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Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease. In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival. A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%). A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).

Patients with resectable lung cancer were assigned to neoadjuvant pembrolizumab or placebo plus chemotherapy and adjuvant pembrolizumab or placebo. Two-year event-free survival was 62.4% with pembrolizumab and 40.6% with placebo.

Patients with resectable non–small-cell lung cancer had a greater response and longer event-free survival with preoperative durvalumab plus chemotherapy and adjuvant durvalumab than with chemotherapy alone.

Osteosarcoma, which is most common in people 10 to 30 years of age, is generally treated with resection and adjuvant chemotherapy. Detection of gene rearrangements, copy-number variations, and targeted disruption of tumor suppressors by whole-genome sequencing has not yet led to improved treatment.

In this audio interview, Editor-in-Chief Eric Rubin and NEJM Evidence Associate Editor Oladapo Yeku discuss research being presented at the 2024 European Society of Medical Oncology annual meeting. . . .

In this audio interview, Editor-in-Chief Eric Rubin and NEJM Evidence Associate Editor Oladapo Yeku discuss research being presented at the 2024 European Society of Medical Oncology annual meeting. . . .

In this trial, omission of radiotherapy after breast-conserving surgery led to an increased incidence of local recurrence but no difference in distant recurrence as the first event or breast cancer–specific or overall survival.

Adagrasib produced responses in 43% of previously treated patients with non–small-cell lung cancer containing a KRAS G12C mutation, with median overall survival of 12.6 months. Regressions of stable brain metastases were noted in one third of evaluable patients. Gastrointestinal toxic effects dominated the adverse events, but fewer than 7% of patients stopped therapy.

A study involving 38 patients who initially had a response to adagrasib or who had a long period of stable disease in response to the drug but then had progression yielded diverse mechanisms of acquired resistance in 45% of them. Unlike resistance to the tyrosine kinase inhibitors, the cancer cell uses many mechanisms to overcome the inhibition of KRAS.