HISTOLOGICAL CHARACTERISTICS, TREATMENT PATTERNS, AND OUTCOMES FOLLOWING DISEASE PROGRESSION AFTER CAR-T THERAPY IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA

Abstract

H. S. Raman equally contributing author.

Introduction: CD19-directed CAR T-cell therapy (CAR-T) has demonstrated outstanding therapeutic activity in patients (pts) with refractory/relapsed (R/R) follicular lymphoma (FL). However, data regarding histological features, treatment patterns, and outcomes of pts with disease progression (POD) following CD19 CAR-T therapy for R/R are poorly understood.

Methods: Characteristics of 101 pts receiving CAR-T for FL were collected across 4 international centers. Pts with FL grade 3B or any prior history of histological transformation were excluded.

Results: We identified 25 pts (24.8%) who experienced POD after CAR-T. Median age at infusion was 62 years (range 34–79). Pre CAR-T FL grade was 1–2 in 76% of the pts, grade 3A in 12%, and unavailable in 12%. Median prior therapy lines were 3 (range 2–7). Administered products were axicabtagene ciloleucel (84%), tisagenlecleucel (12%), and lisocabtagene maraleucel (4%), predominantly as SOC (96%). High-risk features before CAR-T were common: 40% had experienced POD24, 68% were refractory to their last therapy, including 32% with primary refractory disease. Among pts with post-CAR-T POD, the best post-infusion response was CR in 56%, PR in 20%, and stable or progressive disease in 24%. The median time from CAR-T infusion to POD was 8.9 months (IQR 3–15).

Following POD, 20 pts received systemic therapy (median 1 line, range 1–7), 3 remain on active surveillance, 1 received palliative care, and 1 was lost to follow-up. The ORR after initial post-POD therapy was 72% among evaluable pts. Administered therapies included CD3×CD20 bispecific antibodies (BsAbs) (n = 10; 8 evaluable, ORR 88%, CR 63%), chemoimmunotherapy (n = 6, ORR 83%, CR 50%), tafasitamab-based combinations (lenalidomide, n = 1; tazemetostat, n = 1; no response), lenalidomide + obinutuzumab (n = 1; no response), and investigational agent (n = 1; ORR 100%). Three pts underwent allogeneic SCT as consolidation and are still in remission.

In 18 pts with post-CAR-T POD histologic documentation, 3 had transformed FL to diffuse large B-cell lymphoma, 1 had FL grade 3B, and 14 had relapsed FL grade 1–3A. CD19-negative disease was found in 1 pt, while 5 (28%) had CD20-negative disease (3 pre-CAR-T exposed to CD3xCD20 BsAb).

Median follow-up for the entire cohort and from POD was 24 and 16 months, respectively. Median progression-free survival post CAR-T POD was 19 months (95% CI: 10–28) with an estimated 1-year PFS of 68% (95% CI: 50–91). During follow-up, 5 pts (18%) died, all due to disease progression. Median overall survival from POD was not reached, with an estimated 1-y OS of 86% (95% CI: 73–100) (Figure).

Conclusions: To our knowledge, this represents the largest cohort of FL pts with POD post-CAR-T. BsAbs showed promise in this setting, but longer follow-up is needed for durability assessment. The mechanisms associated with risks of POD post-CAR-T and histological transformation warrant further study.

Keywords: indolent non-Hodgkin lymphoma

Potential sources of conflict of interest:

L. Falchi

Consultant or advisory role: Roche, Genentech, Genmab, AbbVie, Sanofi, Evolveimmune, Astrazeneca, Merck, ADC therapeutics, Seagen, Ipsen, Johnson & Johnson

Honoraria: Roche, Genmab, AbbVie, Kite

Educational grants: Genmab, AbbVie, Roche, Kite

Other remuneration: Research funding: Roche, Genentech, Genmab, AbbVie, Innate Pharma, Beigene AstraZeneca

C. A. Jacobson

Consultant or advisory role: Kite/Gilead, BMS, Novartis, ADC Therapeutics, Abbvie, AstraZeneca, Janssen, Appia Bio, Aleta, Umoja, Kyverna, Miltenyi, Caribou, Galapagos, Sana, Synthekine, GenmAb, Genentech, Autolus

M. L. Palomba

Consultant or advisory role: Bristo Meyer Squibb, Novartis, Synthekine, Cellectar

R. W. Merryman

Consultant or advisory role: DG Medicine, Bristol Myers Squibb, KITE, Abbvie, Ipsen

Honoraria: Abbvie, Genmab

G. Salles

Consultant or advisory role: AbbVie, ATB Therapeutics, BeiGene, BMS/Celgene, Debiopharm, Genentech/Roche, Genmab, Incyte, Ipsen, Janssen, Kite/Gilead, Loxo/Lilly, Merck, Molecular Partners