What is linvoseltamab (LYNOZYFIC)?

What is linvoseltamab or LYNOZYFIC and how does it work?

Linvoseltamab is a bispecific antibody. We all know about antibody, helps us protects against infection. The antibodies are very specific what is bispecific. bi means two. Specific, it is specific for two different targets.

One it binds to the cancer cell to the myeloma cells. And that is the BCMA as a target. And then the other one is to bind to the patient's own immune cell the T cell the CD3. So that is expressed on the T cells.

Previously, the T cells, when they came across the myeloma cells, the myeloma cells used to masquerade and say, hey, I'm your neighbor. You knew me. I've been here all along. But now when you have the antibody, the T cells are told this is no longer a good cell. This is an enemy. Then the T-cell is brought very in close proximity to the cancer cell. Then the T-cell is able to kill the cancer cell. So this is the advantage of bispecific.

How is linvoseltamab administered and what is its dosed?

Linvoseltamab, currently is administered intravenously, not subcutaneously, As a class for all the bispecific antibodies, you know there is step up dosing. That means we give very low dose then little higher dose. And then finally full dose.

So in linvoseltamab, first dose was only five milligram. The actual dose is 200 milligram full dose. So giving five milligram that is 1/20 of a dose on day one of week one. and you observed them in the hospital just for 24 hours. And then double Then the next week, day eight, they get 25 milligram. So 25 milligram out of 200 it's one eighth of the dose. Again, you can observe them in the hospital for 24 hours and release them. And then finally you get the full dose. It is not necessary to hospitalize a patient.

As I said a little bit earlier, bispecific antibody binds to the cancer cells and to the T cells and brings them in close proximity. And the T cells then, you know, secrete cytokines to kill the cancer cells. linvoseltamab, they recruit your own white cells to fight the cancer cells.

If you have a smaller amount of antibody given you look at fewer T cells and you kill smaller proportion of the cancer cells, so you reduce the amount of cancer that is there. the second time around you give a little higher dose. Again, you recruit more T-cells to fight more of the cancer cells. But because it is step up, this cytokine which are released by the T cells are measured. So the effect on the patient, the side effect is much less. And you can quickly abate it with the use of steroids and Tylenol and tocilizumab,

Once step up dosing is complete, what is the administration schedule for linvoseltamab?

So the patient goes through day one which is week one, then day eight which is the beginning of week two. Then day 15 they get the full dose. That is week three. Then they get ten weekly doses, okay. And then they start on the 14th week or at the end of three months. They start getting it every other week, okay, for the next three months. And at the end of six months, if the patient is already in very good partial remission, not a complete remission, then you can give it once a month. That's how the actual trial was designed, and many patients were able to go to monthly by the end of six months.

Can linvoseltamab be given in the community setting, after step up dosing?

And then after you have received, you know, first full dose and another full dose, you can now safely receive the treatment from a local oncologist closer to home, provided of course they are all REMS certified.

What premedications are used with linvoseltamab? Are premedications continued after step up dosing?

Premedication is always given whenever would be give any kind of antibody or immunotherapy to the patient. So initially our reason is to make sure there is no allergic reaction. But linvoseltamab is a fully human antibody. So reaction to is that way is minimal. But still we will give them Benadryl. It is for preventing any allergic reaction. We gave them some steroids which again to prevent any allergic reaction. And then we give Tylenol so that they don't have fever right away. And basically then you give them linvoseltamab. So that is a premedication. First time around.

But after you finish the step up dosing and the patient tolerates it very well. And there has not been any reaction. As I said, linvoseltamab is a fully human drug. You don't need to keep giving the premedication. So you give the full dose on day 15 and maybe another full dose just to be sure everything is okay. And then after the treatment you don't have to keep giving the premedication.

What are the main side effects of linvoseltamab?

We can break it into two broad categories. One is what is common for any bispecific therapy or T-cell, you know, redirection therapy. They all have one thing in common. That is whenever the T cells proliferate and try to kill the cancer cell, they release cytokines to kill the cancer cell. So you have a body reacts to the presence of cytokine okay. That is called cytokine release syndrome.

What are the symptoms of cytokine release syndrome? When is it most likely to occur? How severe can it be?

So cytokine release syndrome. As I said, when the T-cells are revved up to fight the cancer cell, it is almost like the white cell revved up to fight the bacteria. What do you develop? Fever. That's common. So that's the first symptom. And if you just have fever, then it is called cytokine release syndrome grade one.

Now if it is more like if you have pneumonia and you have to be hospitalized and your blood pressure is fluctuating, but you need I.V. fluids because your blood pressure was on the lower side, that would be grade two. So in cytokine release syndrome, if your blood pressure kind of goes down, but it goes back up with the IV fluids, then it is called grade two.

Now, if the blood pressure is so low and the patient looks ill and you actually have to give some medicine to hold up the blood pressure to the normal range so kidney doesn't get affected, then it will become grade three. Okay.

So it is a matter of looking at it and then grade four, the patient need a lot more support, oxygen support and things like that. So that will become grade four. Patient may even need to be in the ICU. Grade five if it's overwhelming if a patient dies, that is called grade five.

But the good news is in linvoseltamab, grade most of the CRS is only grade one. At the most grade two. 1% is grade three. No, grade four or grade five.

To learn more about the symptoms of CRS, how it is graded and managed. Be sure to watch the HealthTree University video on this topic in our CAR-T treatment course.

Besides CRS, what are the other major side effects of linvoseltamab?

when cytokine release syndrome. reaction is higher then it could also call neurological symptom. And that is what is called ICANS; immune effector cell associated neurological syndrome. That means this is immune effector cell which is here. It is the T-cell, related neurological symptom. When the T-cell proliferate and produce cytokines that are neurologic and that is called ICANS.

How often is immune effector cell associated neurological syndrome seen with linvoseltamab? What are the symptoms of ICANS? What is the most common grade seen?

Immune effector cell associated neurologic syndrome. basically the T-cells are multiplying killing the cancer. And during that time when that action is happening the cytokine can make the patient feel a little bit altered mentally.

So if you ask them to count, you know, 195, 90, 85, you know, normally we can count five. Don't make me count six below, you know, 90, you know, 194. Then I have to think 88. Even now I would have ICANS, but if you are able to count backwards. But the patient may find it difficult, you know that they are not able to count backwards, so they are slightly altered.

Sometime it could be more. Then you ask them common symptom. Who's the president, who's you know and name this or something like that. Recall, the recall memory. If you give them three names, you know, book pen and paper, can you recall what did I say in that same order, they may be able to say book and then the others may or may not. So that's a level two.

Sometimes, It could get even more, you know, in which case they are not really able to answer. They are confused and things like that. So there are also grading in, ICANS. But generally ICANS with bispecific antibody and linvoseltamab is uncommon.

So grade one 2%, grade two 2%, grade three 2%, no grade four. So it's very, very low. So it is not common.

To learn more about ICANS and how it is graded and managed, watch the Health Tree University video. What is ICANS in our CAR-T treatment course.

Are there any delayed neurotoxicity, such as parkinsonism associated with linvoseltamab?

Delayed neurotoxicity as opposed to ICANS; ICANS happens when the T cells are revved up, especially when you are doing the step up dosing, etc. afterwards it doesn't show up, but delayed neurotoxicity has been reported with CAR-T cell therapy such as Parkinson's disease, and they wonder whether the BCMA is expressed in those area, and it is an on target off tumor effect of the CAR-T cells.

Because T-cells can go into the spinal fluid, they can go into the brain. But the antibodies, they are big molecules. They usually do not cross the blood brain barrier. So delayed neurotoxicity from antibody treatment is uncommon.

Should patients be concerned about infections?

So when we use in a bispecific antibody, one arm of the antibody binds to the plasma cell. The cancer plasma cell. But the BCMA is expressed not only by the cancer plasma cells they expressed as strongly, but even the normal plasma cells express the antibody.

So when you use the antibody, you are I can say in a way you get rid of the good, the bad, the ugly, right? You get rid of the ugly, aggressive myeloma cells, you know, bad, which are the regular myeloma cells. So the cancer plasma cells are gotten, but then the good cells also get affected.

So every time you give you wipe out some of the good plasma cells. They don't come back. So the patients cannot make antibodies okay. That's number one.

Number two you know the treatment could lower the white blood count, the neutrophils. The marine soldiers which go around making sure it can fight the bacterial infection. They go down. So the patients become vulnerable for infection.

As long as they are getting it the vulnerability is there. But it is much more common when you're giving it frequently. So linvoseltamab is unique in the sense we give it weekly only for the first three months, right? And then we give it every other week. So already we reduce the frequency and after six months in majority, the patient, because there is deep response already it is given once a month. So the frequency decreases and the infection rate goes down dramatically.

So that is why we recommend that the patient get antibody IVIG when they are on bispecific antibody.

What other side effects may be seen?

Then there are other side effects which can vary according to which particular product you're using. Some of them are very common in a cancer that is lowering of the blood counts, that can happen, okay. White blood cell lowering anemia, which is a red blood cell lowering thrombocytopenia or platelet count could be lower. So lowering of the blood count is the next most common.

Then there are some additional side effects that are encountering headache. Patients do complain of headache. You know fever is very, very common is part of the cytokine release syndrome. But, you know, fever is a common symptom.

They can have occasional patient can have diarrhea is another, symptom, you know, cramping, feeling tired, exhausted. You know, after your gone through the treatment, your T-cells have been fighting the cancer cell. So you feel exhausted.

In addition to CRS, ICANS, and infection risk, the most common side effects include muscle and bone pain, nausea, headache, shortness of breath, cough, diarrhea, tiredness.

The most common severe abnormal blood results with LYNOZYFIC include low white blood cell counts and low red blood cell counts.

LYNOZYFIC can cause increased liver enzymes and bilirubin in your blood, these increases can happen with or without you also having CRS. Your health care provider will do blood tests to check your liver before starting and during treatment with LYNOZYFIC.

Tell your health care provider, if you develop any of the following signs or symptoms of liver problems: tiredness, loss of appetite, pain in your right upper stomach area, dark urine, yellowing of your skin or the white part of your eyes.

These are not all of the possible side effects with LYNOZYFIC.

What prophylactic medications are recommended when on linvoseltamab.

One thing we said the linvoseltamab, the purpose is to eliminate all the plasma cells. The good, the bad, the ugly. It gets rid of the cancer cells completely. But also the normal plasma cells are also gone. So we needed IVIG. But what about any other prophylaxis.

So as I said, the T cells are utilized to kill the cancer. So every time you give a bispecific antibody you engage the T cells to bind to the, you know, come closer to the cancer cell and kill the cancer cell. So you could deplete your T cell reserve in your body. So you can check the T cell reserve in the patient.

If the CD4 count, one of the helper T cell count is less than 200, then you can use prophylaxis such as bactrim to prevent opportunistic infection such as Pneumocystis. You know they call it PJP. It used to be PCP Pneumocystis carinae. Now they call it PJP infection okay.

The second important thing is when the T-cells are down, when you are getting this kind of thing, you also want to make sure there are prophylaxis against shingles. So they had to be on acyclovir or valacyclovir or something like that.

also you have to see if the patient is having fever or some other symptoms like diarrhea. You need to make sure the CMV is not re-activated. So you have to check the blood for the presence of CMV antigen. This can be now done routinely, not just in the transplant center or major center. It could be done.

So CMV viral reactivation is also to be checked okay. Because the patient could be vulnerable for viral infection. And you have to make sure during flu season that the patients are protected. And you recommend that they wear mask because you don't want them to get viral infection

What are your recommendations on vaccines for patients using linvoseltamab?

So first of all, you know, when you are giving a vaccine, which are important for making antibodies like, diphtheria or tetanus vaccine or a pneumococcal pneumonia vaccine, you are eliminating the plasma cells. So you're not going to make an antibody. So those vaccines don't work.

But the T-cells are important to fight viral infection. So during the flu season, I would say it is worthwhile to get antiviral flu vaccine. Now you can say is the flu vaccine going to be effective? You are educating your T-cells so that even if there is not a big robust mounting of, you know, immunity by educating them to the viral, like, you know, a flu vaccine, your body's already educated even if you get the flu, because you have previously notified your T-cell Hey, this is the vaccine for this flu vaccine for this season.

And then that particular flu comes in. I'm able to respond to it better. So I still recommend seasonal, viral vaccine.

What trial confirmed the approval of linvoseltamab?

So there was a LINKER-1 study was done. It was a phase one, two trial. And this study resulted in excellent results in the phase two portion of this drug the drug showed very good activity. Overall response rate in 70% range. Complete response rates are better 52% of the patient.

And in those patients where they looked for measurable residual disease, or MRD, they found that patients were able to achieve a MRD negative complete remission. And therefore, FDA gave an accelerated approval.

Is there a Risk Evaluation and Mitigation Strategies program for linvoseltamab?

There is a REMS program for CAR-T cell and bispecific antibodies at this time. And the REMS program basically is implemented so that the people who are going to give the antibody, they are educated, the pharmacy in that hospital or institution the physician who is going to prescribe it.

The PA or nurse practitioner who is helping the physician writing some orders as well as the nurses would be administering the drug, you know, and also the institution knows how to respond in case the patient has a side effect for the drug they're administering at that facility.

Can patients respond to linvoseltamab if they have had previous BCMA directed therapy?

BCMA is an antigen on the plasma cell. So we have a target on the plasma cell. How do you target it? There are many ways to target it.

we can have an bispecific antibody okay. We can have an antibody drug conjugate. Or we can have a CAR-T cell therapy. And each one has a different ways of happening.

If you receive CAR-T cell therapy, generally it's one and done deal. And should the cancer come back six months or a year later when the cancer comes back, they will still show BCMA on them. If that is the case. Yes, you can use linvoseltamab and it'll still work okay.

And also CAR-T cell is one and done deal. If it comes back six months or a year later your T-cells are all good to go and fight.

If you are using a bispecific antibody, you know there are two other BCMA directed bispecific antibody commercially available; teclistamab, and elranatamab. That is a little trickier and I'll tell you why.

Because we need to know why did the first BCMA bispecific fail? If it failed, Because the cancer cells, which are coming back no longer expresses BCMA, then giving another BCMA therapy is not going to work.

The second reason the BCMA is still on the cancer cell, but their T cells are exhausted by the repeated administration of other bispecific antibody. Then trying to switch is not necessarily going to work because the T cells are exhausted.

So you have to give a break in between as long as they still at BCMA positive. But you give some other treatment for a period of time, three months or so, then you will be able to go back to linvoseltamab to try to kill the cancer cells. Then it'll work, but you can't switch from one to another necessarily.

So there is an ADC you know, so the belantamab. So if you use that particular drug, you know, you can go to a bispecific because many a time when they relapse they are still expressing BCMA.

The bispecific mechanism is different. It is a T-cell redirection. It is not a drug antibody drug poison. So it would work.

What is the role of a caregiver during treatment with linvoseltamab.

During the step up dosing there is a cytokine release syndrome. So you just want to make sure somebody brings and then takes them home.

But in reality the patients they are kept overnight in the hospital at the time the doctors are going to release. They are feeling good, but somebody has once they go home, somebody has to make sure there is not a delayed reaction after they have left the home.

You know, 48 hours later they are not getting a fever or something like that. So or they are getting a little confused. So you always need a caregiver.

The caregiver is also educated. So that is they can bring them back to the center, to the doctor and provide them care.

Currently who is eligible to receive linvoseltamab?

So currently the patients who have failed four or more prior lines of treatment and those who have been exposed to proteasome inhibitor, we talked about the velcade and kyprolis or, you know, then immunomodulatory molecule.

We talked about revlimid and pomalidomide. And then anti-CD38 monoclonal antibody such as isatuximab and daratumumab.

They should have been exposed and the cancer should have come back. Then the cancer should come back at that time they can all receive linvoseltamab.

Young patients can get it. Older patient can get it. So it is not like only transplant patient can get it. And the non transplantation cannot get it.

Renal impairment is not a discrimination. Patient even on dialysis can get linvoseltamab.

So patients with extra medullary disease or patient with bone marrow with more than 50% cancer cell. So we know linvoseltamab works even in high tumor burden or extra medullary disease, etc..

This video was recorded in September 2025.

Check the manufacturer's website for the current indications for linvoseltamab.

How would a local emergency room know how to treat a patient who is having a reaction to linvoseltamab?

The patients are given a bracelet or a card to carry with them that they are receiving linvoseltamab, so that in case they got sick and they go to the nearest emergency room, those physician can call the center, the numbers are there and tell them they are on this medication.

Please call the provider and the provider. Then the physician is alerted and they can immediately engage in the management of the patient to use tocilizumab or any other appropriate medication like dexamethasone to get the patient out of trouble.

What is the LYNOZYFIC Surround Program?

Once you are prescribed LYNOZYFIC, you will have access to a dedicated patient navigational support throughout our treatment journey. When you need extra support, LYNOZYFIC Surround may be able to help.

LYNOZYFIC Surround offer financial and educational support you through out your treatment journey,.

For more information, call LYNOZYFIC Surround at .844.RGN.HEME (1.844.746.4363), Option 1, Monday–Friday, 8 AM–8 PM Eastern time.