ASCO 2019 | Risk subgroup analysis from the FORTE trial

On Sunday 02 June, 2019, Francesca Gay, University of Torino, Torino, IT, presented an updated risk analysis from the FORTE trial (NCT02203643) during the American Society of Clinical Oncology (ASCO) annual meeting. This analysis compared carfilzomib (K), lenalidomide (R) and dexamethasone (d) (KRd) induction, followed by high-dose melphalan (HDM) plus autologous stem cell transplant (ASCT) and KRd maintenance, to KRd alone in patients with newly diagnosed multiple myeloma (NDMM).

Study design and background

The design of the FORTE trial, in transplant eligible patients with NDMM ≤65 years is shown in Table 1 with patients randomized 1:1:1 to one of the three arms. The dosing of the drugs was as below;

• K: 36 mg/m² on days 1–2, 8–9 and 15–16
• Cyclophosphamide(C): 300 mg/m² on days 1, 8 and 15
• R: 25 mg on days 1–21
• d: 20 mg on days 1–2, 8–9, 15–16 and 22–23

A second randomization (1:1) was then conducted to either lenalidomide or carfilzomib and lenalidomide maintenance. The pre-maintenance response rates for the intention-to-treat (ITT) population are shown in Table 2.

Table 1: Trial design

Table 2: Pre-maintenance analysis in the ITT population

Updated risk analysis

• For the purposes of this risk analysis, KRd_ASCT was compared to KRd12 
• Evaluations were conducted in patients with standard- and high-risk disease
• Aims:
  • Evaluate the pre-maintenance response rates of sCR, ≥CR and ≥VGPR, and MRD negativity as well as 1-year persistent MRD negativity
  • Evaluate rate of early relapse (≤18 months from first randomization)
• Median follow-up: 25 months

The subgroup analysis results are shown below in Tables 3–6.

Table 3: Patient characteristics of note

Table 4: Pre-maintenance response rate, by R-ISS stage of disease

Table 5: Early relapse rate (≤18 months) after first randomization

Table 6: Factors associated with early relapse using a multivariate logistic regression model

Conclusion

Both KRd_ASCT and KRd12 induced high quality responses in this study, with good MRD negativity rates, which were higher in the KRd_ASCT arm. The risk of early relapse was reduced in high-risk patients who underwent ASCT, showing a benefit of ASCT in this population. Longer term follow-up is required to evaluate both progression-free survival and overall survival.