The combination of Selinexor, Carfilzomib, and Dexamethasone, known as SKd, is a targeted treatment regimen for multiple myeloma. This therapy is for adult patients whose cancer has returned or has not responded to previous treatments. The regimen combines three different drugs that work together to combat cancer cells, with each component having a distinct function.
How the Three-Drug Combination Works
The effectiveness of the SKd regimen comes from the complementary actions of its three components. Each drug targets a different process within the cancer cells, creating a multi-pronged attack. This approach can be more successful than using any single drug on its own, as it makes it more difficult for cancer cells to survive and multiply.
Selinexor is a first-in-class medication known as a Selective Inhibitor of Nuclear Export (SINE). It works by blocking a protein called exportin 1 (XPO1). In multiple myeloma, XPO1 is overactive, pushing important tumor-suppressing proteins out of the cell’s nucleus where they cannot function. Selinexor traps these tumor suppressor proteins inside the nucleus, allowing them to resume their natural function of controlling cell growth and initiating cell death in cancerous cells.
Carfilzomib belongs to a class of drugs called proteasome inhibitors. The proteasome acts as a cellular recycling center, breaking down and disposing of old or damaged proteins. Cancer cells produce large amounts of abnormal proteins and are highly dependent on the proteasome to clear this waste. Carfilzomib blocks the proteasome, causing a toxic buildup of these proteins inside the myeloma cell, which ultimately triggers cell death.
The third drug, dexamethasone, is a corticosteroid with well-established anti-inflammatory and anti-cancer properties. It can directly induce the death of myeloma cells, reduce inflammation in the body that can be associated with cancer, and help manage some of the side effects of the other chemotherapy agents. The synergy between the three drugs creates an effective combination.
Patient Candidacy for Treatment
The SKd therapy is intended for adult patients diagnosed with multiple myeloma that is either relapsed or refractory. Relapsed myeloma means the cancer has returned after a period of improvement, while refractory means the cancer did not respond to the initial treatment or has stopped responding. This combination is considered for patients who have already undergone previous treatments for their condition.
Eligibility for the SKd regimen depends on the number and type of prior therapies a patient has received. It is approved for patients who have had at least one to three previous lines of therapy. This means the individual has tried other treatments that were either not effective enough or have ceased to be effective over time.
Certain pre-existing conditions or specific characteristics of the myeloma may influence whether a patient is a suitable candidate. For instance, patients who are refractory to carfilzomib may be excluded from this specific combination. A patient’s kidney function, blood counts, and overall performance status are also taken into account before starting treatment.
The Treatment Regimen
The administration of the Selinexor, Carfilzomib, and Dexamethasone regimen is structured around a 28-day cycle. A notable aspect of this combination is its once-weekly schedule for all three medications. This less frequent dosing can be more convenient for patients compared to older regimens that required more frequent visits to the clinic. The treatment cycle is repeated as long as the patient is benefiting from the therapy and the side effects are manageable.
Selinexor and dexamethasone are both oral medications, taken as pills. Carfilzomib is given as an intravenous (IV) infusion at a hospital or treatment center. The infusion itself is relatively short, but the overall appointment time will include preparation and observation periods.
To help prevent and manage potential side effects associated with the IV infusion of carfilzomib, patients receive supportive care medications beforehand. This can include hydration fluids and other drugs to minimize infusion-related reactions. The specific doses of each of the three drugs may be adjusted by the oncologist based on how well the patient tolerates the treatment.
Navigating Potential Side Effects
The SKd regimen can cause side effects, and managing them is an important part of the overall care plan. The side effects can vary from person to person in their type and severity. Open communication with the healthcare team is necessary to address any issues that arise promptly.
Some of the most frequently reported side effects include fatigue, nausea, and a decrease in appetite. These are often most noticeable in the days following treatment. To manage nausea, anti-nausea medications are prescribed. Maintaining good nutrition and hydration can also help combat fatigue and poor appetite. Small, frequent meals may be easier to tolerate than large ones.
The treatment can also affect blood cell counts, which are monitored regularly through blood tests. A common hematologic side effect is thrombocytopenia, which is a low level of platelets. Platelets are important for blood clotting, so a low count can increase the risk of bruising or bleeding. Other blood counts, such as red blood cells (anemia) and white blood cells, can also be affected. If blood counts drop too low, the medical team may adjust the dose or temporarily pause treatment.
Clinical Efficacy and Outcomes
The effectiveness of the Selinexor, Carfilzomib, and Dexamethasone combination has been evaluated in clinical trials. The BOSTON study provided data on the regimen’s performance in patients with relapsed or refractory multiple myeloma. This trial compared the once-weekly SKd regimen to a twice-weekly treatment of bortezomib (another proteasome inhibitor) and dexamethasone.
In one study, the overall response rate (ORR), which is the percentage of patients whose cancer showed a significant response to the treatment, was 78.1%. This included patients who had a complete response, a very good partial response, or a partial response.
An important metric in cancer treatment is progression-free survival (PFS), which measures how long a patient lives without their disease getting worse. The median PFS in one study was 15 months. The studies also noted that the side effects were generally manageable, making the combination a valuable treatment option for previously treated patients.