ASH 2019 Day 3 – Combination Therapies for the Newly Diagnosed Session

DAY 3 – Evening Session 1 

Monday’s early evening session covered a variety of combination therapies all with the goal of improving the outcome for newly diagnosed multiple myeloma patients. All studies reported during this session investigated adding Darzalex into various standard combination regimens.

Incorporating Darzalex as a part of a 4-drug regimen was the focus of a presentation from Dr. Luciano Costa of the University of Alabama at Birmingham, who investigated the combination of Darzalex with Kyprolis-Revlimid-dexamethasone (DARA + KRd) in 81 newly diagnosed patients (ABSTRACT 860 https://ash.confex.com/ash/2019/webprogram/Paper123170.html). Dr. Costa used minimal residual disease (MRD) status to adapt therapy for patients. Patients received DARA + KRd as induction followed by ASCT, and DARA + KRd again as consolidation. At each phase of therapy, MRD status was measured. Patients received therapy until achievement of two consecutive MRD-negative remissions. Patients who were confirmed to be MRD-negative received no further therapy and were observed with surveillance for MRD resurgence.

  • All patients responded to induction treatment.
  • The MRD-negative remission rate was 40%, 74% and 82% after induction, transplant and consolidation, respectively. There were no differences in these rates if a patient had high-risk or standard-risk myeloma.
  • No patient discontinued therapy due to side effects.
  • All 26 patients who have achieved confirmed MRD-negative remission and discontinued therapy and none had relapse or resurgence of MRD with short follow up.

In the next study, DARA + KRd was also tested but this time using a weekly administration of Kyprolis. Typically, Kyprolis is administered bi-weekly. Dr. Ola Landgren from Memorial Sloan Kettering Cancer Center treated 39 patients with the weekly DARA + KRd regimen (ABSTRACT 862 https://ash.confex.com/ash/2019/webprogram/Paper126378.html).

  • All patients responded to treatment and 77% of patients achieved MRD negativity.
  • There were no added clinical side effects with the weekly administration compared to the biweekly.
  • There were fewer infusions using weekly versus biweekly administration.
  • A large randomized trial has now been developed to further evaluate weekly DARA + KRd as a treatment for newly diagnosed patients. Enrollment is to start by the end of this year.

Darzalex as maintenance therapy was the subject of a phase 2 trial called LYRA from Dr. Robert Rifkin of Rocky Mountain Cancer Centers. Patients on this study (87 newly diagnosed and 14 relapsed/refractory) were treated with the combination of Darzalex-cyclophosphamide-Velcade-dexamethasone (DARA + CyBorD) as induction followed by monthly Darzalex as maintenance (ABSTRACT 863 https://ash.confex.com/ash/2019/webprogram/Paper122497.html).

  • For newly diagnosed patients, 87% responded to induction treatment (79% of relapsed/refractory patients responded).
  • Response rates increased following maintenance therapy in those patients who underwent ASCT.
  • Patients who achieved a complete response or better lived longer before disease progression.
  • Low white blood cell counts was the most common side effect observed. Infusion reactions occurred in over half of the patients treated.

The last presentation of this session was on a phase 2 clinical trial that examined the safety and efficacy of the combination of Darzalex-Ninlaro-Revlimid-dexamathasone (DARA + IRd). In this regimen, the dose of dexamethasone has been modified in order to improve its tolerability. Dr. Prashant Kapoor from the Mayo Clinic reported the results of 40 newly diagnosed patients treated with this quadruplet regimen (ABSTRACT 864 https://ash.confex.com/ash/2019/webprogram/Paper131476.html).

  • 95% of patients responded.
  • All patients were alive and 90% were progression free at the last follow-up.

Treatment dose adjustments had to be made for a subset of patients mainly due to skin rash and side effects that affect blood counts.