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

• Published in: Blood advances Vol. 4; no. 13; pp. 2871 - 2883
• Main Authors: Pinnix, Chelsea C., Gunther, Jillian R., Dabaja, Bouthaina S., Strati, Paolo, Fang, Penny, Hawkins, Misha C., Adkins, Sherry, Westin, Jason, Ahmed, Sairah, Fayad, Luis, Lee, Hun Ju, Nair, Ranjit, Steiner, Raphael E., Iyer, Swaminathan P., Rodriguez, M. Alma, Wang, Michael, Flowers, Christopher, Neelapu, Sattva S., Nastoupil, Loretta J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.07.2020; American Society of Hematology
• Subjects: Antigens, CD19 - therapeutic use; Biological Products; Clinical Trials and Observations; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse - drug therapy; Survival Rate
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2020001837

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. •Bridging therapy before CAR T-cell therapy is pursued in high-risk patients, including those with high IPI, elevated LDH, and bulky disease.•Radiation therapy can be an effective bridging option for disease control before CAR T-cell therapy. [Display omitted]