“Bortezomib with dexamethasone as first-line treatment for AL amyloidosis with renal involvement…in multiple myeloma or MGUS patients?”
You’ve been diagnosed with multiple myeloma (MM) AL amyloidosis. Your oncologist tells you that the standard protocol is an autologous stem cell transplant (ASCT). The issue that sticks in your mind is that by all diagnostic measures, your MM, the amount of monoclonal proteins in your bone marrow is low.
By low, I mean-
- normal immunoglobulins, just above normal?
- normal freelight chains, just above normal?
- monoclonal proteins level below 3.0
- maybe no CRAB symptoms?
Your issue is that the small amount of MM in your marrow is making a protein called amyloid. The little proteins are clogging up you heart and/or kidney causing real health problems for you.
What do you do?
Your decision-making may be affected by your age, diagnostic testing (discussed above) and overall goals. Many people I work with are younger than the average MM patient (69 years of age) and don’t want to undergo an aggressive, high toxicity procedure like an ASCT.
According to the first study linked below, Bortezomib with dexamethasone can be an effective therapy for you yet with much less toxicity, much less chemotherapy.
Further, an ASCT can produce a complete response in %33-%37 of patients, and according to the first study linked and excerpted below, Bortezomib, dexamethasone achieves a 45% complete response? Why then, is an ASCT “standard-of-care” therapy for newly diagnosed MM AL amyloidosis patients?
Consider also, that curcumin has shown the ability to enhance the efficacy of Bortezomib while protecting kidney health.
My role is not to tell you what to do. My role is to inform you of the pros and cons of different forms of therapy. For more information about evidence-based, non-toxic MM therapies, scroll down the page, post a question or comment and I will reply to you ASAP.
Thank you,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Recommended Reading:
“Although bortezomib has reported efficacy in light chain (AL) amyloidosis, the role of bortezomib in combination with dexamethasone (BD) as the first-line treatment for patients with AL amyloidosis has not been determined.
We analyzed the outcomes of 72 consecutive unselected patients, which received primary therapy with BD in a single center.
The patients were newly diagnosed with AL amyloidosis with
- renal (100%),
- cardiac (72%),
- hepatic (19%) or
- nervous system (10%) involvement
and underwent a median of 2 (1-6) cycles of BD treatment.
A hematologic response was achieved in 75% of the patients within a median period of 2 months, and 45% of those patients achieved a complete response.
A renal response was achieved in 50% and 60% of patients at 1 year and 2 years, respectively, and a cardiac response was achieved in 40% and 46% of patients at 1 year and 2 years, respectively.
After a median follow-up period of 24 months, the median duration of progression free survival was 45 months, and the estimated overall survival rates at 12 and 24 months were 83% and 76%, respectively.
Baseline Eastern Cooperative Oncology Group performance status and proteinuria were associated with overall survival. The BD regimen induced high rates of rapid hematologic and organ responses in AL amyloidosis patients…”
“What is amyloidosis?
Amyloidosis represents a group of disorders characterized by deposition of insoluble protein fibrils (amyloid) into the patient’s organs, leading to dysfunction.
Although technically classified as a rare disease, amyloidosis has three distinct subtypes –
- AL (primary),
- AA (secondary),
- and ATTR
About 4,000 new cases are believed to be diagnosed annually in the United States alone.1
The most common subtype of amyloidosis, the AL type, has an estimated prevalence rate of 40.5 cases per million person years, and the incidence has been steadily increasing at the rate of 12% per year.2
With rising statistics, the disease remains poorly understood, and concerns remain about the current methods of managing this condition.
How is amyloidosis diagnosed?
Amyloidosis diagnosis can be challenging. Indeed, 20% of AL amyloidosis patients experience a delay in diagnosis by as much as two years, while the wait is around 42% in patients suffering from the cardiac ATTRwt subtype of amyloidosis.3 While case history and clinical evaluation are taken into account, diagnosis is primarily made through a tissue biopsy.
Once diagnosed, clinical subtyping of the disease is necessary, as this forms the basis of the management strategy. Another factor to be considered is the severity of amyloid-related organ dysfunction, especially advanced cardiac complications.4
Once identified, the focus of treatment is to rescue organ function by suppressing the production of amyloidogenic free light chains (FLCs) and to minimize treatment-related mortality and morbidity.
What is the current state of AL amyloidosis management?
For AL amyloidosis, a risk assessment is usually performed at the outset to inform management. The risk assessment primarily takes cardiac status into account, but also considers
- peripheral neuropathy,
- renal status and
- lung disease…
Today, low risk patients, who comprise about 20% of all AL amyloidosis patients, are managed with Autologous Stem Cell transplantation (ASCT). While initially associated with high mortality rates, careful risk assessment and patient selection has decreased mortality. ASCT can produce complete response in 35-37% of all patients, and hematological response in 71% of patients.7
Are there any novel treatments for AL amyloidosis?
ASCT is highly dependent on patient selection. Novel treatments are emerging for patients who do not meet the selection criteria, as well as for intermediate or high-risk patients.
Velcade (bortezomib), a proteasome inhibitor, is becoming increasingly common as a pre-induction therapy before ASCT, or for ‘consolidation’ after ASCT treatment.
Bortezomib is also effective as monotherapy, but combinations with dexamethasone have shown better rates of progression-free survival.8
Novel treatments have also looked at replacing the use of Alkeran (melphalan) in intermediate risk patients, who form about 65% of all AL amyloidosis patients. Bortezomib in combination with cyclophosphamide and dexamethasone can provide a hematological response rate of 81%, which is comparable to bortezomib and Mdex, and superior to Mdex alone.9…
Low-dose treatment with bortezomib is preferred and, if tolerated, newer therapeutic agents may be introduced.11
Several novel drugs have been introduced for patients with relapsed or refractory disease.
- Thalidomide derivatives, including
- Revlimid (lenalidomide) and
- Imnovid (pomalidomide)
- have demonstrated reasonable hematologic response rates.
However, lenalidomide has been associated with renal dysfunction at higher doses.12
A new, oral proteasome inhibitor, Ninlaro (ixazomib), has shown promise in relapse-refractory AL. It has also been shown to achieve a hematologic response in 52% and an organ response in 56% of patients.12
Are there any investigational treatments for AL amyloidosis?
A proteasome inhibitor, Kyprolis (carfilzomib), is currently being evaluated for AL amyloidosis patients who have peripheral neuropathy (Clinicaltrials.gov: NCT02545907)…”
