the myeloma can cause cast nephropathy the hypercalcemia we talked about can affect your renal function hyperviscocity and light chain deposition disease and amyloidosis can all call cause renal dysfunction and so other causes to such as other comorbidities such as hypertension or diabetes can affect your kidney function dehydration and certain medications so the nonsteroidal anti-inflammatory drugs we always tell our patients to stay away from make sure they're not getting IV contrast and there's certain drugs that we give them that can affect their renal function too such as the bisphosphonates and also some drugs we know we have to might we might have to dose reduced due to impaired renal function such as some of the immunomodulatory agents like Len Linamide. So how do we treat this? We make sure our patients are well hydrated I always tell my patients that they should be coming into clinic with a bottle of water because they should not allow themselves to get dehydrated make sure you correct that hypercalcemia because that can really influence the renal function and teach your patients not to take nonsteroidal anti-inflammatory drugs and make sure they understand what the brand names are and the generic names are because they might not know what they're taking is a nonsteroidal anti-inflammatory drug and if they ever see another physicians who's ordering a CAT scan make sure they tell the physician that it should be without contrast sometimes plasma freezes can help if they have really a lot of monoclonal antibody burden so you're just kind of getting rid of the excess monoclonal antibodies but doing plasma freezes but really treating the underlying myeloma as the way to go and then also dialysis if kidney function is really impaired. So here is a list of the approved agents for the treatment in months of myeloma it's not an exhaustive list because I don't have the alkylating drugs that we use such as bendomostine and cyclophosphamide and mouthland and the good old steroids that patients can never get away from but we have our immunomodulatory agents we have our proteasome inhibitors we have our monoclonal antibodies and we have our HDAC inhibitor. So you can see that these drugs they're break down by class and drug itself they can cause a slew of side effects for our patients so cytopenias increase risk for infection some gi distress we can even see issues with you know their blood sugars from the dexamethasone or prednisone we're giving our patients we can see even some cardiopulmonary effects so it's really important to understand all the risks of using these drugs and help prevent some of these side effects that can occur. So peripheral neuropathy we know that this can happen either from the disease itself or some of the drugs that we give our patients and it can range from sensory defects to actual neuropathic pain you know patients can just notice some intermittent numbness to constant numbness that can manifest to kind of electric shooting pain or pinpricks or a burning sensation that they have in their hands or feet and so it can happen like i said from disease or treatment itself amyloid deposition can do it hyper viscosity can do it and we know that the incidence of high-grade peripheral neuropathy can be mitigated with certain changes in some of the drugs that you use so bortesimib we know the risk is decreased if you give bortesimib once a week versus twice a week and we know it's also decreased if you give it subcutaneously I can tell you here at Hackensack we pretty much never give bortesimib intravenously and we really only give it as a sub-q injection because the efficacy is the same but it's much more better tolerated thalidomide we know that this is dose dependent meaning kind of the longer you're on it the more likely you're able to develop neuropathy and it's less it's a little bit harder to reverse neuropathy associated with thalidomide with bortesimib we know about one-third of patients can have irreversible peripheral neuropathy so we can help two-thirds of patients if we recognize it early and give them a break so how do we manage it if we know it's related to the drug we might have to modify the dose or the schedule of the drug meaning if it's from bortesimib we might want to change from going twice a week to once a week or you may need to give the patient a break to see if the neuropathy gets much better we can also try oral medications such as deloxatine or progabalin gabapentin some of the tricyclic antidepressants can be really helpful like nortriptyline or amitriptyline and even opiates can sometimes be helpful but those neuropathic medications seem to be a little bit more beneficial there's compounded creams that you can use we don't use them very often some patients find them to be a little bit more painful than anything else it usually has a mixture of stuff in there like a muscle relaxant or a high dose opiate like ketamine and then just teaching your patients about really how to protect themselves so make sure they don't have clutter in the house if they have trouble walking so they're not tripping over anything make sure they're using safety features maybe installing stuff in their bathroom make sure they're using canes and walkers as needed and if they're having a lot of trouble with their balance maybe physical therapy can be beneficial and even calling our neurology colleagues because we know they can do sometimes some EEG testing to figure out the origin of the neuropathy and see if they have any other better ideas than we do. So clots is a huge issue for cancer patients we know that cancer patients are inherently hypercoagulable myeloma is no different and we can see our patients can get either DVTs or PEs sometimes just from the drugs that we're giving them or just inherently at risk so we know that these clots can result from kind of an unregulated activation of both the coagulation that occurs with endothelial damage or reduced blood flow and just inherent hypercoagulability it's important to recognize the signs and symptoms of a clot it can be very insidious sometimes patients can have very minimal swelling in their legs not pain not heaviness not redness and you send them for you know adopter study and they can have bilateral DVTs so how do we prevent clots we have to understand what our patients risk factors are so obesity a previous history of a clot can tell us that they're already inherently hypercoagulable having a central venous catheter certain comorbidities and even certain medications like the erythropoiesis stimulating agents that we give can increase your risk of developing clots we have certain myeloma related risk factors too such as hyperviscosity or even certain drugs that we use and it's important to recognize the risk factor where they lie on the scale because doing something like aspirin can be sufficient but if they have more risk factors doing therapeutic anticoagulation is the best way to go so the best way to manage it is to recognize the risk and prevent it i can tell you we pretty much use a low dose aspirin for our patients who are low risk but if our patients are at high risk we'll use therapeutic anticoagulation and we tend to ad-hack and sac to lean a little bit more to the oral agents a little bit easier for our patients to avoid taking another shot every day and also watching how much corticosteroids we use because there was a trial that showed reducing the dose of dexamethasone there was a trial showing high dose dex with rev or low dose dex with rev and the patients who had a lower dose of dexamethasone with revlimid had less clots and actually less infections we can do Doppler studies or a vq scan and also if patients develop a clot while they're on therapy switch them over to therapeutic anticoagulation so myelosuppression we know is a problem for our patients because the plasma cells are overcrowding the bone marrow and causing these low blood counts and the drugs that we give them itself can be myelosuppressive so it's important to recognize the risk and when patients naters are going to be and anticipate that and make sure they understand what the signs and symptoms of myelosuppression can be so check those blood counts frequently particularly during that nadir period if your patient has poor bone marrow reserve maybe you need to check it more frequently while they're on therapy make sure they're not on any other medications that can lower their blood counts besides their myeloma therapy if they're really symptomatic from their anemia maybe giving them a transfusion to improve their oxygen carrying capacity can be helpful trying those erythropoiesa stimulating agents may be useful too you can try prokrid or aeronasp and maybe look for other underlying issues that can cause anemia such as deficiency in iron or B12 or folate we've had a couple of patients develop this kind of coombs negative hemolytic anemia on some of the treatments that we're giving them so make sure you look for that and correct it if you're seeing a lot of surrogate markers such as hyperbilarubinemia or the anemia is becoming more pronounced and long-term usage of some of the drugs like the immunomodulator drugs can cause hypothyroidism which can in turn cause anemia so make sure you're checking for that too so for our neutropenic patients we can offer them growth factor support more importantly teach them about infection precautions you know i had a patient yesterday who was very neutropenic and was very sad that i told him he couldn't have a huge birthday party this weekend because he could develop a life-threatening infection with all his grandchildren were playing to be at the party so it's really important to explain to your patients that it's they really need to avoid large crowds wash their hands really well it's so easy for someone to cough sneeze into their hand touch a surface your patient touches that surface rubs their eyes rubs their nose make sure they have a thermometer at home it's so easy to ask your patients if they're experiencing fevers they'll tell you no but your second question should be do you have a thermometer at home because sometimes the answer will be no so how do you know you have a fever if you don't have a thermometer at home and so make sure patients know that if they do have a fever it's a medical emergency so for febrile neutropenics we have to basically panculture these people give them empiric IV antibiotics Tylenol to bring the fever down and also for thrombocytopenia make sure for patients are really at high risk for spontaneous bleeds with a low platelet count give them a platelet transfusion and also make sure we're holding anti coagulation if their platelet count really low so infection we know our patients are really at risk so the immune deficiency of myeloma patients is caused by many things so the myelosuppression they have suppression of their normal immunoglobulin because of that excessive monoclonal antibody that they're producing they have deficiency in their normal antibody response because that monoclonal antibody that they're producing it's kind of non-functional not helpful for their immune system there can be a shift in their microbial flora so they're really at high risk for developing bacterial and viral infections myeloma patients have an inherent problem with their humeral immunity so they're at high risk for encapsulated bacteria infections such as homophilus infections and streptococcus so they're also at risk for zoster and that's from the myeloma itself the treatment they get we give them such as proteasome inhibitors daratumab and even stem cell transplant so it's important to recognize this and prevent it make sure they're on antiviral prophylaxis if they develop zoster recognize it quickly and treat it so because the risk is always developing post-herpetic neuralgia which is really terrible for our patients and we do not recommend the shingles vaccine for our patients it's a live vaccine and our patients should not be getting it but we can also make sure that we are finding a source of infection if we do suspect one so sometimes we'll do a respiratory pathogen panel to check for the most common viruses a lot of my colleagues joke in the office that i order this way too much but you know when you have a patient who develops the flu in the middle of the summer and has a develops a flu in april i had a patient who developed the flu twice this year um in the summertime and just in the non flu season so it's important to see that these people can be at risk for these kind of opportunistic infections when the general population is fine chest x-ray looking for pneumonia they're really at risk for that empiric antibiotics if you think they do have an infection vaccines are important so getting their seasonal flu vaccine and their pneumonia vaccines very very important they may may not be able to mount the response to these vaccines at a patient who doesn't have myeloma but there's still a protective benefit there and if your patients have really they have chronic infections chronic sinus infections respiratory infections and really low levels of igg you may want to offer them intravenous igg to see if it can help them if your patients are having a lot of trouble with diarrhea may want to do a stool culture to see if they have C. diff or an o.m.p. urinalysis and urine culture if they're having urinary symptoms blood cultures antifungals growth factors but i just want to remind you that sometimes patients may not really mount the same kind of immune response to an infection because the corticosteroids can really mask the typical signs and symptoms of an infection so you really have to be careful and look for insidious things and make sure your patient is not infected so fatigue so this is one of the most serious complications of myeloma because it really really reduces quality of life and it usually starts with diagnosis and just gets worse over time and it's not the type of fatigue that you and i know after working a long day at work it's more the type of fatigue that's really not relieved with rest you know you and i may be able to take a nap and then get going and feel refreshed a lot of the times our patients don't feel that way and they're not really sure but they think it's due to increase inflammatory cytokines so it's important to kind of recognize what the risk factors are so you know anemia nutritional deficiencies if they're not sleeping well from the steroids we keep hammering into them even depression a lot of the time patients say they don't feel depressed but it's really manifesting as difficulty sleeping and having little interest in no energy and things that they love to do pain medication can do it just being sedentary can do it it's just like with babies right sleep but get sleep so the more you sit the more tired you're going to be and even some hormonal changes can do it too in the myeloma treatment so we have to tackle it from various standpoints correct anemia if we think that's the cause if it's drugs doing it maybe they just need a little bit of a break you know these patients are going to be on treatment probably indefinitely so maybe they just need a little bit of break just to kind of refill their tank um sleep disruption disruption can be a big problem so educate your patients on proper sleep hygiene make sure they're not drinking a ton of caffeinated beverages before they go to bed and try and tell them you know if you are trouble having trouble sleeping please don't turn on the lights and start vacuuming your house because your body's going to get confused and think it's time to stay awake and and be productive for the day so just try and rest and close your eyes if it's because their mind's racing a lot at night maybe giving them a benzodiazepine but maybe a sleep aid is really where they need to go such as ambien or even lunesta sometimes our patients don't have energy because they're just not eating well so it's really important to lean on our nutrition colleagues our nutritionist is fantastic she can really come up with an individualized treatment plan for our patients and sometimes patients are dehydrated they just see an IV hydration to help them get going depression is a huge problem can cause fatigue we have a monthly support group here for our patients or myeloma patients it meets the third Thursday of every month we also have social workers that can help our patients sometimes they need more advanced help such as seeing a psychiatrist or even having psychotherapy and the demands of cancer care itself are very fatiguing you know a lot of our regimens that we give patients make them come twice a week sometimes two days in a row three weeks on and one week break so we're coming to the clinic sometimes six times a month maybe more than that if you have to check them more frequently because you're worried about their counts so patients can be just really exhausted with the cancer care itself so i always tell my patients make sure you're leaning on your caregivers to help you with other things that you don't need to do run into the grocery store run to the laundry mat let them do those things so you can conserve your energy to do more important things such as that holiday dinner or their birthday that you really wanted to have and make sure they're exercising so basically exercise is the only thing that's been proven to help with cancer related fatigue and a lot of patients just say you know i don't have enough energy to exercise but once you get those natural endorphins pumping they actually do feel better proper pain management as well and of course check for hormonal imbalances so gi distress we see a lot of this with our patients most of the time not related to the myeloma itself but more the treatment that we give them and there's tons of risk factors here so for nausea the hypercalcemia being constipated being anxious we know our female even our younger female patients are really at risk for nausea pain medicine can do it constipation there's lots of risk factors there too such as uncontrolled diabetes we forget about that sometimes just not eating well can cause constipation and diarrhea you know recent exposure to antibiotics can do it and sometimes people have pre-existing issues like lactose intolerance or irritable bowel syndrome so how do we manage nausea so if it's due to drug we'll try and modify the dose but we really lean on our supportive medications for this so and sometimes it requires drugs from all of these classes so our five ht3 receptor antagonists our neuro one receptor our neuro kind in one receptor antagonists our dopamine receptor antagonists and sometimes even using the cannabinoids can be helpful for our patients using marinol particular for patient has trouble sleeping and they have a low appetite and trouble with nausea sometimes marinol can be really helpful maybe the benzodiazepines are a way to go to to add on top of this alternative therapies like acupuncture bands or acupressure can be really helpful and teaching your patient about small frequent meals a lot of the times patients say you know I had my large pasta dinner and I felt really nauseous well maybe you shouldn't have your large pasta dinner how about small frequent meals just to get that nutrition in and make sure you tolerate it well and a lot of our patients have trouble with reflux in fact one of my patients just stopped me in the hall and said Amy I just want you to know I've been having reflux all day today so I said well what are you eating she was drinking you know coca-cola and eating a chocolate cookie so we talked a little bit about sometimes food can exacerbate it such as caffeine and chocolate but you know a lot of the steroids we give our patients can really cause a lot of gastritis so making sure they might need to be on a ppi or even on the h2 and even she said she's been chewing tums all day so talked about how to best manage that constipation we forget that almost all of our patients are on opiates and so they can cause a lot of constipation make sure their diet is appropriate relaster can be helpful for opiate induced constipation make sure they're not taking their 5HT3s very often and diarrhea make sure your dose reducing are delaying if you think it's related to drug make sure patients are slow down slow down slow slow down on laxatives make sure they're hydrating well they can use supportive medications like ammonium or lomodal even cholecystiramine can be helpful make sure it's not related to gvhd because sometimes I can really cause excessive diarrhea make sure they're eating appropriately and treat infections if you think that's the cause so now we have infusion related reactions as a problem for a myeloma patients we're lucky to have this usually our lymphoma colleagues had to deal with this now we do too so we don't really understand what the mechanism is but we think it's some sort of cytokine release and if usually occurs it's usually really quickly and usually with the first infusion and the symptoms can range so I always tell my patients if they feel strange in any way during the infusion let your nurse know so how do we manage it the best ways to prevent it so make sure your patients adequately pre-medicated start low and slow and there's some parameters for certain monoclonal antibodies so there's a risk of having a delayed reaction with deratumab up to 48 hours after getting the drug so patients need to take prednisone for two days after ilotuzumab they need to take it before they come and see you and how we manage it stop the infusion of course give them more supportive medications if you're worried about airway obstruction make sure you have epinephrine and make sure they're getting fluids we do see some skin reactions from time to time make sure they're taking antihistamines topical corticosteroids we can see injection site reactions with portesimib it's important to use the air sandwich technique to help reduce this make sure you're rotating the site of injection to help minimize this dyspnea can happen sometimes from drugs or underlying issues we have a ton of risk factors that can cause this make sure you're asking your patient if they're smoking and make sure they're not smoking they can sneak by us with that a lot of the time and so we manage this by basically correcting issues that can cause it so if it's heart failure doing it make sure we're getting a repeat echocardiogram if we think it's a clot do a vq scan and sometimes patients need supplemental medications to get them through so just in summary we basically have a lot of survival improvements with our new novel agents but it can also lead to comorbidity so it's and the adverse effects that can happen can happen really to pre-existing risk factors the disease state and the treatment regimen that we're giving them and a lot of this can really be potentiated by understanding what the risk factors are because we know a lot of these adverse effects can be managed more properly if we prevent it and harder to control once they happen and we know that if we can control this well and recognize it well we can improve our patient's quality of life that's it thank you i tried to wrap it up thanks sweetie so she only has like three minutes because she has to go speak next door who's got pressing questions for amy please you said with the hypercalcemia i was wondering if you probably don't recommend vitamin D actually vitamin D is really important but um the hypercalcemia usually is from the underlying myeloma itself not not mostly because a patient has taken a lot of calcium or tons although that does happen it's really from the underlying myeloma itself so treating the myeloma and also um supporting them with like calcitonin or bisphosphonates and fluids to correct the hypercalcemia but it's really important for patients to stay on vitamin D particularly living in the northeast we're all very vitamin D deficient here no i don't think it's going to make the matters worse but of course watch for patients calcium levels so that one of the issues with vitamin D and calcium supplementation because especially because you're dealing with an older population particularly the women they're on calcium and vitamin D because that's what their doctors tell them to take all the time we those are actually very important to make the bisphosphonates work better but we don't usually recommend them to their myelomas under control so they need to take a holiday from their vitamin D calcium until we get their disease under control and then they actually can go back on it because it does make you know it makes the the bisphosphonates work better so they need to take a holiday make sure they're not hypercalcemic because they're taking exogenous calcium control their disease put them back on it because it helps their bones other questions yes we can use exjiva we can all use exjiva in refractory hypercalcemia it is approved for that so if they want to bisphosphonate they become hypercalcemic you can give them exjiva do you have any that do you have any idea when the news may have no i know i've been waiting the trial has been done in myeloma they didn't approve it no if you look at the original exjiva trial there was only there was a handful there was like 200 or something like that out of the 1800 patients and they didn't feel the FDA didn't think that was a large enough subpopulation to approve it so a couple years later the company finally decided to do an exjiva versus zoonodronic acid study it's been done the results are not available so we can't answer that question