Meta-analysis of response rates to first-line salvage treatment after CAR-T therapy failure in large B-cell lymphoma patients

ABSTRACT

Introduction

The prognosis for large B-cell lymphoma (LBCL) patients who did not respond or relapsed after chimeric antigen receptor (CAR)-T therapy remains dismal, with no established consensus on the most effective salvage regimen.

Methods

We conducted a random-effects meta-analysis of complete response (CR) and overall response rates (ORR) to first-line treatments for CAR-T-relapsed/refractory LBCL. We followed the predefined protocol available at PROSPERO (CRD42023473854).

Results

We identified 41 studies evaluating the following interventions: non-CD19 CAR-T, CD19 CAR-T, bispecific antibodies (BiTEs), lenalidomide- and polatuzumab-based regimens, radiotherapy, immune checkpoint inhibitors (ICI), Bruton’s Tyrosine Kinase inhibitors (BTKi). Non-CD19 CAR-T cells yielded the best CR (56%, CI: 40–71%), significantly higher than other interventions except CD19 CAR-T (CR = 30%, CI: 7–58%). BiTEs, radiotherapy, lenalidomide- and polatuzumab-based regimens (CR: 28%, 26%, 19%, 24% respectively) did not differ significantly from each other. ICI and BTKi showed the lowest CR rates (12%, CI: 5–20% and 8%, CI: 0–23%, respectively), and were also significantly inferior to BiTEs. ORR was the highest for non-CD19 CAR-T (ORR = 80%, CI: 66–92%), whereas all other regimens yielded values below 50%.

Conclusions

Non-CD19 CAR-T cells were associated with higher response rates and should be considered if patients are eligible. Given the heterogeneity of the estimates, the results should be interpreted cautiously.

Registration

PROSPERO CRD42023473854

KEYWORDS:

• CAR-T
• LBCL
• lymphoma
• meta-analysis
• response rate

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received honoraria for advisory boards from Kite, a Gilead company and BMS. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

Conceptualization and methodology – J Tomasik, GW Basak.; Literature search – J Tomasik, D Bilicki; Record screening and data extraction – J Tomasik, D Bilicki; Statistical analysis – J Tomasik; Manuscript Writing – all authors, Supervision – GW Basak.

Supplementary materials

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14712598.2024.2354371

Additional information

Funding

This paper was not funded.