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Navigating the Complex Treatment Landscape of Multiple Myeloma in Transplant Eligible Patients
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Current Standards of Transplant Eligibility for Patients With Multiple Myeloma
December 19, 2019
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January 17, 2020

Current Standards of Transplant Eligibility for Patients With Multiple Myeloma

Ajai Chari, MD, discusses transplant eligibility for patients with multiple myeloma.

Ajai Chari, MD: The criteria for transplant eligibility in myeloma is primarily organ function. So, ejection fraction greater than 50% pulmonary function tests. So, in particular, FEV1, DLCO greater than 50%, good performance status–those are the main things. We often talk about age, but nothing in human beings is binary. I think most US centers have an estimate of around 70, but we could all imagine that there could be a very sick 50-year-old with multiple comorbidities and a 73-year-old. I think the only other thing I would add is that in the above 70 patient population, I don't think the decision has to be made at initial diagnosis. We can see how they respond and tolerate therapy, and if somebody has difficulty tolerating treatment or they don't get into a deep remission, they may very well benefit from a transplant; but those who are doing beautifully on standard chemo may not need transplant consolidation.

In terms of the proportion of patients with myeloma who are transplant eligible, we say that the median age of myeloma is in the late 60s or 70, which would mean that approximately at least 50% of patients would be eligible. Unfortunately, we know that very few patients are getting referred for transplant consideration. So, I think it's important to at least have that initial consultation. The other thing I would just add is in the era of CAR-T, it's also important to have that discussion because after CAR-T, which is very promising, a lot of patients are ending up with low blood counts, and it's nice to have some stem cells on hold or reserve as an insurance policy to help with the marrow resuscitation.

The NCCN recommendations for induction therapy with transplant eligibility consideration is essentially based on the SWOG S0777 study, which compared VRD to RVD and showed that the triplet VRD, which is bortezomib lenalidomide index, resulted in superior response rate, PFS [progression-free survival], and OS [overall survival], although that was actually for a group of patients without the intent to transplant. So, we extrapolate from that because historically we've been using in the US RVD as our default triplet induction regimen for the last decade, and well before SWOG was resulted, but at least it substantiates triplet. So, I think most patients are getting at least that regimen, but in the OPI IMiD Dex [dexamethasone], there's also some data for carfilzomib lenalidomide index. I think that's particularly worth considering in patients who may have neuropathy, are young, no cardiac issues, and are very fit–it's a very potent drug. High risk disease may also be a consideration, and so I think those have been the primary induction regimens.

There's some patients who benefit from an induction therapy of a cycle with cyclophosphamide, so a PI cyclophosphamide index, but 2 studies have shown that I think the OPI IMiD Dex are superior–that's the IFM study which compared bortezomib Thal-Dex to bortezomib cyclophosphamide Dex and show that the thalidomide was superior. Also, in the FORTE study, KRD, carfilzomib lenalidomide Dex, was compared to carfilzomib cyclophosphamide Dex (KCd), and also showed superiority with the image. So, I think generally we use the ImiD, but in a newly diagnosed patient perhaps who’s admitted in the hospital who has renal dysfunction, it's going to take some time to order the Revlimid, or lenalidomide, and in that setting, there may be a role for 1 cycle of a triplet with the cyclophosphamide.

For transplant eligible patients, the sequencing would essentially consist of this PI IMiD Dex triplet, followed by transplant, and we can discuss more because that's a discussion in of itself at the timing of transplant, but assuming somebody went to transplant and then went on to lenalidomide maintenance, which has been shown based on meta-analysis, as well as, individual studies to extend not only PFS but also in meta analyses OS. So, what that leaves us with is the vast majority of US patients who are transplant eligible end up becoming Len-refractory. So, I think that is a big issue because in the first relapse we have multiple studies that are showing improvement with the novel therapies compared to control arms and you can broadly define them, and divide them, into lenalidomide containing regimens and bortezomib containing regimens.

So, the lenalidomide backbone regimens, for example, would be the addition of either daratumumab, ixazomib, elotuzumab, or carfilzomib, and those are all phase 3 studies; but this patient that we took to transplant and had Len maintenance wouldn't be eligible for any of those. So, I think that is an important sequence in consideration. These patients would be eligible for all the bortezomib backbone studies. So, 1 could certainly pick from any of those, and examples of those might be pomalidomide bortezomib Dex, daratumumab bortezomib Dex, recently daratumumab with carfilzomib Dex–so those are options that we could use in a Len-refractory patient.
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