Combination carfilzomib, lenalidomide, and dexamethasone (KRd) followed by autologous stem cell transplant (ASCT) proved more effective than other carfilzomib-based regimens in patients with newly diagnosed multiple myeloma, according to results of the phase 2 FORTE trial.

The trial also suggested that maintenance therapy with carfilzomib plus lenalidomide improved progression-free survival (PFS) compared with lenalidomide alone. These results were published in The Lancet Oncology.

The FORTE trial (ClinicalTrials.gov Identifier: NCT02203643) included 474 patients with newly diagnosed multiple myeloma who were eligible for transplant and 65 years of age or younger.


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Patients were randomly assigned to receive 1 of 3 treatment regimens:

  • KRd induction followed by melphalan-ASCT and KRd consolidation (158 patients)
  • 12 cycles of KRd (KRd12) only (157 patients)
  • Combination carfilzomib, cyclophosphamide, and dexamethasone (KCd) induction followed by melphalan-ASCT and KCd consolidation (159 patients).

At the end of consolidation, 356 patients were randomly assigned to maintenance with carfilzomib plus lenalidomide (178 patients) or lenalidomide alone (178 patients).

The median duration of follow-up was 50.9 months from the first randomization and 37.3 months from the second randomization.

Response and PFS

After induction, 70% of patients who received KRd and 53% of those who received KCd achieved a very good partial response or better (odds ratio [OR], 2.14; 95% CI, 1.44-3.19; P =.0002).

The 4-year PFS rate from the first randomization was 69% with KRd plus ASCT, 56% with KRd12, and 51% with KCd plus ASCT. The median PFS was not reached, 55.3 months, and 53 months, respectively.

There was a significant reduction in the risk of progression or death in the KRd-ASCT arm compared with the KCd-ASCT arm (hazard ratio [HR], 0.54; 95% CI, 0.38-0.78; P =.0008). There was no significant difference in PFS between the KRd12 and KCd-ASCT arms (HR, 0.88; 95% CI, 0.64-1.22; P =.45).

The 3-year PFS rate from the second randomization was 75% with carfilzomib-lenalidomide maintenance and 65% with lenalidomide alone (HR, 0.64; 95% CI, 0.44-0.94; P =.023).

Safety

During induction and consolidation, the most common grade 3-4 adverse events (AEs) in the 3 arms were:

  • Neutropenia — 13% in the KRd-ASCT arm, 10% in the KRd12 arm, and 11% in the KCd-ASCT arm
  • Dermatologic toxicity — 6%, 8%, and 1%, respectively
  • Hepatic toxicity — 8%, 8%, and 0%, respectively.

Treatment-related serious AEs occurred in 11% of patients in the KRd-ASCT arm, 19% in the KRd12 arm, and 11% in the KCd-ASCT arm. Pneumonia was the most common serious AE, occurring in 4%, 3%, and 3% of patients, respectively.

There were 2 treatment-emergent deaths in the KRd-ASCT arm, 2 in the KRd12 arm, and 3 in the KCd-ASCT arm.

During maintenance, the most common grade 3-4 AEs were neutropenia (20% in the carfilzomib-lenalidomide arm and 23% in the lenalidomide-alone arm), infections (5% and 7%, respectively), and vascular events (7% and 1%, respectively). There was 1 treatment-emergent death in the carfilzomib-lenalidomide arm.

“Our data show that KRd plus ASCT showed superiority in terms of improved responses compared with the other two treatment approaches and support the prospective randomized evaluation of KRd plus ASCT versus standards of care (eg, daratumumab plus bortezomib plus thalidomide plus dexamethasone plus ASCT) in transplant-eligible patients with multiple myeloma,” the researchers concluded.

Disclosures: This research was supported by Amgen and Celgene/Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Gay F, Musto P, Rota-Scalabrini D, et al. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): A randomised, open-label, phase 2 trial. Lancet Oncol. Published online November 11, 2021. doi:https://doi.org/10.1016/S1470-2045(21)00535-0