Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma

Abstract

<jats:title>Abstract</jats:title> <jats:p>The impact of bridging therapy (BT) administered between leukapheresis and chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is unclear. We evaluated the influence of BT (systemic therapy [ST], radiation therapy [RT], or combined-modality therapy [CMT]) on outcomes of 148 LBCL patients who underwent leukapheresis for planned axicabtagene ciloleucel (axi-cel) infusion. The 55% (n = 81) of patients who received BT were more likely to have international prognostic index (IPI) score ≥3 (P ≤ .01), bulky disease (P = .01), and elevated lactate dehydrogenase (LDH; P ≤ .01). The 1-year progression-free (PFS) and overall survival (OS) rates were 40% and 65% in non-BT patients vs 21% and 48% in BT patients (P = .01 and .05, respectively). Twenty-four patients (16%) did not receive axi-cel, most commonly because of lymphoma progression (88%), despite 80% (n = 19) receiving BT. Among 124 patients who received axi-cel, 50% (n = 62) received BT with ST (n = 45), RT (n = 11), or CMT (n = 6); 1-year PFS and OS rates were not significantly different between BT and non-BT cohorts (P = .06 and .21, respectively). There was no difference in proportion of patients with IPI ≥3, limited-stage disease, or elevated LDH between ST, RT, and CMT groups. Compared with non-BT patients, 1-year PFS was inferior for ST-bridged patients (P = .01). RT-bridged patients had improved PFS compared with ST-bridged patients (P = .05). Despite the poor prognosis associated with requiring BT, RT can be an effective bridging strategy. Future studies are necessary to identify strategies that may improve access to CAR T-cell therapy and outcomes.</jats:p>

Navigating the narrow bridge to CAR T-cell therapy

“…In this issue, Pinnix et al compare the outcomes of 81 patients who received any bridging therapy prior to planned treatment with commercially available axicabtagene ciloleucel to 67 patients who did not. 3 Notably, the patients who received bridging therapy had worse 1-year progression-free survival (PFS) and overall survival than patients who did not. Bridging itself is unlikely to have led to worse outcomes; instead, the patients who needed bridging therapy were likely sicker than those who did not.…”

Use of cardiac radiation therapy as bridging therapy to CAR‐T for relapsed pediatric B‐cell acute lymphoblastic leukemia

“…Finally, in a phase 2 DLBCL study, BRT patients had higher overall response rate, less severe CRS, and less neurotoxicity compared to chemotherapy‐bridged patients 19 . These results and others suggest that priming with RT may be more effective than chemotherapy 20,21 . Our case differed from those reported in the above series in that our patient was in a clinically precarious situation, and the RT dose given (12 Gy) was selected to produce a local response as a bridge to CAR‐T, but also with the goal of avoiding significant late cardiac toxicity that may have occurred with a more definitive RT dose of 24‐30 Gy.…”

“…19 These results and others suggest that priming with RT may be more effective than chemotherapy. 20,21 Our case differed from those reported in the above series in that our patient was in a clinically precarious situation, and the RT dose given (12 Gy) was selected to produce a local response as a bridge to CAR-T, but also with the goal of avoiding significant late cardiac toxicity that may have occurred with a more definitive RT dose of 24-30 Gy. An earlier report showed that there may be a disease control advantage to irradiating all sites of disease prior to CAR-T as compared to only a subset of sites, though it remains unclear whether the potential toxicity of doing so could outweigh this benefit.…”

“…Our case differed from those reported in the above series in that our patient was in a clinically precarious situation, and the RT dose given (12 Gy) was selected to produce a local response as a bridge to CAR‐T, but also with the goal of avoiding significant late cardiac toxicity that may have occurred with a more definitive RT dose of 24‐30 Gy. An earlier report showed that there may be a disease control advantage to irradiating all sites of disease prior to CAR‐T as compared to only a subset of sites, though it remains unclear whether the potential toxicity of doing so could outweigh this benefit 20,21 . Our patient had widespread extramedullary disease also involving the kidneys, perineum, gluteal, and paraspinal tissues, and thus it would not have been feasible to treat all sites of disease; we therefore only treated those areas that were causing a significant local issue to improve symptoms and reduce the risk of adverse events after CAR‐T infusion, relying on CAR‐T to provide ultimate control of leukemia in unirradiated sites.…”

Immunotherapy with cells (article not eligible for CME credit)

“…14 Some data suggest that patients who receive bridging therapy while awaiting axi-cel have an outcome inferior to that of patients who do not receive bridging therapy. 10,15,16 Although bridging therapy may have a negative impact, it is more likely that this effect identifies a higher risk group of patients based on the need for disease control after T-cell collection. Theoretically, it is possible that immunosuppressive bridging therapy can enhance CAR-T expansion and persistence.…”