Treatment With KRd Plus Autologous Stem Cell Transplant Elicits Durable Survival Benefit in Myeloma

Patients with multiple myeloma with standard or high-risk cytogenic abnormalities who were treated with carfilzomib, lenalidomide, and dexamethasone plus autologous stem cell transplant experienced promising responses.

A regimen consisting of carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) plus autologous stem cell transplant (ASCT) plus maintenance KR resulted in durable responses for patients with multiple myeloma with standard or high-risk cytogenic abnormalities, according to data from the FORTE trial (NCT02203643) that were presented at the 18th International Myeloma Workshop.

In addition, patients from both groups had improved progression-free survival (PFS) at 3 and 4 years.

“Despite the limitations due to a small number of patients, the benefit of KRd plus transplant over KRd continuous without transplant, and that of carfilzomib-lenalidomide versus lenalidomide alone as a maintenance was observed among all patient subgroups except those carrying amplification 1q,” investigator Roberto Mina, MD, of the European Myeloma Network in Italy said during a presentation on the findings.

The trial included 396 newly diagnosed patients with multiple myeloma who were transplant-eligible and younger than 65. Of the patients in this analysis, 243 had high-risk, 105 had double-hit, and 153 had standard risk disease.

They were randomized to receive KRd with ASCT (KRd-ASCT), carfilzomib plus cyclophosphamide and dexamethasone (KCd) with ASCT (KCd-ASCT), or KRd without ASCT (KRd12). After the second consolidation, they were again randomized to receive either KR or lenalidomide maintenance therapy.

The aim of the study was to evaluate the efficacy of different induction and consolidation strategies, as well as that of maintenance in terms of PFS and one-year minimal residual disease negativity rates according to patient cytogenetic risk.

“For this purpose, patients were stratified in three risk groups: standard risk if no chromosomal alteration was detected, high risk if at least one chromosomal alteration was detected, and double-hit myeloma in presence of at least two high-risk chromosomal abnormalities,” Mina said.

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

Among high-risk patients, KRd-ASCT improved PFS compared with KRd12 (HR 0.6; P = .04) and KCd-ASCT (HR, 0.57; = .01). There were 4-year PFS rates of 62%, 45%, and 45%, respectively.

In double-hit patients, KRd-ASCT improved PFS compared with KRd12 (HR, 0.53; P = .07) and KCd-ASCT (HR, 0.49; P = .03), with 4-year PFS rates of 55%, 31%, and 33%, respectively.

Similarly, with standard-risk patients, KRd-ASCT improved PFS when compared with KRd12 (HR, 0.47; P = .05) and KCd-ASCT (HR, 0.38; P = .01), with 4-year PFS rates of 80%, 67%, and 57%, respectively.

There was also a PFS benefit in patients with del17p, t(4;14), and 1q gain who received KRd-ASCT compared with KRd12. Patients with del1p saw greater benefit from KRd-ASCT and KRd12 than KCd-ASCT. Patients with amp1q had the worst outcomes regardless of which treatment type they received.

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

There was more benefit with KR maintenance in patients with del17p, t(4;14), 1q gain, and del1p. Patients with amp1q again had the worst outcome and did not receive any benefit from KR compared with R.

The results provide an effective option for high-risk patients, which is especially significant considering their clinical needs are currently unmet.

Reference

Mina R, Zamagni E, et al. Carfilzomib-Based Induction/Consolidation With or Without Autologous Transplant and Lenalidomide (R) or Carfilzomib-Lenalidomide (KR) Maintenance: Efficacy in High-Risk Patients of the FORTE study. Presented at: 18th International Myeloma Workshop; September 8-11, 2021; Vienna, Austria. Oral Abstract Session.