KarMMa-9: Idecabtagene vicleucel plus lenalidomide for the treatment of NDMM with suboptimal response to ASCT

Patients with newly diagnosed multiple myeloma (NDMM) who experience an incomplete response to autologous stem cell transplantation (ASCT) have poorer outcomes, with an increased risk of progression (38%) and an increased risk of death (41%) compared with patients who experience a complete response.¹ KarMMa-9 (NCT06045806) is an ongoing phase III trial comparing the efficacy and safety of idecabtagene vicleucel (ide-cel) plus lenalidomide for maintenance vs lenalidomide alone in patients with NDMM who had a suboptimal response (partial response or very good partial response) to ASCT.

Here we summarize a poster presentation by Mateos, et al.¹ from the 5th European Myeloma Network Meeting, 2024, on the rationale and study design of the phase III KarMMa-9 trial.¹

Study design and key findings¹

• KarMMa-9 is an ongoing multicenter, randomized trial, currently enrolling across 19 countries.
• Eligibility criteria include:
  • Patients with NDMM
  • Aged ≥18 years
  • East Cooperative Oncology Group (ECOG) performance status of 0–2
  • Received 4–6 cycles of induction therapy
  • Single ASCT 80–120 days prior to study treatment
  • ‘Partial response’ or ‘very good partial response’ post-ASCT at the time of consent
  • No prior maintenance after ASCT

• The primary endpoint is progression-free survival (PFS) per the independent review committee (IRC).
• The key secondary endpoint is overall survival (OS) The other secondary endpoints include measurable residual disease-negative complete response rate, event-free survival, duration of response, complete response rate per IRC, time to progression per IRC, PFS2, time to next treatment, safety, health-related quality of life, and pharmacokinetics.
• Key safety outcomes include AE reporting.
• Patients will be randomly assigned to receive ide-cel plus lenalidomide or standard-of-care lenalidomide maintenance (Figure 1).
  • Combining ide-cel with standard-of-care maintenance therapy is expected to improve clinical outcomes and extend PFS in patients with clinically high-risk NDMM.
• Randomization will be stratified, based on the stage of disease, induction therapy, and the degree of treatment response post-ASCT.

CAR, chimeric antigen receptor; ide-cel, idecabtagene vicleucel; LDC, lymphodepleting chemotherapy; OS, overall survival; PD, progressive disease; PFS, progression-free survival.
*Adapted from Mateos, et al.^1
†Apheresis to be performed within 14−42 days after last dose of R.
^‡Fludarabine 30 mg/m² and cyclophosphamide 300 mg/m² on Days -5, -4, and -3 prior to ide-cel infusion.

• The trial was initiated in October 2023 and is currently recruiting at 118 sites in 19 countries.
  • Australia, Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Greece, Israel, Italy, Japan, Korea, Norway, Poland, Romania, Spain, United Kingdom, and the USA
• A total of 618 eligible patients with NDMM have been enrolled so far.

Key learnings1
KarMMa-9 trial will compare the efficacy and safety of ide-cel and lenalidomide as a combination therapy vs lenalidomide alone in patients with NDMM who experience an incomplete response to ASCT. Ide-cel combined with standard-of-care maintenance therapy is expected to improve clinical outcomes and prolong PFS in this high-risk population.