Safety and Efficacy of Relmacabtagene Autoleucel (relma-cel) in Adults with Relapsed/Refractory Mantle Cell Lymphoma (r/r MCL): Updated Results from a Phase II Open-Label Study in China

Background: Mantle cell lymphoma (MCL), an aggressive subtype of B-cell non-Hodgkin lymphoma, predominantly affects elderly males. Poor overall response rates (ORR) and high rates of recurrence are observed for those patients after discontinuation or failure from Bruton 's tyrosine kinase inhibitors (BTKi), with median overall survival (OS) of 6~10 months. A phase II open label study (NCT04718883) for relma-cel reported the first efficacy and safety data in 11 Chinese patients with relapsed/refractory Mantle Cell Lymphoma (r/r MCL) in ASH 2022. This abstract provides the updated data based upon 56 patients. The study is still ongoing.

Methods: The study enrolled patients with confirmed diagnosis of MCL, relapsed or refractory after at least 2 lines of prior therapies including anti-CD20 antibody, anthracycline or bendamustine, andBTKi. After lymphodepleting chemotherapy, patients received relma-cel (100×10 ⁶ CAR+ Tcells). Bridging therapy was allowed. Primary endpoint was ORR at month 3 assessed by investigator, and secondary endpoints included complete response rate (CRR) at month 3, duration of response (DoR), progression-free survival (PFS), OS, pharmacokinetics (PK), pharmacodynamics (PD) and safety.

Results: As of June 30, 2023, 66 patients enrolled and receivedleukapheresis. Relma-cel was administered in 56 patients (78.6% males; median age of 59.5 years). 42 patients had tumor assessment at month 3 or discontinued treatment due to death, disease progression before evaluation. The study population had poor prognostic factors at baseline:

• Age: 19 (33.9%) ≥ 65 years old

• Pathology: 13 (23.2%) with blastoid and 6 (10.7%) with pleomorphic variants

• 30 (53.6%) with extranodal lesions, 4 (7.1%) with gastrointestinal involvement; 28 (50.0%) with spleen involvement, 17 (30.4%) with bone marrow involvement

• MCL International Prognostic Index (MIPI) score ≥ 4: 27 (48.2%)

• High tumor burden: 17 (30.4%) had bulky disease ≥ 5 cm

Over 65% patients received ≥ 3 lines of prior therapies, including 25.0% patients received ≥ 5 lines. Almost all patients failed to BTKi (29 [51.8%] relapsed and 25 [44.6%] refractory). Seven (12.5%) patients relapsed after hematopoietic stem cell transplantation (HSCT). Twenty-six (46.4%) patients underwent bridging therapy.

At month 3, of the 42 efficacy-assessable patients, 27 (64.29%) reached objective responses (OR), and 23 (54. 76%) achieved complete response (CR). Best ORR was 78.57% and best CRR was 66.67%.

Based on the safety analysis set of 56 patients, 52 (92.86%) patients had treatment emergent adverse events (TEAE), including 44 (78.57%) with treatment related TEAE of grade ≥ 3. Twenty-five (44.64%) patients had serious adverse events (SAE), and 13 (23.21%) with treatment related SAE. Thirty-one (55.36%) patients had cytokine release syndrome (CRS), 3 (5.36%) with grade ≥ 3. Six (10.71%) patients had neurotoxicities (NT), 4 (7.14%) with grade ≥ 3. Twenty-seven (48.21%) patients had infections, 15 (26.79%) with grade ≥ 3. Forty-seven (83.93%) patients had prolonged cytopenia, 38 (67.86%) with grade ≥ 3. Eighteen (32.1%) deaths occurred, 6 (10.7%) died from disease progression, 8 (14.3%) due to AE, 2 (3.6%) died from treatment related AE, 4 (7.2%) from other reasons or unknown causes.

Conclusions: In this phase II study, relma-cel continually demonstrated high response rates (best ORR: 78.57%; best CRR: 66.67%) and good tolerability in patients with r/r MCL.