Preliminary Safety and Efficacy of Relmacabtagene Autoleucel (relma-cel) in Adults with Relapsed/Refractory Mantle Cell Lymphoma (r/r MCL) in China

Background: MCL is an aggressive subtype of B-cell non-Hodgkin lymphoma with median overall survival (OS) of approximately 3-4 years from diagnosis. However, OS is even shorter (6~10 months) after discontinuation or failure from Bruton's tyrosine kinase inhibitors (BTKi) and these patients have poor overall response rates (ORR) and high rates of recurrence. Relma-cel is a CD19 directed CAR-T product, and here we report the first results of relma-cel from a phase II single arm study (NCT04718883) in adults with r/r MCL.

Methods: Patients with confirmed MCL, relapsed or refractory after at least 2 lines of therapy including anti-CD20 antibody, anthracycline or bendamustine, and BTKi were enrolled. After lymphodepleting chemotherapy, participants received relma-cel (100×10⁶ CAR+ Tcells). Bridging therapy was allowed. Primary endpoint was ORR at month 3, 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 Nov 30, 2021, 35 participants were enrolled. Relma-cel was manufactured for 24 participants and administered to 18. A total of 11 participants completed 3 months follow-up. Based on the analyses set of the 11 participants, the median age was 57 years old (min-max: 46-72), and 9 participants (81.8%) were male. Many had poor prognostic factors at baseline, including 5 (45.5%) age >65 years, organ involvement [5 bone marrow, 3 spleen, 1 lung, 1 gastrointestinal tract], 6 (54.5%) had Mantle-Cell Lymphoma International Prognostic Index (MIPI) score >3, and 5 had blastoid and 1 pleomorphic variants. High tumor burden was observed in 2 (sum of the products of diameters [SPD] of 14,251 and 19,124 mm²). Participants received up to 7 lines of prior therapies (9/11 [81.8%] ≥ 3 lines; 4/11 [36.4%] ≥ 5 lines), and 9/11 (81.8%) had progressed after the last line. All 11 participants received and failed BTKi, and the median line of BTKi-based therapy was 3. Three participants (27.3%) underwent bridging therapy, Platinum or Cytarabine or combination (Table 1).

Of the 11 efficacy assessable participants, 8 participants had partial response (PR) or complete response (CR) (ORR 72.7%) and 6 achieved CR (CRR 54.5%) at month 3 landmark evaluation. Best ORR was 81.8% and best CRR was 54.5%.

All 11 participants had treatment emergent adverse event (TEAE), which were assessed by investigator as treatment related TEAE, including 9 participants with treatment related TEAE of grade ≥3. Five participants had serious adverse event (SAE), and 2 of them experienced relma-cel related SAE. Six participants (54.5%) had cytokine release syndrome (CRS), including 1 grade ≥3. Two participants had immune effector cell-associated neurotoxicity syndrome (ICANS), including 1 grade ≥3. Two deaths occurred. One died after disease progression, and the other died from pulmonary infection. Safety data and PK parameters are shown in the Table 2.

Conclusions: In this phase II study in China, the preliminary data of relma-cel provided promising clinical efficacy outcome (best ORR 81.8%, best CRR 54.5%) in high risk patients with r/r MCL and a low incidence of grade ≥3 CRS and ICANS. This study is ongoing and further results will be presented.

Yang:JW Therapeutics: Current Employment. Liu:JW Therapeutics: Current Employment. Gu:JW Therapeutics: Current Employment. Zhou:JW Therapeutics: Current Employment. Tian:JW Therapeutics: Current Employment.