At Mayo Clinic, we classify myeloma patients into one of 6 non-overlapping categories based on primary cytogenetic abnormalities that occur at the MGUS stage. #MedTwitter
Needs testing beyond just looking for prognostic markers 1/
Because primary cytogenetic abnormalities occur at the time of origin of MGUS, even if testing was not done at baseline, we can classify myeloma based on a subsequent study.
Thus, a t(4;14) first detected in relapsed myeloma implies presence from the very outset at MGUS stage.
In contrast, secondary cytogenetic abnormalities such as gain 1q, del 17p, del 13, can occur at any time in disease evolution. Further one or more of these secondary abnormalities can occur in each of the 6 main types of myeloma & change their clinical course @NatRevClinOncol 3/
Thus a t4;14 myeloma can develop a del 17p. So can a t11;14 myeloma.
But t4;14 and t11;14 are mutually exclusive.
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The 6 primary types of myeloma differ some in clinical features, response to therapy, & prognosis. t4;14 myeloma is as much different from t11;14 myeloma as CLL is from mantle cell lymphoma.
Right now we consider all of them as one disease, but it’s an over simplification
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The future of myeloma will involve identifying optimal ways to manage not just these distinct entities, but go even beyond that. Such as managing t4;14 myeloma with del 17p differently than t4;14 myeloma without del 17p.
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As we learn more about the complex genetics of myeloma, in the future we may approach for instance t4;14 with a certain mutation pattern differently that t4;14 with a different mutation signature.
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Note: Presence of a cytogenetic abnormality from a clinical prognosis standpoint has a different implication depending on when it was detected. The effect of an abnormality on MGUS to MM progression is different than impact on MM prognosis @BloodCancerJnlnature.com/articles/bcj20…
The primary cytogenetic abnormalities are disease classifying as well as disease modifying. The secondary abnormalities are disease modifying, and the way and extent to which they modify will depend on the underlying primary cytogenetic type.
There more than 6 primary types of myeloma. But those 6 will comprise almost 90% of myeloma. The rest have IgH translocations involving a partner besides the 5 recurrent ones, or sometimes IgL translocations, etc
Failure to detect one of the 6 types is usually due to inadequate probes to look for them or low number of clonal cells in the marrow sample. Less often due to a primary abnormality besides the 6 main ones.
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FDA approval doesn’t necessarily mean standard of care.
Thread.
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For example FDA approved Dara VMP for frontline therapy in myeloma in 2018.
Literally no one used the regimen in the US.
Literally no one felt the regimen was standard of care in the US.
Before or after approval!
Why?
FDA adjudicates a sponsors submission on whether a given drug/regimen has met the burden of proving safety and efficacy.
Standard of care in clinical practice is a different standard: judgment of risk/benefit of available alternatives, and assessment of trial design/end points.
Cure is a simple word. But there is confusion when it comes to cancer. What cure is in cancer, and what we should aspire for?
When can we say that a given type of cancer is curable?
Thread
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There is a difference between when we can say a particular cancer is a curable type versus whether individual patients with a given cancer can be considered potentially cured.
They are not the same.
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To call a cancer curable we must be able to treat the cancer for a finite duration, stop all therapy, and know that a certain % of patients will never relapse
Early stage solid tumors, Hodgkin lymphoma, DLBCL, ALL, AML are curable. Real cure. The definition of curable cancer
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The 4 big myeloma randomized trials to watch out for @ASCO #ASCO24
1. Isa-VRd vs Isa-Rd newly diagnosed
2.Isa-VRd vs VRd (IMROZ)
3.DREAMM8 Bela-Pd vs Pd
4.Ven Dex vs Pom Dex (Canova)
See thread for why they are important.
1) The Triplet vs Quad trials with will define role of quads in elderly patients with newly diagnosed myeloma. They also provide frontline phase III data with Isatuximab— and a choice between Dara and Isa. For some patients Isa will be more cost effective. @Myeloma_Doc #ASCO24
2) Belantamab will make a comeback.
Corneal toxicity is low with reduced frequency dosing. The drug works very well. And in many patients with refractory myeloma belantamab may be safer and easier to do than bispecifics. We need options. #ASCO24
2/ Even though CART (cilta-cel) is approved for first relapse we are NOT including it in our main algorithm. Reserved only for special circumstances in this population. We have a long track record with standard triplets, and we are concerned about CART side effects.
3/ The current approach for second or higher relapse continues to define 3 specific types of Triple Class refractory. This makes it easier for clinicians to consider options.
To my followers who wonder what MOC is, and why many doctors are tweeting about it. Thread.
1) Maintenance of Certification (MOC) is a redundant requirement thrust on US physicians by a private organization. We resent it.
2) MOC is causing frustration and burnout. Over the years, ABIM certification and MOC have become entrenched and institutions and insurers require it and will not accept any other alternative.
I am advocating on behalf of my colleagues in the US for change. To end MOC.
3) MOC requires us to pay fees imposed on us by a private organization and take multiple choice question tests irrelevant to our practice.