KRd-ASCT improves long-term PFS in multiple myeloma


Promising survival results were shown in the FORTE trial of carfilzomib plus lenalidomide and dexamethasone induction / consolidation with autologous stem cell transplant and maintenance with carfilzomib-lenalidomide in patients with multiple myeloma.

Significantly prolonged progression-free survival (PFS) rates were observed for induction / consolidation of carfilzomib (Kyprolis) -lenalidomide (Revlimid) -dexamethasone with autologous stem cell transplant (KRd-ASCT) and maintenance with carfilzomib-lenalidomide ( KR) compared to KRd without ASCT (KRd12) and lenalidomide (R), respectively, in patients with multiple myeloma who had standard or high-risk cytogenic abnormalities.

Data from the FORTE trial (NCT02203643) were presented at the 18th International Myeloma Workshop by investigator Roberto Mina, MD, Assistant Professor, Division of Hematology, Department of Molecular Biotechnologies and Health Sciences, University of Turin, Italy, and member of the medical committee of the surveillance team of the European Myeloma Network in Turin.

“Despite the limitations due to the small number of patients, the advantages of KRd plus transplant over continuous KRd without transplant and those of carfilzomib-lenalidomide over lenalidomide alone as maintenance were observed among all subgroups. of patients, with the exception of those carrying the 1q amplification, “Mina said. during its presentation.

The trial included 396 patients who had been newly diagnosed with multiple myeloma, were eligible for a transplant, and were under 65 years of age. Of the patients in this analysis, 243 were considered high risk, 105 were considered double hit, and 153 were considered standard risk.

“To this end, patients were stratified into 3 risk groups: standard risk if no chromosome alteration was detected, high risk if at least 1 chromosomal alteration was detected and double myeloma in the presence of at least 2 abnormalities. high-risk chromosomes, ”Mina mentioned.

They were randomized to receive KRd-ASCT, carfilzomib-cyclophosphamide-dexamethasone (KCd) plus ASCT (KCd-ASCT) or KRd without ASCT (KRd12). After the second union, they were again randomized to receive either KR or R (FIGURE).

In the overall patient population, the KRd-ASCT arm had significantly prolonged progression-free survival compared to the KRd12 and KCd-ASCT arms. KR maintenance also had a significantly prolonged PFS compared to R maintenance.

Among high-risk patients, KRd-ASCT improved PFS compared to KRd12 (HR: 0.6; P = 0.04) and KCd-ASCT (HR, 0.57; P = .01), with a 4-year PFS of 62%, 45% and 45%, respectively.

In double impact patients, KRd-ASCT improved PFS compared to KRd12 (HR: 0.53; P = 0.07) and KCd-ASCT (HR, 0.49; P = 0.03), with a 4-year PFS of 55%, 31% and 33%, respectively.

Likewise, in standard risk patients, KRd-ASCT improved PFS compared to KRd12 (HR: 0.47; P = 0.05) and KCd-ASCT (HR: 0.38; P = .01), with 4-year PFS rates of 80%, 67% and 57%, respectively.

Regarding chromosomal abnormalities, there was a benefit of PFS in patients with del17p, t (4; 14) and 1q gain when receiving KRd-ASCT compared to KRd12. Patients with del1p saw greater benefit from KRd-ASCT and vKRd12 than from KCd-ASCT. Patients with amp1qv had the worst results regardless of the type of treatment they received.

KR improved PFS in all 3 groups compared to lenalidomide, with 3-year PFS survival rates of 90% vs. 73% in standard-risk patients, 69% vs. 56% in high-risk patients, and 67% versus 42% in dual risk patients. hit patients.

There was more benefit with maintaining KR in patients with del17p, t (4; 14), gain 1q, and del1p. Patients with amp1q again had the worst outcome and received no benefit from KR over R.

The results provide an effective option for high-risk patients, which is particularly important given that their clinical needs are currently unmet.


1. Mina R, Zamagni E, Fazio F, et al. Carfilzomib-based induction / consolidation with or without autograft and maintenance lenalidomide (R) or carfilzomib-lenalidomide (KR): efficacy in high-risk patients in the FORTE study. Presented at: 18th International Workshop on Myeloma; from September 8 to 11, 2021; Vienna, Austria.

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