Hope for Multiple Myeloma Patients
- A new drug combination for treating multiple myeloma (MM) has shown a major increase in survival for patients whose cancer has relapsed, or returned.
- The new drug combination was powered by the drug Isatuximab, also known as Sarclisa.
- The three-drug combination can extend the time a relapsed patient’s cancer goes without growing, otherwise known as progression-free survival, by over 20 months.
- One of our experts says that this drug combination “is another useful tool for treating relapsed and refractory multiple myeloma.”
When your multiple myeloma comes back after your treatment left you cancer-free for a while, it is termed relapsed multiple myeloma. There are currently many exciting new agents available for relapsed multiple myeloma with one being the recently studied combination therapy powered by the drug Sarclisa. An FDA analysis of the study’s data found that this combo gave patients a much longer progression-free survival of 41.7 months compared to the 20.8 months of progression-free survival with the standard drug combination.Read More
But before we take a look at the research surrounding the Sarclisa as a part of a new three-drug combination, let’s get a better understanding of multiple myeloma and the treatment options out there today.
Understanding Multiple Myeloma
Multiple myeloma, in general, is a blood cancer involving plasma cells — a certain kind of mature white blood cell in the bone marrow that helps fight infection by producing proteins that help your immune system fend itself against germs.
The bone marrow makes red blood cells which bring oxygen to our tissues, white blood cells which fight infections and platelets which help stop bleeding. For people with multiple myeloma, cancerous plasma cells, or myelomas, grow uncontrollably in the bone marrow and crowd out healthy white blood cells. This, in turn, inhibits the immune system’s ability to fight off infection which can lead to fatigue.
Eventually, the myelomas grow too large in the bone marrow which can cause bone fractures. Myelomas can also lead to kidney damage because these cancerous cells release abnormally high levels of antibodies into the bloodstream which eventually build up in the kidney since its unable to process these extra proteins.
Current Treatment Options for Multiple Myeloma
Unfortunately, there is still technically no cure for multiple myeloma, and the cancer may progress despite multiple rounds of chemotherapy. When it comes back (relapses), you are going to face decisions about which treatment to choose because there is no single standard of care.
The goal in relapsed multiple myeloma is to use newer treatments that were not used after the initial diagnosis. From a prior survivornet interview with Dr. Vincent Rajkumer, medical oncologist at the Mayo Clinic, “I would say that most of us would prefer a monoclonal antibody-based combination for the first relapse.”
The treatment is usually a three-drug or two-drug combination therapy that can include:
- A proteasome inhibitor – targets the enzyme that breaks down proteins in cancer cells and causes the cells to die.
- a monoclonal antibody – targets various antigen receptors on the cancer cells in order to destroy myeloma cells.
- Dexamethasone – a steroid drug that prevents inflammation and associated pain from myeloma, and it can even help kill myeloma cells at high doses.
A New Standard of Care: Adding Sarclisa to Treatment
Now let’s dive into the new treatment option being studied for multiple myeloma patients who’ve relapsed. In a recent phase 3 clinical trial (IKEMA trial) for patients who had received one to three previous lines of multiple myeloma therapy, the addition of Sarclisa (Isatuximab) to the drug combination carfilzomib–dexamethasone (referred to as I-Kd) showed great promise compared to the standard treatment combo of carfilzomib–dexamethasone (Kd) on its own.
In a statement for SurvivorNet, Dr. Andrew Yee, the clinical director of the center for multiple myeloma at Massachusetts General Hospital Cancer Center, shared his take on the study.
“The IKEMA trial establishes the efficacy of adding isatuximab to carfilzomib and dexamethasone,” Dr. Yee recently told SurvivorNet. “The combination is another useful tool for treating relapsed and refractory multiple myeloma.
“Recently, the results of the trial have been updated at the ESMO meeting in May, where the triplet combination showed a PFS (progression-free survival) of 35.7 months v. 19.2 months in the control arm. The updated results now show a significant improvement in PFS in lenalidomide-refractory disease, which is increasingly relevant given that majority of patients in our practice are treated with lenalidomide maintenance until progression.”
To get into more of the specifics, all of the 302 multiple myeloma patients in the study had undergone one to three prior lines of therapy and were randomly assigned to receive either a combination of two drugs: Kyprolis and dexamethasone (Kd) or the new combination of Kd with Sarclisa (I-Kd). Half of the patients took the three-drug combination; the rest underwent standard two-drug chemotherapy.
Sarclisa was administered through the vein once a week for four weeks, then every other week for 28-day cycles. This was given in combination with carfilzomib twice a week and dexamethasone at the standard dose for the duration of treatment. These patients were treated until cancer progressed, developed any side effects, or until patients decided to come off the study.
How Does Sarclisa (Isatuximab) Work?
Sarclisa (Isatuximab)is a monoclonal antibody that binds to a specific part of the antigen on myeloma cells specifically CD38 receptor on multiple myeloma cells. CD38 receptor is usually present on the surface of multiple myeloma cells, making it a suitable target for this drug. The drug works against the disease in several ways, including stopping the growth of tumor cells and programming their death.
Sarclisa is approved in a number of countries (including the U.S. and EU) in combination with pomalidomide or kyprolis, and dexamethasone for the treatment of patients with MM who progressed on 2 or more prior treatments. Pomalidomide is an anti-angiogenic and also acts as an immunomodulator, blocking angiogenesis and myeloma cell growth. Cancer patients being given chemotherapy can be given dexamethasone to work against some side effects.
The IKEMA Trial: “Unprecedented” Survival Results
The primary goal of the study was to look at PFS (progression-free survival) meaning the time from a random assignment in the trial to disease progression or death from any cause. Below are some key takeaways regarding the findings of this trial:
- In patients who took the three-drug combination (I-Kd) treatment, cancer stopped growing for about 35.7 months, as compared with 19 months for those with standard chemotherapy.
- The study also found an improvement in the second update on progression-free survival (PFS2) analysis reflecting the long-lasting effect of the combination drugs.
- In addition, In addition, the patients who were treated with combination therapy had no detectable cancer in the body with minimal residual disease (MRD)-negative status. An MRD test is done to look for any cancer cells that were not killed by chemotherapy. For example, if you have any cells found in that one million, you’re MRD positive, but if they find no cells in that million, you’re MRD negative. MRD negative is where you want to get to and should be the goal of your treatment.
- The researcher described the combination drugs (I-Kd) as well tolerated and was consistent with the previously observed side effects for Sarclisa.
- Additionally, the FDA did their own analysis of the study’s data based on their own criteria for patients – otherwise known as censored data analysis – and found that the I-Kd group had a much longer progression-free survival of 41.7 months and the patients treated just with Kd had progression-free survival of 20.8 months.
Dr. Nina Shah, the hematologist-oncologist at the University of California, San Francisco, previsously quoted, added her thoughts on the study results in a statement for SurvivorNet.
“In general these data support the use of isatuximab and carfilzomib for patients with RRMM (relapsed/refractory multiple myeloma) in the 1-3 prior line setting,” Dr. Shah wrote in an email. “The PFS we are seeing with this therapy is among the best we have seen of any combination in the 1-3 prior line of therapy, suggesting that the combination of anti-CD38 antibody with carfilzomib is a potent one.
“While considerations always need to be made ie: cardiovascular function and tolerance for anticipated side effects like low blood counts and immunosuppression, the benefit hugely outweighs the risks. We look forward to a longer follow-up.”
What Does This Trial Mean For Me?
If you have been diagnosed with multiple myeloma, the results of this study are extremely exciting and promising. This combination therapy is now the FDA-approved current standard of care that can be used if your cancer returns after primary treatment.
“This drug, isatuximab, was approved in March 2020 for patients who have received at least two prior therapies, but now doctors may have the opportunity to prescribe it after one prior line of therapy,” Dr. Shah said in a previous interview with SurvivorNet. “This is something people can ask their doctors about, particularly if they’re having their first relapse.”
Perhaps most importantly, this trial is yet another reminder that one size doesn’t fit all.
For Dr. Francesca Gay of the University of Turin in Italy, the results add to a treatment landscape for relapsed myeloma that has become increasingly complicated by the availability of multiple options for different scenarios within the relapsed setting.
Therefore, it is very important to have a discussion with your physician to guide you to choose your therapy from different available standard care treatment options.
“I think that it’s very difficult for us as clinicians to try to put all this data together and to try to understand what can be the best option for each patient,” Dr. Gay said. “The good thing is that there are several options that we can consider.”
Newer medications may be a possibility for people whose cancer returns after treatment. And this combination treatment, so far, provides the longest PFS benefit in relapsed myeloma patients.
“To observe progression-free survival of more than three years in patients with relapsed multiple myeloma when isatuximab was added to a proteasome inhibitor backbone of therapy is unprecedented and reinforces our confidence in isatuximab as a potentially best-in-class anti-CD38 antibody,” said Dr. Peter C. Adamson, the Global Head of Oncology Clinical Development and Pediatric Innovation at Sanofi – the pharmaceutical company in the recent press release on Sarclisa.
What Questions to Ask Your Doctor:
If you have or a loved one has been diagnosed with relapsed MM, it’s important to be prepared and informed about your disease process. Upon diagnosis, you may want to ask questions for possible different circumstances such as:
- What will my treatment cost?
- How many times a week do I need to come to the clinic for the treatment?
- How will I feel during treatment?
- Will I have side effects that last after the treatment?
- How will treatment affect my life?
- How many people have you treated with these combination medicines who had the first relapse?
- Should I get a second opinion?
- What are the advantages and disadvantages of combination three-drug chemotherapy (I-Kd) versus two-drug (Kd) treatment?
- What survivorship support services are available to me? To my family?
- What is my prognosis?