Dear Colleagues,
My Dad (66 years old) has recently beed recently diagnosed with multiple myeloma. Apart from significantly elevated monoclonal protein, he has no symptoms. He has had his blood protein levels high for the past 5 years. Detailed medical exams showed that his bones, kidneys, and blood work (other than what I have already mentioned) are all fine. My Dad has always been fit and he is still feeling well overall.
He has an opportunity to join a clinical study that uses daratumumab combined with standard treatment for multiple myeloma. My understanding is that the treatment he would get is considered chemotherapy.
Is undergoing the chemotherapy the right thing to do now, considering multiple side effects of it (with or without daratumumab)? Or should he wait until symptoms begin to appear. My Dad’s doctors do not seem to share the same opinion on this matter.
I would deeply appreciate suggestions. Please note that I am a neurolignuist, not an MD. Therefore, I may have worded something incorrectly here. However, I will gladly clarify or provide more detailed information if helpful.
Thank you very much in advance,
Monika
Dear Monika,
The exact diagnosis of your father is probably smoldering multiple myeloma (SMM), according to the information you gave about his medical data. SMM is defined as following criteria:
Serum monoclonal protein: IgG or IgA ≥3 g/dL, or
Bence Jones protein ≥500 mg/24 h and/or
Clonal bone marrow plasma cells between 10% and 60% and
Absence of myeloma-defining events or amyloidosis.
The risk of progression to symptomatic multiple myeloma of SMM is about 10% annually.
Experts in hematology consider SMM as an excellent setting to test the efficacy of novel theurepatic drugs such as ixazomib, pomalidomide, elotuzumab, and daratumumab in myeloma treatment.
Despite standard care of SMM is close clinical observation until development of symptoms, International Myeloma Working Group recommends therapy for SMM cases at high risk (about 50% risk for progression to symptomatic multiple myeloma).
For more information please visit:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432003/
To treat patients with active myeloma, they must have CRAB (hypercalcemia, renal lesion, anemia and/or bone lesion >=1) or 60% or higher clonal plasma cells on bone marrow examination or serum involved / uninvolved free light chain ratio of 100 or higher, provided the absolute level of the involved light chain is at least 100mg/L (a patient's involved free light chain either kappa or lambda is the one that is above the normal reference range; the uninvolved free light chain is the one that is typically in, or below, the normal range). However, if your father has MGUS or smoldering myeloma, he can participate in clinical trial with various kinds of drugs, available, but It is a voluntary choice, he will not be obligated to do that if he does not have the sign or symptoms of the disease, therefore, he could only observe closely, because he has a risk of transformation to MM. Best regard! Ademar.
I agree with Ademar's statement, that in order to be treated, your father should have symptomatic myeloma (CRAB) or myeloma with the above mentioned expanded criteria of IMWG defined by >60% clonal plasma cells and FLC ratio >100 (involved/univolved), and here I would add that he should undergo skeletal imaging with spine MRI or low-dose whole body CT scan and if >1 bone lesions of at least 5mm are found, then this constitutes another myeloma-defining event (MDEs). Treatment is not necessarily any more with chemotherapy but rather with non-chemo drugs, such as Proteasome inhibitors (PIs); bortezomib, carfilzomib, ixazomib, Immunomodulatory drugs (IMiDs); thalidomide (its use is currently discouraged due to more severe side-effects comparably to other IMiDs), lenalidomide (Revlimid), Pomalidomide, and finally steroids, preferably dexamethasone. A very popular and effective combination is VRD which stands for Velcade (bortezomib)-Lenalidomide (Revlimid)-Dexamethasone producing response rates >90-95% of patients. Moreover, if the patient is what we call "transplant-eligible", i.e. able to tolerate high-dose chemotherapy with Melphalan followed by an autologous hematopoietic stem cell transplant (ASCT), he should have hematopoietic stem cells (CD34+) harvested after 3-4 cycles of VRD and then given after high-dose Melphalan. Your father is at an age that I think must be transplant-eligible, provided that he has no other significant comorbidities.
If your father has an asymptomatic myeloma, i.e smoldering myeloma (SMM), then he should be observed closely for signs of active myeloma, or treated according to protocols applied for SMM, and such an exmple is the combination of Lenalidomide-Dexamethasone (LenDex)..!
I hope that these help...!!! Good luck !!!
Dear Gulali Aktas , Ademar Dantas da Cunha Junior and Christos Kosmas ,
A big thank you to each of you for the most helpful information.
My father now has all the required test results. We sill do not know whether my father should join the clinical study (daratumumab vs. standard clinical treatment for multiple myeloma). My father's doctors continue to have have opposing opinions and I would be grateful for your suggestions and comments.
I am listing his recent results below.
clonal plasma cells: 2%
MRI skeletal imaging with spine: no lesions of at least 5mm
CRAB – all fine
GAMMOPATHY:
Immunoglobulin A: g/l
That haemoglobin is not a good sign, and there's significant immunoparesis (quite low IgA & IgM) due to the paraprotein. I didn't see BMAT plasma cell number there, or is it 2% on morphology or is that on flow cytometry? So the A of CRAB is not fine, & is an indication for therapy if it's myeloma related. But the best thing is for your father to discuss with his doctor (you may go with him if he's comfortable) & understand the oncologist's view. There's more to patient care/therapy than the textbook stuff & lab results, especially if the doctor has been monitoring your dad for some time. Good luck
Dear Moses Chatambudza ,
The 2% result was for clonal plasma cells on a bone marrow examination. Is this the BMAT measure you asked for?
Sorry, this is not my field and all the test results my Dad has had are not in English.
Dad has consulted a few doctors and some say to go ahead with the treatment and some say to wait. I guess his case is not this straightforward...
I will be grateful for any further suggestions you may have.
Thank you so much,
Monika
So, according to the lab results, your father has an IgGλ MGUS, as no CRAB + MDE are met - Anemia with Hct=39.3% - please note at this point that Hb is in mmol/L and therefore there is no chance with this Hct=39.3 and MCV-MCH to have a Hb
Dear Christos Kosmas ,
Thank you very much for going though the results. I am attaching some more below. Do the additional results change anything, or would you still say this is an IgGλ MGUS?
TREPANOBIOPSY:
Rich cell marrow (?) with all lines represented. Presence of single plasma cells. No fibrosis.
CD34+ - appr. 50-60%, kappa
Obviously, there is a small (2%) clone of λ-LC expressing plasma cells (monoclonal suggested by λ-LC clonal excess by IHC) that do not carry high-risk clonal cytogenetic abnormalities or translocations, i.e. t(4;14), t(14;16), del13/13q, 1q(+), or del1p.
Therefore, with the results of the workup provided, this is an MGUS.
Hi. I{m not an expert in smoldering multiple myeloma, but there is a world clinical trial using just daratumumab.
The hypothesis is tahat using that drug, the symptoms never appears, or it does at a long time.
Cite
Christos Kosmas
Metaxa Cancer Hospital
I' m sorry for my recommendation for being an MGUS (I was misguided by the low clonal plasma cell %), but according to the lab results your father has SMM that is likely high-risk according to the refined Mayo Clinic/Spanish Myeloma Group criteria; BMPCs>10%, FLCr>20, M-protein>2gr/dl. Your father has 2 of the above criteria: FLC (λ/κ)=86:1 and M-protein=3.47 g/dl (>3.0g/dl), which place him to the high-risk subgroup having a median TTP of 29 months [Blood Cancer J. 2018 Jun; 8(6): 59; doi: 10.1038/s41408-018-0077-4].
Therefore, he may need treatment with Len/Dex or more aggressively with KRd x 6 --> autotransplant (high-dose Melphalan) --> KRd x 2 consolidation --> Len maintenance, or more recently Daratumumab montherapy.
Cite
2 Recommendations
Mehmet Rami Helvaci
The Marmara University (1991)
Never before signs or symptoms.
Cite
Christos Kosmas
Metaxa Cancer Hospital
Dr. Mehmet Rami Helvaci:
According to the expanded IMWG criteria, diagnosis of MM does not require to have symptoms, i.e. a FLC ratio >100:1 or BMPCs>60% may have no associated symptoms, but this is MM (previously SMM) and requires treatment...! It is like you would say to the patient that you have asymptomatic MM but in the ensuing 2 years, with observation-without treatment, you have >80% chance of developing for example bone fractures, hypercalcemia, and renal failure...!!! Now in the setting of SMM, high-risk features predict for a rapid development of symptomatic MM and according to most experts requires treatment, but treatment type and drugs are currently under investigation. A rather "standard" regimen is Len/Dex, that has demonstrated prolongation of time to MM development...!
Cite
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