The impact of bridging therapy on outcomes following treatment with ide-cel in RRMM

Due to the complex nature of CAR T-cell manufacturing, which can span several weeks, bridging therapy (BT) between T-cell leukapheresis and lymphodepleting chemotherapy is often necessary. BT is vital for disease control during the CAR-T manufacturing process and to potentially reduce CAR-T-associated toxicities, decrease disease burden, and improve response durability.¹

Here, we summarize a study by Afrough et al.,¹ published in Blood Cancer Journal, on the impact of different BTs on outcomes in patients with relapsed/refractory multiple myeloma (RRMM), treated with standard-of-care idecabtagene vicleucel (ide-cel).¹

Study design¹

• This retrospective study examined the impact of BT use and type prior to ide-cel treatment, in terms of ide-cel response and survival.
• Patients with RRMM who were being treated with ide-cel across the U.S. Myeloma Immunotherapy Consortium were included.

Key findings¹

• Of the 214 patients treated with ide-cel, 170 received some form of BT.
• Overall, patients who did not receive BT experienced increased median overall survival (OS) and progression-free survival (PFS) (Table 1).
• Patients receiving a BT also experienced higher rates of neutropenia and anemia than those who did not receive BT at 3 months post-infusion.
  • Any-grade neutropenia: 47% vs 27.5%, respectively.
  • Any-grade anemia: 79% vs 50%, respectively.
• The use of alkylators as BT was associated with the poorest OS rates, with median OS not reached, of any BT within the follow-up period (Table 1).
• Alkylators were also associated with the poorest PFS rates, despite there being no significant difference in either tumor burden or inflammatory markers at initiation.
• Response rates did not differ significantly between BT subgroups (Figure 1).
• The highest rates of immune effector cell-associated neurotoxicity at Grade ≥2 were observed in patients who received selinexor BT compared with alternatives:
  • Selinexor, 38%
  • Alkylators, 9%
  • Proteasome inhibitor combinations, 0%
  • Immunomodulatory agent combinations, 17%
• Of the total cohort, 70 deaths occurred, with the most common cause being disease-related, followed by infection.

Table 1. Median progression-free survival and overall survival by bridging therapy*