Patients eligible for transplant

ASH 2017 | Phase II Study of Ixazomib with Lenalidomide as post-ASCT maintenance therapy

The MM Hub were delighted to attend the 59th American Society of Hematology (ASH) Annual Meeting held in Atlanta, GA, from 9–12 December 2017. On Sunday 10 December 2017 an oral session was held: Session 653. Myeloma: Therapy, excluding Transplantation: Upfront Therapy for Multiple Myeloma: Induction and Maintenance and Abstract 437 was presented by Krina K. Patel and under the direction of Robert Z. Orlowski, from the Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX. The talk was entitled: Update on a Phase II Study of Ixazomib with Lenalidomide as Maintenance Therapy Following Autologous Stem Cell Transplant in Patients with Multiple Myeloma.

Krina Patel began her talk by explaining that lenalidomine maintenance (Len) used in the post autologous stem cell transplant (ASCT) setting has given highly promising data in Phase III trials to date, and that the use of proteasome inhibitors (PIs) in this setting is somewhat limited by the arduous means of IV administration. Therefore, ixazomib, an orally administered PI, could offer patients a more convenient alternative. Here, the updated results from a phase II study treating Newly Diagnosed Multiple Myeloma (NDMM) patients with Len combined with ixazomib (LenI), post-transplant, were reported. The primary objective to the study was to assess safety and efficacy, as well as the occurrence of secondary primary malignancies (SPMs), overall response rate (ORR) and toxicity.

Key points:
  • Patients (pts) were eligible post-ASCT having been treated with induction therapy of high-dose melphalan (within 12 months of initiation)
  • Pts began maintenance therapy 60-180 days’ post-ASCT
  • Treatment: 28-day cycles of ixazomib 4 mg (later amended to 3 mg) on days 1, 8, 15, and Len 10 mg daily on days 1-28 (Len increased to 15 mg after 3 months if well tolerated)
  • Patients (pts) (n= 64) were enrolled; median age = 60 (range 39-74)
  • At May 2017: 34/64 pts remain on therapy and had a median of 28 cycles (range 1-51)
  • ISS stage I = 32 pts had, stage II = 13; stage III = 9
  • Best overall response: sCR = 7.8%, CR = 26.5%, VGPR = 53% and PR = 10.9%
  • Median PFS = not reached; median follow up = 37.8 months
  • Estimated 2-year PFS = 81%
  • High-risk pts = 20; PFS of high-risk pts = not yet reached
  • Study discontinuation = 30 pts: Progressive Disease (PD) = 16 pts (8/16 were high-risk, 2 intermediate risk), PI discretion = 3 pts consent withdrawal = 11
  • Median PFS post-ASCT for these 16 pts = 17 months (3 to 43 months)
  • Death = 7 pts; OS = 4, 16 (2pts), 20 (2 pts), and 48 (2 pts) months
  • Adverse events (AEs): G1/2 peripheral neuropathy (PN) = 22 pts, G3 PN = 6 pts, SPMs = 3 pts DCIS of the breast = 1 pt, squamous cell carcinoma of the skin = 2 pts
  • Dose reductions in Ixazomib were given for a range of AEs, the most common being PN
  • Dose reductions in Len dose were predominantly given for neutropenia (12 pts)

Krina concluded by stating that this updated analysis further confirms the safety and manageability of long-term LenI maintenance post-ASCT, and offers a valid alternative for NDMM patients in the post-transplant setting.

References
  1. K. Patel et al. Update on a Phase II Study of Ixazomib with Lenalidomide as Maintenance Therapy Following Autologous Stem Cell Transplant in Patients with Multiple Myeloma. #Abstract 437. 59th ASH Annual Meeting and Exposition, Atlanta, GA.