Efficacy and safety of KRd or KCd induction in multiple myeloma

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Published: 13 Dec 2018
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Dr Francesca Gay - University of Torino, Torino, Italy

Dr Francesca Gay speaks to ecancer at ASH 2018 about the Forte trial into the efficacy and safety of KRd or KCd induction in multiple myeloma.

She explains that the three arms of the study were KRd induction-ASCT-KRd consolidation vs KCd induction-ASCT-KCd consolidation vs 12 cycles of KRd.

Dr Gay reports that both the KRd transplant treatments and extended therapy significantly improved the response rate in comparison with treatment with KCd and 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 Forte study is a randomised study that enrolled about 470 patients in Italy, patients with newly diagnosed myeloma and eligible for transplant. They were randomised to receive an induction with a carfilzomib-based regimen; in one arm they received carfilzomib, cyclophosphamide dexamethasone induction followed by transplant and then by carfilzomib, cyclophosphamide and dexamethasone consolidation. In the second arm patients received treatment with carfilzomib, lenalidomide dexamethasone induction followed by transplant and then four cycles of carfilzomib, lenalidomide, dexamethasone consolidation while patients randomised in the third arm of the study received treatment with carfilzomib, lenalidomide, dexamethasone for a total of twelve cycles with no transplant, so a sort of KRd extended therapy.

We saw that treatment with both KRd transplant and KRd extended therapy significantly improved the rate of response compared with treatment with KCd and transplant and this was true for the rate of at least very good partial response that was about 90% at the end of this treatment in the two KRd arms. The rate of stringent CR was also significantly higher in the two KRd arms compared with the KCd – about 44% of patients achieved stringent CR in the two arms. More importantly, also the rate of minimal residual disease negativity in the two KRd arms was comparable – 58% of patients – and was comparable between the two arms and was significantly superior compared with KCd.

We also saw that the treatment was well tolerated with less than 10 percent of patients who had discontinued treatment for toxicity. Also the toxicities were non-haematological toxicities, higher in the two carfilzomib, lenalidomide, dexamethasone arms compared with the carfilzomib, cyclophosphamide arm, however manageable and mainly represented by an increase in liver enzymes, cutaneous dermatological toxicity or by hypertension while haematological toxicity was comparable.
This trial showed that the two KRd treatments, with transplant and without transplant, are able to induce a similar rate of VGPR, stringent CR and minimal residual disease negativity in patients with newly diagnosed myeloma and that the treatment is very well tolerated and is manageable. Of course, the follow up of this study is still short and we need a longer follow up to evaluate the effect of these regimens over progression free and overall survival.