FORTE trial results: KRd with or without transplantation in newly diagnosed myeloma according to risk status

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Published: 6 Jun 2019
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Dr Francesca Gay - University Hospital City of Health and Science of Turin, Turin, Italy

Dr Francesca Gay talks to ecancer at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting about the results from the randomised FORTE trial which looked at the use of carfilzomib lenalidomide dexamethasone (KRd) with or without transplantation in newly diagnosed myeloma and evaluated according to risk status.

She reports that the rate of response and of minimal residual disease negativity between the two arms was similar but that patients with standard risk had a higher rate of stringent CR and minimal residual disease negativity.

Dr Gay adds that high risk patients receiving transplant had a higher rate of 1 year sustained minimal residual disease negativity than patients who did not.

She explains that this could be why patients who did not receive transplant have a higher rate of relapse compared with patients who received transplant.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

The abstract was about the FORTE study which is a randomised trial for newly diagnosed patients younger than 65 years and eligible for high dose chemotherapy and transplant. We analysed for this report the outcome of patients randomised to the KRd, transplant KRd, arm versus the patients randomised to KRd without transplant. KRd is a combination of carfilzomib, lenalidomide and dexamethasone and patients enrolled in the study can receive these as induction before transplant and consolidation after or the same treatment, the KRd, but for up to twelve cycles without transplant.

We saw that the rate of response and of minimal residual disease negativity between the two arms was similar, however, patients with standard risk had a slightly higher rate of stringent CR and minimal residual disease negativity. We looked at the outcome of high risk patients who received transplant or not and we saw that high risk patients receiving transplant have a higher rate of one year sustained minimal residual disease negativity compared to patients who did not. This is probably the reason why patients who did not receive transplant have a higher rate of early relapse compared with patients that received transplant.

So based on this we conclude that both regimens, KRd plus transplant and KRd without transplant, were effective. They can induce high quality responses, however, transplant is more effective in high risk than no transplant because it induced a high rate of sustained remission and reduced the rate of early relapse. We need a longer follow-up to evaluate the progression free survival and the overall survival data.

Adverse events that were reported in another previous publication were different in the two arms. With KRd without transplant we had a bit more dermatologic toxicity because you continue lenalidomide for a longer time period and a bit higher increase, a mild increase, in liver enzymes but reversible and a bit mild higher rate of hypertension. I think this is related to the long-term duration of the KRd. Of course patients that received transplant, on the other hand, had all the toxicity related to transplant which is the hematologic toxicity and the infection. That was, however, superimposable to other reports where patients received transplant.

In light of these results how do these results maybe guide a clinician’s decision to decide what treatment to use?

I think that transplant so far is the standard for most newly diagnosed patients, at least in Europe the standard approach is to perform an upfront transplant. This trial showed that in high risk patients this, of course, is still the best treatment option. I think we need a longer follow-up to see if for standard risk patients even the non-transplant option is enough. At present the results are similar but that could be because the follow-up is too short and we do not have yet events in PFS to show any difference.