Shaji Kumar, M.D.
The way that newly diagnosed patients with multiple myeloma is treated has changed significantly over recent years, especially as new drugs moved into the treatment realm for the disease, says Shaji K. Kumar, M.D.
"There are a lot of changes coming into myeloma," he says. "Clearly, there are new therapies that can control the disease once it manifests itself, but I think what is exciting is the ability to intervene early in some of these patients, before they even get myeloma."
Kumar, professor of Medicine, Mayo Clinic, discussed proper diagnosis, risk stratification and personalized medicine for patients with multiple myeloma during an interview with CURE
the National Comprehensive Cancer Network (NCCN) 12th Annual Congress on Hematologic Malignancies.
What has prompted this discussion of management in the newly-diagnosed population?
I think multiple things have changed in myeloma starting with diagnosis and risk stratification, as well as use of various drugs. In terms of diagnosis, the new diagnostic criteria came out a couple years ago, which incorporated patients with soldering myeloma who also had some biomarkers of early progression. These patients are now being considered as patients with myeloma. So, it is important to make the right diagnosis, especially when determining when to start treatment for these patients.
The second important aspect is the risk-stratification. We have used FISH risk-based stratification for quite some time. There is also the revised International Staging System (ISS) staging system, which incorporates both FISH and ISS as well as serum lactate dehydrogenase (LDH), to give a better sense of patients who are not going to do well or patients who are going to do relatively well compared to the other patients.
The risk stratification is very important because it may have some implications as to what regimen you might use and what combinations or sequence of drugs you may use and for how long.
Finally, unfamiliarity with using combinations usually deters people in the community from using these multi-drug combinations. We know from the phase 3 trial that combining Velcade (bortezomib) with Revlimid (lenalidomide) and dexamethasone clearly improves survival for these patients, and should be considered as the standard of care unless there is a compelling reason that they cannot get one of those drugs.
Of course, patients should always be considered for clinical trials because we should always be improving upon treatments. Being able to use the newer drugs in combinations is going to be key for the future.
What are some key messages you'd give about treating newly diagnosed patients with myeloma?
The key messages would be to make the correct diagnosis, making sure the patients get their FISH testing and their risk stratified appropriately, and then making sure they get a combination of a proteome inhibitor and immunomodulatory drugs.
Other aspects of care of myeloma treatments that I think everyone needs to keep in mind is the management of the complications of the disease, and side effects of therapy. Many of these patients with myeloma come in with comorbidities—keep in mind the median age of these patients is 67, so they tend to be frail. Myeloma itself can significantly impair the performance status of these patients, and some patients may present with renal insufficiency or significant anemia, which can exacerbate the preexisting cardiac problems. All of these need to be factored in when you are deciding on treatment. For patients who are in good shape and are transplant eligible, the three-drug combination is the standard of care. But, if patients have any comorbidities or are frail, we really need to consider dose-modifications of this triplet regimen—maybe only using one drug instead of the triplet. Understanding the disease risk, but also understanding the host, is very important in terms of making the decision of initial therapy.
The second thing to consider is transplant eligibility. Obviously, somebody who is young is typically transplant-eligible, and the age cutoff varies from country to country. In the United States, we transplant patients up to 75 commonly. But you must look at each patient in their own context. Someone could be young with a lot of comorbidities, or someone could be older and very fit — age alone cannot be the criteria for selecting somebody for transplant. Now, the second part of transplant eligibility is that today, the patient may look ineligible because of the pain from the bone lesions — their performance status is poor. But, after one or two cycles of therapy, their performance status could be much better and could be reconsidered. I don't think we should shut the door on transplant ineligibility based on that initial visit.
The final point that people need to keep in mind is the management of the side effects from these drugs. Now, obviously, all of these drugs have toxicities, and when you use them in combination, you can see even more toxicities. It is very important to manage the toxicities appropriately, instead of rapidly decreasing the dose, because suboptimal doses of these drugs can be more harmful in the long run. There are a lot of good guidelines that have come out on how to modify drugs based on toxicities, and how to change the doses based on the initial assessment of frailty.
Looking ahead, how do you see the adoption of good early management techniques affecting the landscape of multiple myeloma?
In the best-case scenario, if people are doing all these steps and all patients get the optimal initial therapy, I think two things are going to happen. Duration of first remission is going to get longer and longer. Right now, we know that duration of remission is roughly four years in the patients who get transplant and maintenance, and in patients who are transplant ineligible, it is somewhere between two and three years, based on the current approaches.
Now, in addition to patients saying in remission longer, they are going to come into the first relapse in much better shape than they do today. In essence, what could happen is that patients who are experiencing their first relapse of myeloma could be in as good or better shape as the patients with newly-diagnosed myeloma that we see today. That opens up the option to use a more intense therapy in the second line, which could lead to a more prolonged disease response in the relapsed setting. I think each of those building blocks become bigger and bigger as more effective therapies are used upfront.