Data from China showed relma-cel yielded durable responses in patients with relapsed/refractory mantle cell lymphoma.
Treatment with the anti-CD19 CAR T-cell therapy relmacabtagene autoleucel (relma-cel; Carteyva) led to durable responses in patients with relapsed/refractory mantle cell lymphoma (MCL), according to data from a phase 2 trial (NCT04718883) conducted in China.1
Findings published in Blood Advances demonstrated that evaluable patients with at least 6 months of follow-up (n = 59) achieved a 3-month overall response rate (ORR) of 71.2% (95% CI, 57.92%-82.24%) per investigator assessment. Notably, the 3-month ORR was 71.19% per independent review committee (IRC) assessment, including a 3-month complete response (CR) rate of 54.2%. The investigator-assessed CR rates at 3 and 6 months were 59.3% and 49.2%, respectively.
The investigator-assessed median time to first response was 0.95 months. The median duration of response (DOR) was 18.1 months, and patients experienced a median progression-free survival (PFS) of 15.5 months. The 6-month DOR and PFS rates were 72.4% and 71.3%, respectively, per investigator assessment. The median overall survival (OS) was 19.5 months, and the 6- and 12-month OS rates were 82.8% and 68.9%, respectively.
“This phase 2 trial demonstrated that relma-cel is an effective and safety manageable therapy for patients with relapsed/refractory MCL, including those who have [progressed on prior] BTK [Bruton tyrosine kinase] inhibitor therapy,” lead study author Yan Xie, MD, of the Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), at Peking University Cancer Hospital and Institute in Beijing, China, and colleagues wrote in the publication. “The high durable response rates observed in our study could contribute to a potential shift in the treatment paradigm for relapsed/refractory MCL in China. These results warrant further development and integration of relma-cel in relapsed/refractory MCL treatment.”
Relma-cel is currently approved in China for the treatment of adult patients with relapsed/refractory large B-cell lymphoma after 2 or more lines of systemic therapy; adult patients with follicular lymphoma that is refractory or that relapses within 24 months of second-line or later systemic treatment; and adult patients with relapsed/refractory MCL after 2 or more lines of systemic therapy, including BTK inhibitors.2 The approval in MCL was supported by data from the phase 2 study published in Blood Advances.
The open-label, multicenter study enrolled patients at least 18 years of age with pathologically confirmed MCL.1 Patients needed to have relapsed/refractory disease following at least 2 prior lines of therapy that included anti-CD20 monoclonal antibodies, anthracycline- or bendamustine-containing chemotherapy, and BTK inhibitors. Other key inclusion criteria included measurable disease, an ECOG performance status of 0 or 1, an absolute lymphocyte count of at least 0.1 x 103 cells/µL, and a platelet count of at least 75 x 103 cells/µL.
All enrolled patients underwent leukapheresis for the manufacturing of relma-cel. Prior to the infusion of the chimeric antigen receptor (CAR) T-cell therapy, patients received lymphodepleting chemotherapy consisting of fludarabine at 25 mg/m2 per day and cyclophosphamide at 250 mg/m2 per day for 3 consecutive days. Relma-cel was then administered on day 1 at a target dose of 100 x 106 CAR T cells, with lymphodepletion completed within 2 to 7 days of receiving CAR T-cell therapy.
Investigator-assessed ORR at 3 months served as the trial’s primary end point. Secondary end points included investigator- and IRC-assessed ORR at other time points, DOR, PFS, time to response, OS, safety, and pharmacokinetics/pharmacodynamics.
Among 96 screened patients, 70 were enrolled and underwent leukapheresis. The study lost 9 patients prior to lymphodepletion due to patient withdrawal (n = 3), investigator decision (n = 2), adverse effects (AEs; n = 1), death (n = 1), loss to follow-up (n = 1), and other (n = 1). Notably, 40 of the 70 enrolled patients also received bridging chemotherapy. Of the 61 patients who underwent lymphodepletion, 59 received relma-cel; the CAR T-cell therapy was not administered to 2 patients due to patient withdrawal (n = 1) and investigator decision (n = 1).
In the 59 patients who received the CAR T-cell therapy, the median age was 59.0 years (range, 34-75), 32.2% were at least 65 years of age, and 79.7% were male. Additionally, the majority of patients had an ECOG performance status of at least 1 (59.3%), refractory disease (54.2%), and BTK inhibitor–relapsed disease (52.5%). Additionally, 13.6% had received prior autologous stem cell transplant. Patients had received either 1 (1.7%), 2 (28.8%), 3 to 4 (40.7%), or 5 or more (28.8%) prior lines of therapy.
MCL subtypes included classic (20.3%), blastoid (25.4%), pleomorphic (10.2%), and unknown (44.1%). Most patients (69.5%) had bulky disease measuring less than 5 cm. MCL International Prognostic Index scores included 0 to 3 (47.5%), 4 to 5 (35.6%), and 6 to 11 (16.9%). Most patients (59.3%) had extranodal lesions. Additionally, 37.3% had bone marrow involvement, 49.2% had spleen involvement, and 11.9% had gastrointestinal involvement.
Findings showed that treatment-emergent AEs (TEAEs) of any grade occurred in all patients who received relma-cel, including 94.9% who experienced grade 3 or higher TEAEs. The most frequently reported any-grade TEAEs included neutropenia (96.6%), leukopenia (88.1%), cytokine release syndrome (CRS; 81.4%), anemia (76.3%), and thrombocytopenia (74.6%). At grade 3 or higher, the most common TEAEs were neutropenia (76.3%), leukopenia (69.5%), lymphopenia (47.5%), and thrombocytopenia (39.0%).
Any-grade serious TEAEs were reported in 52.5% of patients. In 21 patients with serious TEAEs after CAR T-cell therapy infusion, 15 experienced serious treatment-related TEAEs.
Most instances of CRS were grade 1 or 2 (74.5%), and grade 3 CRS occurred in 6.8% of patients.
Among the 23 patients to die as of data cutoff, 12 deaths were attributed to disease progression, including 1 specifically due to cachexia. COVID-19 or complications related to the infection led to death in 5 patients, who were all in ongoing remission. Pneumonia was listed as the cause of death in 4 patients, including 2 where death was deemed likely to be related to the CAR T-cell therapy. The 12-month nonrelapse mortality (NRM) rate was 14.5%; when adjusted for COVID-19–related deaths, the 12-month NRM rate was 6.8%.
