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KRd Regimen Shows Promise in Newly Diagnosed Myeloma

Jason Harris
Published: Wednesday, Sep 05, 2018

Francesca Gay, MD, PhD

Francesca Gay, MD, PhD

The combination of carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) may represent a new standard of care for patients with newly diagnosed multiple myeloma, including those with high-risk disease, said Francesca Gay, MD, PhD.

, Gay reviewed the results of the FORTE trial and discussed how including MRD assessment and risk status can make clinical trials more valuable for patients.

OncLive: Can you give an overview of the FORTE results?

Gay: We saw that, by an intent-to-treat analysis, the rate of PR after induction was very high in both arms at around 90%. However, the objective response was higher in patients treated with KRd; they achieved a significantly higher rate of VGPR, near CR, at least VGPR, at least near CR, and CR/stringent CR. This was true not only in the overall population of patients, but also in the high-risk subgroup, defined as those with high-risk fluorescence in situ hybridization or International Staging System (ISS) stage II/III disease or with revised ISS stage II/III disease. The rate of response was also comparable with the overall population.

. We saw that in the subset of patients for whom the data were available, 50% of the patients on KRd achieved MRD negativity versus 30% with KCd. This difference was significant. The rate of MRD negativity was similar in high-risk patients and comparable with the overall population.

Based on these findings, what are the next steps?

These results demonstrate that this regimen is highly effective, so we need to probably wait for the survival data before deciding on the next step. However, these results are promising for our patients including those who are at high risk—a group that currently represents an unmet medical need.

What do you want community oncologists to take away from these results?

We have again demonstrated the efficacy of combining proteasome inhibitors and immunomodulatory agents. The second-generation proteasome inhibitor carfilzomib works very well and may be safer because we did not have an unexpected rate of toxicity. If the survival data confirm these results, I hope we have a new standard of treatment; however, it is not currently available everywhere.

What is the current prognosis and standard of care for this patient population?

The current standard of care varies in different countries based on regulatory approval. The current standard of care, however, is the combination of the proteasome inhibitors and immunomodulatory agents. In Europe, what is approved is bortezomib/thalidomide/dexamethasone. We hope soon to add the combination of bendamustine/lenalidomide/dexamethasone, which is available in the United States. This is the induction, then the current standard is to move to autologous stem cell transplant.

What would you like to see happen in the field over the next 5 to 10 years?

We should start to prospectively evaluate the role of MRD within clinical trials and design studies that adopt a treatment strategy according to MRD response achieved and the patient's baseline risk. That is something we are working on, but we still do not have trials that provide us with these answers.
Gay F, Scalabrini DR, Belotti A, et al. Updated efficacy and MRD data according to risk-status in newly diagnosed myeloma patients treated with carfilzomib plus lenalidomide or cyclophosphamide: results from the FORTE trial. In: Proceedings from the 2018 EHA Congress; June 14-17, 2018; Stockholm, Sweden. Abstract S109.

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