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*

BT, bridging therapy; IMiD, immunomodulatory agent; NR, not reached; OS, overall survival; PFS, progression-free survival; PI, proteasome inhibitor. *Adapted from Afrough, et al.1
Median survival, months	Bridging therapy			Type of bridging therapy
	Yes	No		No BT	Selinexor	Alkylator	PI combo	IMiD combo
PFS	6.68	11.48		11.48	9.77	6.51	6.41	12.01
OS	13.85	NR		NR	NR	11.97	NR	NR

BT, bridging therapy; CR, complete response; IMiD, immunomodulatory agent; MRD, measurable residual disease; ORR, overall response rate; PI, proteasome inhibitor.
*Data from Afrough, et al.¹

Key learnings1

Patients who received a BT before ide-cel experienced poorer PFS and OS, which may be indicative of more aggressive disease in these patients. Alkylator-based BTs were associated with poorer PFS and OS compared with other BTs. However, this observed trend may be associated with more refractory disease, highlighting a potential benefit of earlier use of CAR T-cell therapies. Overall, these data demonstrate the importance of individualized treatment plans based on patient-related factors, treatment history, and toxicity risks.