For patients with relapsed/refractory large B-cell lymphoma (LBCL) who progress after CAR-T therapy, salvage treatment with polatuzumab-containing and bispecific antibody-based regimens is preferable to standard chemotherapy, according to findings presented at the 64^th American Society of Hematology (ASH) Meeting & Exposition. 

These findings were presented by lead author of the study, Gloria Iacoboni, MD, Vall d’Hebron University Hospital, Barcelona, Spain.

The study included 217 patients from 12 sites who had a confirmed progression after CAR-T therapy at ≥1 month of follow-up. Of these patients, 79 (36%) received palliative care (non-treatment group) and 138 (64%) received treatment (treatment group). Among patients who received treatment, 31 received rituximab-polatuzumab-bendamustine, 27 received bispecific antibodies, 27 received standard chemotherapy, 23 received immune checkpoint inhibitors, 17 received radiotherapy, and 4 received lenalidomide-based regimens. 

Researchers analyzed baseline characteristics, response rates across treatments, and survival outcomes were analyzed. Univariate and multivariate logistic regression were conducted to evaluate the impact of baseline characteristics on receipt of treatment following CAR-T progression.

Median follow-up since relapse or progression was 17 months for the full cohort. Findings from univariate analysis showed that age, pretreatment IPI score, ECOG performance status, achievement of an initial response after CAR-T progression, and time from infusion to progression were all baseline characteristics that had a significant impact on receipt of treatment following CAR-T progression. Findings from multivariate analysis showed age retained this significant impact (P = .003).

After first-line salvage treatment, best response included an overall response rate (ORR) of 62% for polatuzumab vedotin-based treatment, 48% for bispecific antibody-containing treatment, 32% for immune checkpoint inhibitors, and 27% for standard chemotherapy. Complete response (CR) rates were 38%, 33%, 23%, and 16%, respectively.

Median PFS for the full treatment group was 3.1 months and 12-month PFS was 18%. Median PFS was 6.1 months for the polatuzumab vedotin-based treatment group, 4.7 months for the bispecific antibody-containing treatment group, 2.7 months for the immune checkpoint inhibitor group, and 2.1 months for the standard chemotherapy group. Researchers noted that the polatuzumab regimen was the only treatment to show a significant improvement in PFS (P = .02) vs standard chemotherapy.

Median OS for the full cohort was 5 months and was significantly longer in the treatment group (7.6 months) vs the non-treatment group (1.1 months; P <.01). The 12-month OS was 35% vs 7%, respectively. Time from CAR-T infusion to disease progression showed significant difference in OS, those who experienced disease progression <2 months from infusion had an OS of 3 months, 2 to 6 months from infusion had an OS of 5.9 months, and >6 months from infusion had an OS of not reached (P <.01).

In the treatment group, 15 (11%) patients received allogeneic hematopoietic stem cell transplant (alloHSCT) as consolidation after responding to salvage treatment with standard chemotherapy (n = 7, 26%), polatuzumab-containing regimen (n = 4, 13%), radiotherapy (n = 3, 18%), or bispecific antibody-based regimen (n = 1, 4%). With a median follow-up after alloHSCT of 11.1 months, 3 patients had progressed and 4 had died. Median OS was not reached.

“Salvage strategies with polatuzumab-containing regimens and bispecific antibody-based trials yield higher response rates in comparison to standard chemotherapy [for patients with LBCL progressing early after CAR-T therapy],” concluded Dr Iacoboni and colleagues. 

“Consolidation with an alloHSCT after achieving a response in this setting should be discussed in all potential candidates,” they added.

Source:

Iacoboni G, Iraola-Truchuelo J, Mussetti A, et al. Salvage Treatment with Novel Agents Is Preferable to Standard Chemotherapy in Patients with Large B-Cell Lymphoma Progressing after Chimeric Antigen Receptor T-Cell Therapy. Presented at the ASH Annual Meeting & Exposition; December 10-13, 2022; New Orleans, Louisiana, and virtual. Abstract 155.