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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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High-Risk Multiple Myeloma

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High-Risk Multiple Myeloma- Common myeloma is difficult to treat. High-Risk myeloma means that the newly diagnosed patient has genetic differences compared to the average patient. These genetic differences make the patient’s myeloma more difficult to treat with both shorter progression-free survival (PFS) and overall survival (OS) times shorter.

High-risk myeloma is defined as:

“High-risk multiple myeloma was defined by one of the following: gene expression profiling high risk (GEPhi), t(14;16), t(14;20), del(17p) or amp1q21, primary plasma cell leukaemia and elevated serum lactate dehydrogenase (two times the upper limit of normal or more)…”

Ultra high-risk myeloma is defined as:

“UHiR disease, defined by presence of ≥2 genetic risk markers t(4;14)/t(14;16)/t(14;20), del(1p), gain(1q), and del(17p), and/or SKY92 gene expression risk signature…”

According to research, 10-20% of newly diagnosed myeloma (NDMM) patients are high-risk. 

What’s the high-risk myeloma patient to do? According to the three studies linked and excerpted below, conventional oncology has one basic idea. Give the NDMM patient a great deal of chemo in hopes of achieving the deepest possible remission which should result in a longer progression-free survival than the NDMM patient would achieve, on average, if he/she underwent the standard-of-care regimen for MM which is D-VRd f0llowed by a single SCT.

It is not clear to me what the average OS would be or the patient’s risk of adverse events otherwise know as side effects.

If you have been diagnosed as high-risk, I thinks it is important for you to understand how MM patients are diagnosed and staged-

I’ve spent years counseling MM patients on the dangers of toxicity. And here I am writing a blog post about how huge amounts of chemotherapy/toxicity is high-risk MM patient’s main choice.

Are you a “high-risk” MM patient? Or ultra high-risk? Scroll down the page, post a question or a comment and I will reply to you ASAP.

Hang in there,

David Emerson

  • MM Survivor
  • MM Cancer Coach
  • Director PeopleBeatingCancer

Daratumumab, Cyclophosphamide, Bortezomib, Lenalidomide, and Dexamethasone as Induction and Extended Consolidation Improves Outcome in Ultra-High-Risk Multiple Myeloma

“PURPOSE-The multicenter OPTIMUM (MUKnine) phase II trial investigated daratumumab, low-dose cyclophosphamide, lenalidomide, bortezomib, and dexamethasone (Dara-CVRd) before and after autologous stem-cell transplant (ASCT) in newly diagnosed patients with molecularly defined ultra–high-risk (UHiR) multiple myeloma (NDMM) or plasma cell leukemia (PCL). To provide clinical context, progression-free survival (PFS) and overall survival (OS) were referenced to contemporaneous outcomes seen in patients with UHiR NDMM treated in the recent Myeloma XI (MyeXI) trial…

Bortezomib, lenalidomide, and dexamethasone with or without elotuzumab in patients with untreated, high-risk multiple myeloma (SWOG-1211): primary analysis of a randomised, phase 2 trial

Background- The introduction of immunomodulatory agents, proteasome inhibitors, and autologous haematopoietic stem-cell transplantation has improved outcomes for patients with multiple myeloma, but patients with high-risk multiple myeloma have a poor long-term prognosis. We aimed to address optimal treatment for these patients…

High-risk multiple myeloma was defined by one of the following: gene expression profiling high risk (GEPhi), t(14;16), t(14;20), del(17p) or amp1q21, primary plasma cell leukaemia and elevated serum lactate dehydrogenase (two times the upper limit of normal or more)…

Interpretation- In the first randomised study of high-risk multiple myeloma reported to date, the addition of elotuzumab to RVd induction and maintenance did not improve patient outcomes. However, progression-free survival in both study groups exceeded the original statistical assumptions and supports the role for continuous proteasome inhibitors and immunomodulatory drug combination maintenance therapy for this patient population…”

Outcomes of Tandem Hematopoietic Stem Cell Autologous Transplant in High-Risk Myeloma Patients: A Single-Center Experience

Introduction: Studies have demonstrated that multiple myeloma (MM) is a clinically, genetically complex and heterogeneous disease. Cytogenetic alterations identify high-risk patients in MM and are associated with a poor prognosis. They include at least one of the following at diagnosis: t(4;14), t(14;16), t(14;20), del(17p), 1q amp and 1q amp + del(1p). Autologous stem cell transplantation (ASCT) and the development of novel agents have considerably increased the median survival of MM patients. Patients with high-risk cytogenetics are associated with worse survival, and studies have shown improvement in progression-free survival with tandem ASCT when compared to single ASCT…

Results: From January 1, 2017, to December 31, 2020, 25 high-risk patients underwent tandem ASCT…

At the median follow-up time of 60 months,

  • 44% of patients had relapsed.
  • 1 patient relapsed within 1-3 months post ASCT#1.
  • Nine other patients relapsed post ASCT #2 and maintenance except one patient who relapsed at time of ASCT #2.

Univariable analysis identified hemoglobin as a statistically significant association with risk of progression or death. All patients who received any maintenance after tandem transplant were progression-free at 60 months (p<0.001).

Conclusion: In our retrospective study, results suggest that tandem ASCT allows for deepening of responses. Together with maintenance therapy, this contributes to the durability of further PFS prolongation in high-risk MM patients…”

Quadruplet Produces Deep Responses in High-Risk, Newly Diagnosed Multiple Myeloma

“Isatuximab plus carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) can produce deep responses in patients with high-risk, newly diagnosed multiple myeloma (NDMM)…

The study included transplant-eligible and -ineligible patients who received Isa-KRd as induction and consolidation. Both patient groups had deep responses after consolidation, with a majority of patients achieving minimal residual disease (MRD) negativity…

The safety population included 122 patients — 97 transplant-eligible and 25 transplant-ineligible patients. Grade 3 or higher treatment-emergent adverse events occurred in 78.4% of the transplant-eligible group and 72% of the transplant-ineligible group.”



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