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Multiple Myeloma an incurable disease, but I have spent the last 25 years in remission using a blend of conventional oncology and evidence-based nutrition, supplementation, and lifestyle therapies from peer-reviewed studies that your oncologist probably hasn't told you about.
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End Stage Myeloma Selinexor
End stage myeloma occurs when a MM patient reaches multi-drug resistance (MDR). Basically, if you’re a MM patient who has tried and failed all other FDA approved MM therapies then your MM grows until you die.
In my experience as a long-term cancer survivor, oncologists can focus on and standardize on the same group of chemotherapy combinations. I am posting about selinexor to post a therapy that might be out-of-the norm.
According to the study linked below, about 40% of end stage myeloma patients responded to selinexor. Of those who responded, approximately 25% “signficantly knocked down” their MM.
Selinexor in Multiple Myeloma-
Clinical Evidence of Efficacy
- STORM Study: The STORM (Selinexor Treatment of Refractory Myeloma) Phase 2b trial evaluated the efficacy of selinexor in combination with dexamethasone in patients with penta-refractory multiple myeloma (patients who had received at least three previous regimens, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody). The results showed an overall response rate (ORR) of approximately 26% with a median overall survival of about 8 months .
- BOSTON Study: The BOSTON (Bortezomib, Selinexor, and Dexamethasone) Phase 3 trial assessed selinexor in combination with bortezomib (a proteasome inhibitor) and dexamethasone versus bortezomib and dexamethasone alone in patients with relapsed or refractory multiple myeloma. The triplet combination significantly improved progression-free survival (PFS) compared to the control group. The median PFS for the selinexor group was 13.93 months compared to 9.46 months for the control group.
FDA Approval
Based on the promising results from these and other studies, selinexor received accelerated approval from the FDA in July 2019 for use in combination with dexamethasone in adults with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is resistant to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody (end stage myeloma).
Mechanism of Action
Selinexor works by inhibiting the export protein exportin 1 (XPO1), leading to the accumulation of tumor suppressor proteins in the nucleus of cancer cells. This induces apoptosis (programmed cell death) in cancer cells while sparing normal cells to a greater extent .
Side Effects and Considerations
While selinexor has shown efficacy, it is also associated with significant side effects, including:
- Thrombocytopenia (low platelet count)
- Neutropenia (low neutrophil count)
- Gastrointestinal issues (nausea, vomiting, diarrhea)
- Fatigue
- Anorexia
Patients receiving selinexor often require careful monitoring and supportive care to manage these side effects.
man hand holding his nutritional supplemets, healthy lifestyle background.
While we’re talking about outside-the-box therapies for multiple myeloma, consider integrative therapies such as intravenous vitamin C combined with melphalan. Or many other conventional chemotherapy regimens that are synergized by nutritional supplementation.
Are you a RR/MM patient looking for therapy options? End stage myeloma can be a frightening situation. Email me at David.PeopleBeatingCancer@gmail.com
Hang in there,
David Emerson
- MM Survivor
- MM Coach
- Director PeopleBeatingCancer
Recommended Reading:
- Multiple Myeloma Treatment- Managing Beyond Conventional Oncology
- Multiple Myeloma Survival – Does Depression and Anxiety Kill Patients?
- Multiple Myeloma Prognosis- Cytogenetic Prognostic Index
Unprecedented therapy found effective for blood cancer patients with no treatment options
“This trial tested selinexor with dexamethasone, a combination that significantly knocked down the cancer in more than a quarter of patients, including two patients who went into complete remission… This therapy caused at least a minimal response in almost 40 percent of patients who had multiple myeloma, a cancer of a type of white blood cell called a plasma cell.
“This study proved that a novel, first-in-class drug with a new mechanism of action can kill a patient’s cancer cells,” said the study’s senior author…”This proved that the drug worked in patients who had exhausted every other treatment and who would have been placed on hospice care otherwise.”
The clinical trial, called the STORM Part 2 Study, studied the response of 122 patients taking selinexor and dexamethasone, both oral drugs, in trials across the United States and Europe. Mount Sinai enrolled a quarter of the patients in the international study.
Patients generally saw a response to the drugs within one or two months. While there was no organ toxicity, side effects included low blood count without bleeding, nausea, vomiting, lack of appetite or fatigue.
“This study is meaningful for patients with multiple myeloma who haven’t had success on multiple other therapies…” “An increasing number of patients have resistance to the standard drugs used in the treatment of multiple myeloma, and the overall survival in these patients is short, sometimes less than three months.”
Selinexor is also being investigated in multiple myeloma in combination with other approved multiple myeloma drugs as well as in other malignancies such lymphoma and ovarian cancer…”
Oral Selinexor–Dexamethasone for Triple-Class Refractory Multiple Myeloma
“Discussion
In this trial, 26% of the patients with penta-exposed, triple-class refractory myeloma who received oral selinexor, a first-in-class XPO1 inhibitor, with dexamethasone twice weekly had a partial response or better.
Two patients had stringent complete responses, and 6 had very good partial responses. Although all patients entered the study with progressive disease, 26 (21%) had persistent disease progression or their disease could not be evaluated for response.
Among the patients who had a response, efficacy was consistent across subgroups, including patients with high-risk cytogenetic abnormalities (53% of the patients).
The results of this study are notable for several reasons. The trial was permissive, allowing patients with reduced renal function, thrombocytopenia, and neutropenia to enroll. These patients were heavily pretreated, with a median of 7 previous therapeutic regimens, including a median of 10 unique antimyeloma agents.
Patients had rapidly progressing myeloma, with a 22% increase in disease burden in the 12 days from screening to initial therapy. These characteristics are consistent with the growing population of patients who have exhausted available therapies but still desire to continue therapy.
Given the rapid progression of penta-exposed, triple-class refractory myeloma, the window of opportunity to prevent further illness and death is small. Therefore, the regimen that was used in the STORM study began with a high dose of selinexor to achieve rapid disease control. Because most patients involved in the study were older and frail, with limited end-organ reserve and at increased risk for adverse events, dose modifications were anticipated and were specified along with supportive care in the protocol.
The adverse events that were observed in the study were a function of dose, schedule, and baseline clinical characteristics (e.g., cytopenias). Thrombocytopenia, which is due in part to inhibition by selinexor of thrombopoietin signaling in early megakaryopoiesis, was reversible and was managed with dose interruptions and thrombopoietin-receptor agonists.27 Although this study establishes the activity of selinexor with dexamethasone, combination regimens are typically used in patients with myeloma. Preclinical studies of selinexor show enhancement of IκB, which supports its synergy in combination with proteasome inhibitors, additivity with immunomodulatory drugs, and sensitization of myeloma cells to anti-CD38 monoclonal antibodies.28-30
In conclusion, the results of the STORM Part 2 study showed that oral selinexor with low-dose dexamethasone induced responses in 26% of patients with refractory myeloma. The most common toxic effects of grade 3 or higher included thrombocytopenia without bleeding, anemia, neutropenia without fever, and hyponatremia.”