The following article features coverage from the American Society of Clinical Oncology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

According to a recent analysis of results from the FORTE study (ClinicalTrials.gov Identifier: NCT02203643), assessment of disease risk is critically important in decision making regarding use of autologous stem cell transplantation (ASCT) as part of first-line therapy with carfilzomib/lenalidomide/dexamethasone (KRd) for younger (ie, <65 years) patients with multiple myeloma. The findings from this study were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.1

Previously reported results from the open-label, randomized, phase 2 FORTE trial, which enrolled adult patients with transplant-eligible, newly diagnosed multiple myeloma who were younger than 65 years, showed that rates of minimal residual disease negativity (MRD), stringent complete response (sCR), and very good partial response (VGPR) were significantly improved and similar in patients receiving either the combination of induction KRd for 4 cycles followed by ASCT followed by 4 cycles of KRd consolidation (KRd-ASCT-KRd) or KRd for 12 cycles (KRd-12) compared with those receiving the combination of induction carfilzomib/cyclophosphamide/dexamethasone (KCd) for 4 cycles followed by ASCT followed by 4 cycles of KCd consolidation (KCd-ASCT-KCd).2  


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In the FORTE study, patients eligible to receive maintanence therapy were randomly assigned (2:1) to receive lenalidomide (R) or carflizomib/lenalidomide (KR). This analysis of data from the FORTE study evaluated the efficacy of the KRd-ASCT-KRd and KRd-12 regimens in specific subgroups of patients based on disease risk according to the revised international staging system (R-ISS) for multiple myeloma.  The rate of early relapse (≤18 months from randomization) was also compared across these risk-based subgroups of patients receiving the 2 regimens.

Of the 158 patients randomly assigned to treatment with KRd-ASCT-KRd, 48 and 92 patients were classified as having R-ISS I and R-ISS II/III disease, respectively. Similarly, of the 157 patients receiving treatment with KRd-12, 39 and 94 patients were classified with R-ISS 1 and R-ISS2/3 disease. Median follow-up was 25 months.

A central finding of this analysis was that similar premaintenance rates of sCR, ≥CR, ≥VGPR, and MRD negativity were observed across disease risk groups for patients receiving KRd-ASCT-KRd compared with KRd-12. However, while the rate of 1-year persistent MRD negativity for those patients with confirmed results receiving KRd-ASCT-KRd was 90% in both risk groups, it was 85% and 72% for those treated with KRd-12 with low- and high-risk disease, respectively.

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Furthermore, in the overall group, significantly more patients receiving KRd-12 (26 participants) experienced early relapse compared with those receiving KRd-ASCT-KRd (12 participants; P =.015). While very few patients with RSS I disease experienced early relapse (0 participants [KRd-ASCT-KRd] vs 2 participants [KRd-12]), those patients with R-ISS stage II/III disease had a lower risk of relapse when treated with KRd-ASCT-KRd (11 participants, with 8 patients classified as MRD-positive) compared with KRd-12 (22 participants, with 17 patients classified as MRD-positive; P =.05).

On multivariate analyses, the risk of early relapse was significantly decreased for patients receiving KRd-ASCT-KRd compared with KRd-12 (odds ratio [OR], 0.21; 95% CI, 0.19-0.88); P =.022).

In her concluding remarks, Dr Gay stated that “both KRd with transplant and KRd without transplant are highly effective and induce high-quality responses. However, the rate of 1-year persistent MRD-negativity was lower in patients randomized to transplant and this difference was particularly evident in patients with high-risk disease.” She added that longer follow-up is needed to evaluate progression-free survival and overall survival.

Read more of Cancer Therapy Advisor‘s coverage of ASCO’s annual meeting by visiting the conference page.

References

  1. Gay F, Cerrato C, Petrucci MT, et al. Efficacy of carfilzomib lenalidomide dexamethasone (KRd) with or without transplantation in newly diagnosed myeloma according to risk status: Results from the FORTE trial. Presented at: 2019 American Association of Clinical Oncology (ASCO) Annual Meeting; May 31-June 3, 2019; Chicago, IL. Abstract 8002.
  2. Gay F, Cerrato C, Rota Scalabrini DR, et al. Carfilzomib-lenalidomide-dexamethasone (KRd) induction-autologous transplant (ASCT)-KRd consolidation vs KRd 12 cycles vs carfilzomib-cyclophosphamide-dexamethasone (KCd) induction-ASCT-KCd consolidation: analysis of the randomized Forte trial in newly diagnosed multiple myeloma (NDMM). Blood. 2018;132:121.