Panobinostat, gemcitabine, busulfan, and melphalan salvage therapy in RRMM

The standard-of-care for patients undergoing consolidation of frontline therapy in multiple myeloma (MM) is currently high-dose melphalan with autologous stem cell transplantation (ASCT). Progression-free survival (PFS) rates were observed to increase with the addition of busulfan (BuMel), and again with the addition of gemcitabine (GemBuMel). Individuals receiving salvage therapy often experience relapse, therefore novel combinations are continuing to be investigated for applicability in these patients.¹

Here, we summarize a study published by Nieto et al.¹ in American Journal of Hematology on the safety and efficacy of high-dose panobinostat combined with GemBuMel therapy following ASCT salvage in relapsed/refractory or high-risk MM.

Study design¹

• Patients with high-risk or relapsed/refractory MM and adequate end-organ function were enrolled into two cohorts depending on whether they were receiving their first ASCT (ASCT-1) (n = 48) or second transplant (ASCT-2) (n = 32).
• Panobinostat was administered orally at 20 mg/day in addition to GemBuMel
• The matched control cohort for ASCT-1 (N = 299), included treatment with BuMel (n = 122) or melphalan (n = 177), and for ASCT-2, included BuMel (n = 19) or melphalan (n = 53).
• The primary endpoint was PFS
• Secondary endpoints included were overall response rate, stringent complete response, overall survival (OS), measurable residual disease (MRD), and toxicity profile.

Key findings¹

• At a median follow-up of 51 months, the median PFS of the ASCT-1 and -2 cohorts were 25 months and 32 months, respectively.
• Median OS was not reached in either cohort
• Transplant-related mortality was recorded in two patients in the ASCT-2 cohort, and none in the ASCT-1 group.
• The toxicity profile was deemed acceptable, and not significantly different to the matched control groups.
• In both cohorts, MRD negativity increased following ASCT, with an improvement of 8.5% to 23% in ASCT-1, and 34% to 55% in ASCT-2
  • Increased rates of MRD negativity correlated with improved outcomes
• ASCT-1 and -2 cohorts compared with matched controls:
  • In both ASCT-1 and -2 cohorts, increased PFS rates were observed compared with the control groups (p = 0.025 and p = 0.04, respectively). More information and data representation can be found here
  • OS rates were not significantly different in either of the matched groups
• PFS and OS rates at 1-year post-ASCT, as well as response data are presented in Figure 1.

Figure 1. 1-year PFS, OS, and response rates* 

ASCT, autologous stem cell transplantation; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; sCR, stringent complete response.
*Data from Nieto, et al.¹