Lenalidomide Success Rate in Myeloma: Clear Facts, Simple Language

Lenalidomide is a routine therapy for multiple myeloma. Many are also familiar with it as the brand name Revlimid. Doctors use it to shrink the cancer, keep it under control for longer and help people live longer. But what does “success rate” mean here, exactly? Success in myeloma can be a many-splendored thing. This can mean the cancer shrinks. It can reduce the time before cancer begins to grow again. It could also mean people live longer period. This guide describes how effectively lenalidomide works in each of those types and what impacts results, as well as how dose and partner drugs modify the picture. It’s in simple, straight-to-the-point language so you can grasp the big ideas and ask good questions at your next visit.

This article is purely for educational purposes. It is not a substitute for your doctor’s advice.

What “success” looks like in treating myeloma

Doctors assess success in a few critical ways.

The response rate is the portion of people whose cancer shrinks. This could be a partial response (the amount of protein or burden of the tumor drops by at least half), and it can go deeper, to a complete response.

Time without growth is the period of time during which the cancer remains stable before it begins to grow again. This is often called “progression free survival” in many papers.

Overall Survival is the most significant endpoint. It is how long people are living from the start of treatment, regardless of what treatments they may receive afterward.

What you’ll find is that in many situations, lenalidomide passed with flying colors on all three fronts. It’s most effective when taken with other modern medications. In others, nine out of ten people react. In some it is closer to three in four. The numbers vary with the age of the patient, his or her fitness levels and stage of disease, genetics in the cancer cells and the particular mix of medicines used.

Where lenalidomide fits in the management of myeloma

There are three important times to give lenalidomide.

It is administered as the first treatment and combined with other drugs. It is employed after a stem cell transplant to help suppress the cancer, in “maintenance.” It is employed when myeloma recurs — also in a cocktail with partner drugs.

In these times lenalidomide (often) is the backbone. Drugs are stacked on top to it to increase the depth and duration of response.

First-treatment efficacy for lenalidomide in combination with dexamethasone

Most people who are not getting a transplant start with lenalidomide plus low dose dexamethasone. In a large study of more than 1,600 individuals, this two-drug approach resulted in response rates in about three in four people. The deep rate of response was approximately one in six. The period without growth was slightly more than two years on average in people who remained on treatment until their cancer grew. People also lived longer than with the previous standard melphalan, prednisone and thalidomide. These figures are derived from the FIRST study, which established a solid platform for lenalidomide in the front line.

That said, most people today are getting a third drug added and that means it gets better. We will cover those below.

Achievement rate of success, when its the part of three drug combination for IST lenalidomide

The likelihood of a deep and sustained response increases when you add an additional, modern partner drug to lenalidomide and dexamethasone. Bortezomib, a proteasome inhibitor and daratumumab, an antibody are two of the most frequent partners.

Bortezomib (Velcade) plus lenalidomide and dexamethasone is sometimes shortened to “VRd” or “RVd.” It has taken multiple trials to prove this point, but in a large trial, the above plan helped people live longer and stay in control of their lives longer versus that two-drug plan (which is just lenalidomide and dexamethasone by themselves. This is how much a three drug cocktail raises treatment success in the real-world outcomes that count most.

Daratumumab plus lenalidomide and dexamethasone is often abbreviated to “DRd.” In people who are not receiving a transplant, this combination has raised the bar. As of a follow-up period that exceeded five years, the median time without growth was about 62 months on the three drug plan for individuals and about 34 on the two. People also lived longer in general with the the three drug plan. Deeper responses were more frequent, and larger numbers of people achieved “MRD negativity,” in which disease is so low that it is essentially unmeasurable. These long term results demonstrate an excellent efficacy of lenalidomide based triplets in the frontline setting.

Patient survival if lenalidomide keeps the cancer quiet following a transplant

Following an autologous stem cell transplant, most patients go on lenalidomide maintenance to retain the gains they had from potent upfront therapy. A large meta analysis in which results from more than 1,200 patients were pooled showed that lenalidomide maintenance increased the average period of disease-free survival to nearly five years, more than doubling an earlier estimate of about two years. It also helped people to live longer in general. This is a very concrete sign of success and is why maintenance becomes a routine aspect of care.

One caveat: Long-term use may increase a small number of people’s risk for a second cancer. Doctors weigh that risk against the clear benefit of keeping myeloma in check and helping people live longer. A long term follow up to a pivotal study demonstrated both the survival benefit and small climb in second cancers thereby your group will watch for this on follow-up.

Proportion of patients achieving very good partial response or better if myeloma recurs and lenalidomide is an option

If your cancer is still sensitive to it, lenalidomide remains an anchor drug when myeloma reoccurs. By contrast, here a partner drug is typically added to a treatment response rate and duration of control go up.

Daratumumab with lenalidomide and dexamethasone has been tried in patients whose myeloma returned after they had received at least one previous treatment. In that study, the three drug plan reduced the risk of disease growth or death by more than half and extended median time without growth to about 44 months versus about 18 months with lenalidomide and dexamethasone alone.

The response rate with the three-drug combination was approximately 93%, so nearly all these patients had their cancer reduced. Many reached deep responses. This type of response rate represents a high degree of activity for lenalidomide in the context of a modern triplet at first relapse.

Carfilzomib plus lenalidomide and dexamethasone is another popular choice when myeloma returns. In a large study, adding carfilzomib extended the time without growth and improved people’s chances of living longer compared with the two-drug regimen. This demonstrates that lenalidomide can be included as a high impact combo, even after multiple prior lines of therapies.

Lxazomib plus lenalidomide and dexamethasone is an all oral alternative which also extends control duration of time. In a big study, this plan increased time without growth compared with lenalidomide and dexamethasone alone. The all oral triplet is a real plus for some people in terms of convenience.

Another option is elotuzumab plus in addition to lenalidomide and dexamethasone, which has demonstrated longer TTP compared to the two-drug regimen. It is not the most common triplet now, but it still benefits some patients.

What if the patient already has cancer that is resistant to lenalidomide?

As lenalidomide is used increasingly in the first line and maintenance settings, more people have cancers that are “lenalidomide refractory” when they relapse. Here success rate of lenalidomide containing regimens decrease. Seventy percent of doctors then shift to pomalidomide, or opt for triplets or quadruplets that don’t depend on lenalidomide. In real-world reports, outcomes are worse when the disease is lenalidomide refractory, so your care team will craft your plan on the basis of its exposure and response.

What your success rate depends on

Your starting health matters. Individuals who are in good enough shape to tolerate full dose therapy tend to have deeper responses. Success is not precluded by age. In long-term follow-up, the daratumumab lenalidomide dexamethasone regimen actually worked across all ages — including those 75-plus and even 80-plus.

The cancer’s genetics matter too. Certain high-risk features decrease the probability and duration of response to any drug mixture. Still, many people with high risk changes do just fine with strong triplets or quadruplets, and your team may choose a plan keeping in mind this possibility.

Whether you end up with a transplant can change the path too. After a transplant followed by lenalidomide maintenance, people often have a very long period in which the disease remains under control. Patients who do not receive a transplant can still fare very well with a modern three drug regimen based on lenalidomide.

Standard doses of lenalidomide and why they differ

Lenalidomide comes in several strengths. The most common ones used in myeloma are 5 mg, 10 mg, 15 mg and 25 mg.

The most frequent initial dose in a combination for active myeloma is 25 mg once daily on days 1–21 of a 28 day cycle with dexamethasone. If you would like to find more information on that strength then please read about Lenalidomide 25mg. This regimen is included in the official product information and world-wide package inserts. The dose is adjusted in response to side effects, age, kidney function and blood counts.

For maintenance after a transplant, many people begin at 10 mg a day and can increase to 15 mg daily after approximately three months if it is well tolerated and blood counts are stable. More information can be read in publications regarding Lenalidomide 10 and Lenalidomide 15. These ranges reflect how maintenance was administered in large trials and how many centers write their protocols at the present time.

If blood counts fall, if there are stomach problems, a rash or the kidneys do not work as well, the dose can be reduced. Some are able to taper the doses down to 5 mg daily or every other day. You can learn more about low dose usage here: Lenalidomide 5mg. Your team will tell you how much medicine to take, so that it keeps the cancer in check but does not harm you.

Potential common side effects to look for

Like all cancer drugs, lenalidomide has side effects. The most frequent ones are low white blood cells, low red blood cells, low platelets, fatigue, diarrhea and rash. Blood clots may develop, so doctors commonly use blood thinners when the risk of clots is high. Such risks, though, are part of the reason why the dose and schedule get adjusted over time. These effects are listed in the official product information and how doctors address them.

A small number of patients may get a second cancer from long-term use of lenalidomide as maintenance. Your team will balance that risk against powerful benefits in holding myeloma at bay and improving survival, with the help of careful monitoring plans.

Putting the numbers together

If you step back and stare at the big picture, a pattern emerges. Lenalidomide, with or without dexamethasone, induces most patients to respond and holds the disease quiet for years. Add a contemporary partner drug, and the success rate is even higher. In a first treatment without a transplant, a lenalidomide-based triplet with daratumumab can control myeloma for a median of approximately five years or more; — and it also improves how long people live. As maintenance after transplant, lenalidomide at least doubles the average interval before the disease regrows and extends survival. At relapse, lenalidomide based triplets achieve very high rates of response and prolong control. These are robust, replicable gains across settings.

How to use this information

You can use this information to make a plan with your care team. Inquire which of our plans best suits your circumstances.” Ask how your kidney function, your bone marrow and the genes of your cancer might alter what dose or other drugs should be used. Ask what the plan is to prevent blood clots. Inquire about how long you will be on therapy and what the plan is should your cancer return later.

If you are wondering about capsule strengths and real life use, read here: Lenalidomide 5mg, Lenalidomide 10mg, lenalidomide 15mg and lenalidomide 25 mg.

Conclusion

Lenalidomide has defined modern multiple myeloma care. It can also help most people respond by itself or with dexamethasone. When coupled with potent partner drugs, it offers longer control times and higher odds of the deep, durable responses that define effective cancer treatment. Following a transplant, it assists people in maintaining remission longer and in living longer.

The actual rate of success will depend on your health and features of your myeloma, as well as which combination of medicines you used. For those treated with the correct partners and at appropriate doses, lenalidomide is still one of quite the best wins in myeloma care today. Start with this guide, take your questions to your care team and develop a plan that works for your goals and life.

FAQs

What is a good response rate for lenalidomide combinations?

In the majority of people in traditional three drug plans, cancer shrinks. At relapse, the response rate exceeded nine in 10 with lenalidomide, daratumumab and dexamethasone. Many reached very deep responses. In 1st Tx no TRS, GL was given on all three drugs induced deeper and more lasting responses than in 2nd Tx.

How long can lenalidomide control myeloma?

The lenalidomide daratumumab dexamethasone plan which people in this group didn’t receive a stem cell transplant with, kept the myeloma under control for a median of around 62 months while the two drug plan was around 34 months. Lenalidomide maintenance, post-transplant, also more than doubled time without growth to approximately 53 months in a large pooled study. On a personal basis the results vary greatly, but these are sturdy guideposts.

Do people who take lenalidomide live longer?

Yes. The addition of partner drugs such as daratumumab or carfilzomib to lenalidomide has resulted in longer overall survival in large studies. Maintenance therapy with lenalidomide after transplant has also been associated with a survival benefit in aggregated data. In other words, more people are alive many years after signing up for these plans.

At what amount does the average person begin with?

For active combination 25 mg daily on days 1–21 of a 28 day cycle is the starting dose for many. Post-transplant, most begin maintenance therapy at a dose of 10 mg daily and can be increased to 15 mg if tolerated. If there are safety concerns, dose can be reduced to 5 mg. Your doctor will adjust depending on your counts and how you are feeling.

What if my myeloma is resistant to lenalidomide already?

If you are lenalidomide refractory, the efficacy of lenalidomide containing regimens goes down. Your team probably will switch to pomalidomide or other backbones or antibodies and new class drugs. Real world reports indicate that outcomes are poorer once the disease becomes refractory to lenalidomide, so plans change in accordance with reality.