1/ Risk stratification: This is important both for counseling patients and to decide on treatment options. The more high risk factors, the higher the risk.
2/ Initial therapy. The 3 main choices are VRd, DRd, and Dara-VRd.
I prefer VRd. But the other options are reasonable. Transplant eligible patients need 3-4 cycles, then stem cell collection.
3/ Initial Therapy. For patients not eligible for transplant, results with DRd are outstanding. But it is more expensive and requires prolonged use of a triplet.
4/ Future of Initial Therapy: Many trials are evaluating 3 vs 4 drugs.
Quadruplets may come out on top. But are they needed for everyone? Or can patients MRD- after a triplet do just as well without the 4th drug. This is what we are trying to answer in our current RCT @mtmdphd
5/ Transplant: Auto Transplant is still important. It's role is not in debate. Only the timing. In standard risk patients less than 65-70, early or delayed may be OK. Patient choice matters. Also prefer early transplant in high risk MM.
OS of early vs delayed at 8 years is same.
6/ Maintenance: Lenalidomide for standard risk; Lenalidomide plus Bortezomib for high risk is the current preferred approach.
Our current US cooperative group phase IIIs are looking at adding Dara, or MRD directed escalation or de-escalation.
7/ First Relapse. Thankfully with today's treatment first relapse occurs about 4 years following initial therapy. This will get longer with time.
When relapse occurs a number of options are available. Choice depends on what the patient is refractory to. My approach is below.
8/ Second or higher relapse. Thankfully the first relapse regimen can usually work for a long time. This is also improving.
There are a number of treatment options available for second or higher relapses.
9/ Immunotherapy provides great promise: especially CAR-T and bispecifics. One CAR-T is already approved (ide-cel). One more maybe in a month (cilta-cel).
A number of bispecifics are showing high activity. And unlike CAR-T are "off the shelf". But none are approved yet.
10/ In the future we may pick immunotherapy based on the target antigen. We will face the situation of myeloma refractory to BCMA targeted approaches. So I'm glad Talquetamab and Cevostamab target something besides BCMA.
Link to thread from yesterday on How we treat smoldering multiple myeloma. @SagarLonialMD@mvmateos
Risk stratification is based on the Mayo 20-2-20 system.
High risk is any 2 factors abnormal. These patients had 90% reduction in risk of end organ damage in the two RCTs of Len/Rd vs Observation. nature.com/articles/s4140…
China, New Zealand, Hong Kong, Taiwan, South Korea, Singapore, Japan, Australia, et al.
How did they do it? Did they have better experts or expertise? Did they implement preventive measures faster? Was the population more receptive. All of the above? More?
Need in depth study. And with humility and attention to detail.
So we learn and don't repeat mistakes. Perhaps nothing is fixable. But it's worth knowing what the reasons are.
Most of them kept deaths low by keeping cases low. Even when cases climbed with omicron it was in a vaccinated population. So they had accomplished what they needed to accomplish.
That means it's not a question of obesity rates or diabetes or age distribution.
The study used data from 1327 patients to develop the risk stratification model. The model was then validated in 502 patients enrolled in the MMRF CoMMpass study.
Stage migration from RISS and ISS shown below.
There are a lot of risk stratification models. We focus the widest applicability worldwide using markers that are clinically available in most places.
The risk stratification and hazard ratios are valuable for counseling.
Having spoken to many experts and organizations including experts from Costco and @AARP it was clear that even if the intent is there, providing low cost drugs in our system is extraordinarily difficult.
So I'm glad someone is taking the initiative.
The fact that your copay with insurance can be higher than paying out of pocket at the pharmacy tells you how broken the system is, how much the entire supply chain except the patient benefits from the current system.
One thing that's clear watching the pandemic for the last 2 years is that the only way to truly contain it was early action. A few countries did it the right way. Saved a lot of lives.
If you didn't do the right thing early on, the task became infinitely harder.
Countries which successfully contained covid early on now face a problem of how long they can realistically sustain their approach.
These countries have vaccinated their public and did all the right things. But Omicron makes it very hard.
Countries which acted late find rising cases the moment preventive measures are relaxed. And whenever a new variant arises. It's disheartening.