Bhagirathbhai Dholaria

Summary Pre‐transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo‐HCT). The impact of MRD on the outcomes of post‐transplant cyclophosphamide (PTCy)‐based allo‐HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow‐up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% ( p = 0.99), and 10.6% and 6.8% ( p = 0.29), respectively, and 2‐year chronic GVHD was 35% and 30.4% ( p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia‐free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD‐free, relapse‐free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non‐relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo‐HCT with PTCy, pre‐transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.

Summary Chimeric antigen receptor (CAR) T‐cell (CAR‐T) therapy can provide durable remission in patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) after failure of chemoimmunotherapy. However, patients who are refractory or relapsing after CAR‐T therapy have poor outcomes. Multiple mechanisms of CAR‐T therapy failure have been proposed but management of these patients remains a challenge. As CAR‐T therapy moves earlier in the treatment of DLBCL, we urgently need trials focused on patients with relapse after CAR‐T therapy. Recent advances in novel immunotherapies such as bispecific antibodies, antibody–drug conjugates and next‐generation CAR‐T therapies may provide avenues for treatment. Here we review the available data on using these drugs after failure of CAR‐T therapy and provide a framework for the ideal sequencing of these novel agents.