Multiple Myeloma survival (and prognosis) varies depending upon a host of factors: the stage of disease, biology including cytogenetic abnormalities and response to therapy.
When it comes to a diagnosis and then the prognosis of multiple myeloma, sometimes I wonder if “ignorance is bliss.” I wonder about this idea because when I was diagnosed with MM in early ’94, the study of cytogenetics and molecular subtypes for MM hadn’t been researched. I was told that I was non-secretory and that was that.
I barely responded to my induction therapy and relapsed in less than a year after my autologous stem cell transplant.
To put it another way, the prognosis of a newly diagnosed MM patient varies a great deal from patient to patient. However, I will list the key factors:
- Stage (MGUS, SMM or frank MM of I, II or III)
- Age of the patient- the average age at diagnosis is 67. MM patients in their 50’s weather toxicity much better than MM patients in their 70’s-
- Overall health of the patient
- MM Specialist- this last prognostic indicator will be controversial among non-specialists. MM specialists offer an average prognosis that is way ahead of non-specialists…
- Genetic abnormalities
The first three prognostic indicators can be handled by hematologist-oncologists. Meaning, it doesn’t take a MM specialist to juggle the patients stage, age and overall health. However, newly diagnosed MM patients who present with one or more genetic abnormalities will definitely benefit from working with a MM specialist.
After excerpting the list of MM facts and statistics listed on the “stardardofcare.com” website in order to list all of the related facts/stats/etc. that pertain to MM cytogenetics, I found myself wondering if my own MM had some sort of genetic abnormality. According to Non-secretory myeloma: a clinician’s guide, I may have had a genetic abnormality but, according to the study, “there is no reason to think that non-secretory outcomes will be appreciably worse...”
The good news is that a diagnosis of MM today (2019) will give the newly-diagnosed patient much more diagnostic information to go on. The bad news is that oncology doesn’t always know that much about what MM cytogenetic information means for the MMer.
I am a long-term MM survivor and MM cancer coach. The one thing I’m sure of is that MMers need to ask the right questions based on their stage, biology, cytogenetics, and response to therapy. Please scroll down the page, post a question or comment and I will reply to you ASAP.
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Dr. Stephen Cohen- Standard Of Care
Have you ever wanted to read the notes and observations of a practicing compassionate and empathetic doctor who has cared for cancer patients for over 40 years? Well, now you can! Dr. Stephen Cohen, a medical oncologist and hematologist practicing in San Antonio, Texas, has kept a daily journal of interesting medical info and tidbits he encounters day to day from his personal experiences with patient care, professional journals he reads, and medically relevant information on all subjects that he comes across.
- Myeloma survival varies depending upon a host of factors: the stage of disease, biology including cytogenetic abnormalities and response to therapy.
- Disease biology is reflected in the molecular subtype of myeloma and the presence or absence of secondary cytogenetic abnormalities.
- Chromosome abnormalities detected with cytogenetics or fluorescence in situ hybridization in more than 90% of cases and include deletions, trisomies, and translocations.
- Approximately 40% of myeloma cases characterized by trisomies it in the neoplastic plasma cells, while most of the rest have a translocation involving the immunoglobulin heavy chain locus on chromosome 14q32 (IgH translocated MM).
- A small proportion of patients have both trisomies and IgH translocation.
- Trisomies and IgH translocations are considered primary cytogenetic abnormalities and occur at the time of the establishment of MGUS.
- Secondary cytogenetic abnormalities arise during the disease include gains, deletions etc.
- At least 50% of patients with clonal plasma cell proliferation in monoclonal gammopathy of unknown significance (MGUS) translocations involving the immunoglobulin heavy chain (IgH) locus on chromosome 14q32 evolve into myeloma.
- Hyperdiploidyand IgH translocations are early events in disease pathogenesis, and del(17p13) and translocations of MYC locus are late events.
- Patients with t(4; 14) derive substantial benefit from proteasome inhibitors.
- Hyperdiploidy and is observed in 50-60% of patients, while monosomy is seen in 45% of cases.
- Recurrent structural rearrangements are seen in the IGH gene mapped as 14q32.
- Early translocations in chromosomes occur at immunoglobulin switch region on chromosome 14(q32,33), and this most commonly juxtaposed to MAF (t[14:16][q32,33:23] and MMSET on chromosome 4p16.3.
- The above causes deregulation of 2 adjacent chromosomes MMSET, in all cases and FGFR3 in 30% of cases.
- Abnormalities in t(4;14) and t(14;16), and loss of 17p13 confirmed poor prognosis with high dose therapy.
- Deletion 17p suggests a low likelihood of long-term disease control with traditional approaches of induction, consolidation, and maintenance.
- Overall survival for patients with 17p deletion has half the survival than patients who do not have that.
- Hyperdiploidy associated with better outcomes to treatment, with older age at presentation, with IgG kappa protein and with more indolent forms of myeloma.
- Hypodiploid subtypes are related to more aggressive disease, to younger age at presentation, and IgA lambda proteins secretion.
- High-risk features include presence or deletion of p53, deletion of 1p, immunoglobulin heavy chain translocations t(4:14) or t(14:16).
- Patients with 17p deletion have progression-free survival of only 1 year and an overall survival of 18-24 months.
- Almost all patients have abnormal chromosomes by fluorescence in situ hybridization including translocations, deletions, and aneuploidy but with standard metaphase analysis only 18-30% have abnormal karyotypes and is explained by a low proliferative rate on multiple myeloma cells needed for conventional cytogenetics.
- Cytogenetic abnormalities in conventional studies indicate the presence of a high proliferative rate malignancy with poor prognosis.
- Patients with hyperdiploid karyotypes have a good prognosis with chemotherapy induction and high dose chemotherapy with bone marrow transplantation.
- Patients with the (4:14) or 17p gene deletion have a poor prognosis with most conventional therapy.
- Chromosome 13 abnormalities associated with unfavorable outcomes after conventional and stem cell transplant treatments.
- Aneuploidy occurs frequently with monosomies including chromosomes 13, 14, 16 and 22 more frequent than trisomies of 3, 5, 7, 9, 11, 15, 19 and 21.
- Hyperdiploid changes are associated with multiple trisomies and a low incidence of IgH translocations.
- Nonhyperdiploid lesions have a high prevalence of IgH translocations.
- In IgH translocations associated with 5 recurrent chromosomal partners including 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (fibroblast growth factor receptor 3), 16q23 and 20q11.
- CD138 immunostains utilized for quantification of myeloma.
- Any chromosomal abnormality is associated with worse prognosis.
- The CAR T-cells that have shown the most therapeutic promise are those targeting the CD19 protein, and the BCMA protein in multiple myeloma.
- Bortezomib therapy in patients with 13q deletion can produce durable responses indicating this drug can overcome the adverse effects of 13q del abnormalities.