Undetectable MRD Status in Patients With CLL

Laura Joszt

Achieving undetectable minimal residual disease (MRD) status is important for deep and durable responses in patients with chronic lymphocytic leukemia (CLL), according to 2 abstracts presented at the 2019 American Society of Clinical Oncology Annual Meeting.

One abstract analyzed the difference in outcomes in patients with CLL who had undetectable MRD versus those with detectable MRD.1 The researchers evaluated 11 studies comprising 2457 patients with CLL. These patients were treated upfront with chemotherapy or chemo-immunotherapy.

Undetectable MRD status was associated with longer progression-free survival in patients who achieved complete remission (CR). While overall survival (OS) was longer in patients who had undetectable MRD overall, it did not predict longer OS in patients who achieved CR, according to International Workshop on CLL guidelines.

According to the authors, the findings validate the importance of achieving undetectable MRD status in patients newly diagnosed with CLL.

“MRD status should be incorporated as endpoint into prospective clinical trials and in the evaluation of new agents for CLL therapy as already accepted by the European Medicines Agency,” they wrote.

In the second abstract, researchers assessed safety, pharmacokinetics, and efficacy of lisocabtagene maraleucel (liso-cel), an anti-CD19 chimeric antigen receptor T-cell therapy, in patients with CLL or small lymphocytic leukemia (SLL) who had received at least 2 lines of prior therapy.

A total of 16 patients had received liso-cel at data cutoff and 15 of the patients were evaluable. There was 1 dose-limiting toxicity of grade 4 hypertension. The most common grade 3 or 4 treatment-emergent adverse events were cytopenias; only 1 patient had grade 3 cytokine release syndrome and 3 patients had grade 3 neurological events.

The overall response rate was 87% (13/15 patients) and 7 patients (47%) achieved CR. Ten of the patients achieved undetectable MRD in blood and 7 patients in bone marrow. MRD-negative CR was seen in patients who had previously failed both Bruton’s tyrosine kinase inhibitors and venetoclax, the authors noted.

1. Molica S, Giannarelli D, Montserrat E. Minimal residual disease and survival outcomes in patients with chronic lymphocytic leukemia: a systematic review and meta-analysis. Presented at: 2019 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract E19003.
2. Siddiqi T, Dorritie KA, Drobnyk Soumerai J, et al. TRANSCEND CLL 004: minimal residual disease (MRD) negative responses after lisocabtagene maraleucel (liso-cel; JCAR017), a CD19-directed CAR T cell product, in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). Presented at: 2019 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 7501.
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