Ixazomib treatment regimens in NDMM patients: oral abstracts at SOHO 2017

The fifth Annual Meeting of the Society of Hematologic Oncology (SOHO) took place at the Westin Galleria in Houston, Texas, from the 13^th to the 16^th September 2017.

SOHO was established in 2012, with its main aim being “to promote worldwide research, education, prevention, clinical studies and optimal patient care in all aspects of hematologic malignancies and related disorders.” SOHO has over 2,000 members and is led by a Board of Directors with six voting members, a Steering Committee of clinician-scientists, a Scientific Committee, and an Education Committee.

The 2017 meeting was attended by numerous internationally recognized speakers representing the wide spectrum of hem-onc diseases, as well as over 1,000 physicians, nurses, and related healthcare specialists.

On Thursday, September 14^th, the sixth session was dedicated to Multiple Myeloma (MM), chaired by Sagar Lonial from The Winship Cancer Institute, The Emory University School of Medicine, USA, and co-chair of the MM Hub, and Robert Orlowski from The University of Texas, MD Anderson Cancer Center, USA. Two oral abstracts focussing on Ixazomib treatment regimens were presented.

Abstract MM-135: An Open-label, Phase 2 Study to Evaluate the Oral Combination of Ixazomib, Cyclophosphamide, and Dexamethasone (ICd) in Transplant-ineligible Patients with Newly Diagnosed Multiple Myeloma (NDMM)¹

This abstract was presented by Meletios Dimopoulos from The National and Kapodistrian University of Athens and a member of the MM Hub steering committee. This main aim of this trial was to evaluate the all-oral ICd regimen as a tolerable combination for patients that may not be eligible for immunomodulatory regimens, with the primary endpoint being complete response (CR), and very good partial response (VGPR) during induction.

• Patients (pts) were given dexamethasone 40 mg weekly, for up to 13 x 28-day cycles, and randomized to receive - oral ixazomib 4.0 mg and oral cyclophosphamide as either: Arm A = 300 mg/m² or Arm B = 400 mg/m², on days 1, 8, and 15; pts with ≥ SD and an acceptable toxicity profile then received ixazomib maintenance
• 70 NDMM pts were enrolled with characteristics well balanced between treatment arms
• Median Number of cycles = 19 at data cut-off (June 29^th 2016); 66% had completed 13 x ICd induction cycles and proceeded to ixazomib maintenance; 47% were ongoing and 53% had discontinued due to AEs (24%)

Data is given as Arm A vs Arm B:

• CR (induction and overall): 12% and 15% vs 9% and 12%
• VGPR (induction and overall):  15% and 21% vs 15% and 18%
• CR + VGPR (induction and overall): 27% and 36% vs 24% and 29%
• Median time to first response/≥VGPR = 2/4 months
• Median PFS = 23.5 vs 23.0 months (April 17, 2017)
• Median follow-up = 26.8 vs 25.6 months
• Combined PFS estimates at 12, 18 and 24 months = 81%, 67%, 49%
• 24-month PFS = 49% vs 50%
• Reported AEs = 94% vs 100%; Grade 3 = 72% vs 74%; SAEs = 47% vs 56%
• Common grade ≥3 AEs (both Arms):  neutropenia = 31%, anemia = 14%, lower respiratory tract and lung infections = 13%, and supraventricular arrhythmias = 7%
• Number of deaths = 5; none were considered treatment-related

In conclusion, this convenient oral regimen shows beneficial effects along with a tolerable safety profile. A comparison of the two tested doses for cyclophosphamide indicates that 300 mg/m² should be used for future phase 3 trials.

Abstract MM-143: Twice-weekly Ixazomib plus Lenalidomide-dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Long-term Follow-up Data for Patients Not Undergoing Stem Cell Transplantation (SCT)²

This abstract was presented by Paul G. Richardson from the Dana-Farber Cancer Institute, Boston, USA and gave data from a phase I/II study to assess the oral proteasome inhibitor, ixazomib, in combination with lenalidomide and dexamethasone (Rd) in newly diagnosed Multiple Myeloma Patients (NDMM). Ixazomib (escalating doses of 3.0 or 3.7 mg on days 1, 4, 8, and 11) plus Rd was administered twice-weekly as induction for 16 x 21-day cycles, followed by twice-weekly ixazomib maintenance in NDMM patients that were either SCT-eligible or ineligible. Long-term efficacy and safety was assessed in patients that were not withdrawn for SCT. The primary endpoint was complete response (CR) plus very good Partial Response (VGPR).

• Patients (pts) enrolled = 64; 41 were not withdrawn for SCT; 18 received single-agent ixazomib maintenance (post-induction)
• Median follow-up = 47.0 months

Data are given as Pts not withdrawn for SCT vs Maintenance subset:

• Median number of treatment cycles = 13 vs 31.5
• ORR (≥PR) = 92% (n= 39) vs 94%; CR + VGPR = 69% (n= 39) vs 89%
• Median PFS = 24.9 months (pts not withdrawn for SCT)
• Median OS = not estimable (3-year estimate = 86%)
• Pts improved their responses during maintenance
• Pts with Grade ≥ 3 AEs: 85% vs 44%
• Data for AEs is given as Pts not withdrawn for SCT vs Maintenance subset: onset during induction (cycle 1-16) and onset during maintenance (cycle ≥17)
• Most common Grade ≥ 3 AEs: Hyperglycemia = 15% vs 11% and 6%; Rashes, eruptions, and exanthems = 17% vs 22% and 6%
• Any SAE: 54% vs 56% and 11%; AEs leading to dose reductions = 66% vs 72% and 33%

In conclusion, treatment of patients with twice-weekly ixazomib plus Rd gave good response rates in those not withdrawn for SCT and who received ixazomib maintenance therapy. AEs more commonly occurred during induction, with infrequent incidence during maintenance.