Anito-Cel Demonstrates Safety and Early Efficacy in R/R Multiple Myeloma

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Anitocabtagene autoleucel (anito-cel) produced durable responses and displayed a manageable safety profile in patients with relapsed/refractory multiple myeloma who received at least 3 prior lines of therapy or had triple-refractory disease, according to results from a first-in-human phase 1 study (NCT04155749) presented at the 2024 ASH Annual Meeting.

At a median follow-up of 38.1 months, no delayed or non–immune effector cell–neurotoxicity syndrome (ICANS) neurotoxicities were observed, including no cases of Parkinsonism, cranial nerve palsies, or Guillain-Barré syndrome. One patient experienced a grade 5 adverse effect (AE) of cardiac arrest post-study treatment, which was determined to be unrelated to the study drug and attributed to a non-study drug overdose.

Hematologic secondary primary malignancies—specifically myelodysplastic syndrome (MDS)—were reported in 3 patients. These were determined to be unrelated AEs associated with disease progression in individuals heavily pretreated with agents known to be linked to MDS. No secondary primary malignancies directly related to treatment were observed.

Early efficacy findings demonstrated that treated patients (n = 38) achieved an overall response rate (ORR) of 100%; 79% achieved a complete response (CR) or stringent CR (sCR). Additionally, 13% of patients experienced a very good partial response (VGPR), and 8% had a PR. Among evaluable patients (n = 28), 89% achieved minimal residual disease (MRD) negativity at a sensitivity threshold of 10⁻⁵.

“These results position anito-cel as a favorable treatment option for relapsed/refractory multiple myeloma, including high-risk patient subgroups, with promising safety and efficacy outcomes,” lead study author, Michael R. Bishop, MD, said in an interview with OncLive^®.

Bishop serves as director of the Hematopoietic Stem Cell Transplantation Program at the University of Chicago in Illinois.

Study Design

The phase 1 study enrolled patients with relapsed/refractory multiple myeloma who had received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, or those with triple-refractory disease following treatment with these 3 classes of agents.

Eligible patients needed to have measurable disease. Additional inclusion criteria included an ECOG performance status of 0 or 1 and adequate organ function.

Patients underwent apheresis fto collect cells used in the manufacturing of anito-cel. Following lymphodepleting chemotherapy with cyclophosphamide at 300 mg/m² and fludarabine at 30 mg/m² administered on days –5, –4, and –3, anito-cel was infused on day 0. Dose escalation was performed at 2 levels: dose level 1 consisted of 100 ± 20% × 10⁶ CAR T cells (n = 32), and dose level 2 involved 300 ± 20% × 10⁶ CAR T cells (n = 6). An expansion cohort was enrolled at dose level 1. Optional bridging therapy was allowed for patients prior to lymphodepletion.

The primary objectives of the study were to evaluate the incidence of treatment-emergent AEs (TEAEs), dose-limiting toxicities, and to establish the recommended phase 2 dose. Secondary end points included best overall response and ORR, assessed per the International Myeloma Working Group (IMWG) criteria. Exploratory endpoints included MRD negativity, duration of response (DOR), progression-free survival (PFS), and overall survival.

Patient and Disease Characteristics

At the data cutoff of October 3, 2024, 40 patients with relapsed/refractory multiple myeloma were enrolled in the study, and 38 received at least one dose of anito-cel. All 40 patients underwent leukapheresis and successful manufacture of the CAR T product, and 39 received lymphodepleting chemotherapy. The 38 dosed patients formed the efficacy and safety population.

The median age of the study population was 66 years (range, 44-76). Over half of the patients (53%) were 65 years of age or older. The majority of participants were male (61%), and most patients identified as White (84%), followed by Black/African American (11%) and Asian (3%).

Patients in the study were heavily pretreated with a median of 5 prior lines of therapy (range, 3-16). All patients were triple refractory, and 68% were penta refractory. High-risk prognostic features were present in 68% of patients, including 63% in the dose-level cohort and 100% in the dose-level 2 cohort. The median time since diagnosis was 6.5 years (range, 1.5-14.9 years).

Additionally, 76% of patients had undergone prior autologous stem cell transplantation, and 68% received bridging therapy prior to anito-cel infusion.

Additional Efficacy and Safety Findings

The median time to first response was 1.0 months (range, 0.9-1.9), and the median time to best response and CR/sCR was 2.8 months (range, 0.9-19.4) for each. MRD negativity was achieved at a median of 1.0 months (range, 0.9-5.6). The median duration of response was 29.1 months (95% CI, 15.8-38.0); 39% of patients had ongoing responses at data cutoff.

The median PFS for all patients was 30.2 months (95% CI, 16.6-NE)and the median PFS for patients who achieved a CR/sCR was 34.3 months (95% CI, 24.2-NE).

The 12-month PFS rate was 75.9% (95% CI, 58.7%-86.6%), and the 24- and 30-month PFS rates were 56.6% (95% CI, 39.2%-70.8%) and 50.3% (95% CI, 33.0%-65.3%), respectively.

“This is a phase 1 study of a relatively limited number of patients, but to see this response and to see these response rates and ongoing PFS is pretty impressive," Bishop said.

At least one serious AE) was reported in 5.3% of patients. Grade 3 or higher AEs occurred in 86.8% of patients. The most common grade 3/4 hematologic AEs included neutropenia (86.8%), thrombocytopenia (44.7%), and anemia (55.3%). Non-hematologic grade 3/4 AEs were less frequent and included hypertension (7.9%), pneumonia (7.9%), and elevated aspartate aminotransferase levels (5.3%).

“[This drug was] efficacious and highly safe in this phase 1 study, and again, the primary end point was safety, and the safety profile is actually very impressive for this drug,” Bishop explained.

Cytokine release syndrome (CRS) was observed in 95% of patients at grade 1 (47%), grade 2 (47%), and grade 3 (3%). No grade 4 or 5 CRS was reported. The median onset of CRS was 2 days (range, 1-12), and the median duration was 5 days (range, 1-9).

ICANS occurred in 18% of patients at grade 1 (9%), grade 2 (6%), and grade 3 (3%). No grade 4 or 5 ICANS was reported. The median onset of ICANS was 4.5 days (range, 3-6), and the median duration was 3.5 days (range, 1-9).

AEs led to treatment discontinuation in 2 patients (5.3%), including 1 case of infection and 1 of hypoxia/heart failure. Tocilizumab and dexamethasone were used to manage CRS in 84% and 58% of patients, respectively.

Reference

Bishop MR, Rosenblatt J, Binod Dhakal, et al. Phase 1 study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory multiple myeloma (RRMM): efficacy and safety with 34-month median follow-up. Blood. 2024;144(supp 1):4825. doi:10.1182/blood-2024-201080

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