We are pleased to present highlights of the latest advances in immunotherapy emerging from the 2026 ASCO Annual Meeting, May 29, 2026.
(Thanks to Chinmay Jani, MD and Terri Holzen, PhD for compiling these scientific highlights)
Azer-cel, an allogeneic CAR T cell, for relapsed or refractory CD19+ B cell malignancies
7012. Safety and efficacy of Azer-cel, an allogeneic CD19 CAR T for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma and chronic lymphocytic leukemia not previously exposed to autologous CAR T therapy
Supriya Gupta (University of Minnesota, Minneapolis, MN, USA) reported results from a phase 1b trial of azer-cel in combination with low-dose subcutaneous interleukin 2 (IL-2) relapsed or refractory CD19+ B cell malignancies. Azer-cel is an allogeneic, CD19-directed, CAR T cell therapy derived from healthy donor T cells. The CD19-targeting CAR is inserted into the T-cell receptor alpha constant (TRAC) gene locus via the ARCUS gene editing platform. The CD19 CAR also includes a novel N6 costimulatory domain that enables signal transduction and promotes CAR T cell cytotoxicity and persistence. This report focused on the CAR T naïve patient population of the dose expansion phase of the trial. 25 CAR T naïve patients received lymphodepleting chemotherapy (Fludarabine 30 mg/m^2 x3 days, cyclophosphamide 750 mg/ m^2 x3 days) followed by azer-cel infusion and treatment with low-dose subcutaneous IL-2 (1 million IU, D1-14) to support CAR T cell expansion and activity. Diseases represented within the patient population included diffuse large B cell lymphoma (DLBCL; n=6), marginal zone lymphoma (MZL; n=6), chronic lymphocytic leukemia (CLL; n=4), primary central nervous system lymphoma (n=4), follicular lymphoma (n=3), primary mediastinal B cell lymphoma (n=1), and Waldenstrom’s macroglobulinemia (n=1). Median age of the patent population was 63 (56-69) with 18 (72%) males and 22 (88%) Non-Hispanic Whites. Patients had received a median of 2 prior lines of therapy (1-7), and 56% of patients had received prior treatment with BTK inhibitors. 96% of patients experienced treatment-emergent adverse events (TEAEs), and 84% of patients experienced TEAEs of grade 3 or higher. 21 patients (84%) experienced cytokine release syndrome (CRS), and all cases were grade 1 or 2. 10 patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS): 3 cases of ICANS were grade 3, and 1 case was grade 4. ICANS was more frequent in patients with DLBCL, with 4 of 6 patients with DLBCL experiencing ICANS, and 2 cases were grade 3 or higher. ICANS did not occur in any patients with CLL. Among the 24 evaluable patients, the objective response rate (ORR) was 79%, and responses occurred across all disease states. Among patients with indolent disease (n=14), the ORR was 93%. Responses occurred in 5 patients with MZL, with 4 patients achieving a complete response (CR) and 1 partial response (PR). All 4 CRs are ongoing, one patient is minimal residual disease (MRD) negative, and one patient is MRD positive but below the limit of detection. Reponses were also observed in all 4 patients with CLL, with 3 PRs (2 ongoing) and 1 ongoing CR. CAR T expansion was observed in the CAR-T naïve cohort, including patients with CLL and MZL. These allogeneic CD19-targeting CAR T cell azer-cel exhibited promising clinical activity across a range of B cell malignancies in CAR T- naïve patients, and a manageable safety profile, supporting further investigation. Of note, Molecular Residual Disease (MRD) trends were consistent with the anti-tumor activity if azer-cel. Enrollment in the CAR T naïve cohort is ongoing and a cohort testing the combination of azer-cel with a BTK inhibitor is being explored.
Early intervention with the T cell engager elranatamab for high-risk smoldering multiple myeloma
7500. Safety and efficacy of elranatamab as early intervention in patients with high-risk smoldering myeloma: First results from the phase 2 ERASMM (EMN34) study
Cyrille Touzeau (University Hospital of Nantes, Nantes, France) presented the efficacy and safety results of ERASMM, a phase 2 study of elranatamab, a BCMA x CD3 bispecific antibody for high-risk smoldering multiple myeloma (HR SMM). Elranatamab exhibits strong anti-tumor activity against relapsed/refractory multiple myeloma (RR MM), and although early intervention with lenalidomide or daratumumab in patients with HR SMM delays progression to active disease, deep responses occur at low rates, indicating an unmet need. 50 patients with previously untreated HR SMM received single agent elranatamab on a 28-day cycle for a fixed duration of 2 years. Treatment is ongoing in 43 patients, and treatment was discontinued in 7 patients. Median age was 65 (32-89) with median time from SMM diagnosis to study enrollment of 7 months (3-16) All patients met at least two of the “2/20/20” criteria (Bone Marrow Plasma Cells (BMPC) > 20%; FLC ratio > 20%; M-spike > 2 g/dl). No new safety signals were observed in patients with HR SMM compared to patients with RR MM. Five patients discontinued therapy due to adverse events. 22 patients (44%) experienced neutropenia, and 20 of those cases were grade 3 or 4. 35 patients (70%) experienced cytokine release syndrome (CRS), and all but 2 events were grade 1 or 2. Per protocol, 22 patients received pre-emptive tocilizumab. Grade 3 non-hematologic adverse events occurred at a low frequency, and no cases of ICANS were observed. Infections occurred in 27 patients (54%), 7 were grade 3. The rate of infections in ERASMM compared favorably to previous studies of elranatamab for RRMM, including lower rates of grade 3 infections and no grade 4 or 5 events. The complete response rate (CRR) deepened over time, increasing from 30% after 6 cycles of elranatamab to 72% at a median follow-up of 14 months. The objective response rates at these time points were 90% and 92%, respectively. 29 patients with a suspected complete response were evaluated for minimal residual disease (MRD), and 90% had undetectable MRD. At a median follow-up of 14 months, all patients are alive, and progression-free survival is 96%. No patients have progressed to active myeloma, and 2 patients have exhibited biochemical progression. Treatment is ongoing in 86% of patients. Although longer follow-up and larger patient populations are needed to further validate these results, these data support further investigation of single-agent elranatamab as an early intervention for high risk smoldering multiple myeloma. These data also support using T cell engagers for precancerous conditions or early-stage disease, when the immune system is still intact, potentially improving clinical efficacy and lowering the risk of infections and other adverse events.
ctDNA analyses from the KEYNOTE-564 study: Adjuvant pembrolizumab versus placebo for patients with renal cell carcinoma
4502. ctDNA analysis in participants with renal cell carcinoma treated with adjuvant pembrolizumab or placebo in the KEYNOTE-564 trial
Toni K. Choueiri (Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA) presented an analysis of pre-treatment and on-treatment circulating tumor DNA (ctDNA) and clinical outcomes from the KEYNOTE-564 trial. The KEYNOTE-564 trial established that adjuvant pembrolizumab was superior to placebo in patients with renal cell carcinoma (RCC) at increased risk of recurrence. Patient samples from both treatment groups were evaluated for ctDNA after surgery (baseline) and at cycle 5 day 1 (C5D1) of adjuvant pembrolizumab or placebo. 736 of the 994 patients in the KEYNOTE-564 study had ctDNA-evaluable samples at baseline. 5.4% were ctDNA positive using a tissue exome-based 16-plex ctDNA assay, and 8.2% were ctDNA positive with a 64-plex based assay, aligning with previous observations that RCC is associated with low rates of ctDNA shedding. In the pembrolizumab arm, median disease-free survival (DFS) was not reached in patients who were ctDNA negative at baseline and 10.1 months in patients who were ctDNA positive at baseline (p<0.0001). Similar results were observed in the placebo arm (median DFS 80.7 months and 6.4 months, respectively, p<0.0001), suggesting ctDNA positivity at baseline is associated with poor clinical outcomes, regardless of adjuvant treatment. DFS favored pembrolizumab over placebo regardless of baseline ctDNA status, indicating that pembrolizumab is associated with clinical benefits, even in patients who are ctDNA positive at baseline. ctDNA status at baseline indicated high specificity but low sensitivity to predict DFS. Using the exome-based 16-plex assay, positive predictive values were 95% and 81% for the pembrolizumab and placebo arms, respectively, and negative predictive values were 55% and 63% for the pembrolizumab and placebo arms, respectively. Similar values were observed with the 64-plex assay. Among the 10 patients in the pembrolizumab arm who were ctDNA positive at baseline with the 16-plex assay, 6 exhibited ctDNA clearance at C5D1 (ctDNA clearance rate 60%), compared with a ctDNA clearance rate of 21.4% (3/14) in the placebo arm , which is consistent with the DFS benefit of adjuvant pembrolizumab . This analysis indicates that following surgery for RCC, ctDNA exome-based testing yields low levels of ctDNA positivity and sensitivity at baseline, but ctDNA positivity is highly specific for disease recurrence. These data also indicate that pembrolizumab is associated with improved clinical outcomes regardless of ctDNA status. This study also highlights the limitations of exome-based ctDNA testing for certain cancers such as RCC and indicates that current exome-based ctDNA technology should not be used to identify patients with RCC who are at increased risk of recurrence and would benefit from adjuvant pembrolizumab.
To learn about other clinical trials of immune checkpoint inhibitors for renal cell carcinoma, see this paper from Viray et al in JITC.