On February 5, 2021, the Food and Drug Administration (FDA) approved lisocabtagene maraleucel (Breyanzi, Juno Therapeutics, Inc. or liso-cel) for the treatment of adults with relapsed or refractory (R/R) large B-cell lymphoma after two or more lines of systemic therapy.
Liso-cel (formerly known as JCAR-017) is a CD19-directed, defined composition, chimeric antigen receptor CAR- T cell immunotherapy with equal doses of CD8+ and CD4+ T cells that are genetically modified to produce a CAR protein that allows T cells to identify and eliminate CD19-expressing normal and malignant cells.
CD19 is found on nearly all normal and cancerous B cells including CLL cells and successful therapy leads to normal B cell depletion as well as elimination of the B cell cancer.
This approval was based on research on 192 patients with R/R large B-cell lymphoma that found that the overall response rate (ORR) was 73% with a complete response (CR) rate of 54%.
Cytokine release syndrome (CRS) occurred in 46% of patients (Grade 3 or higher, 4%) and neurologic toxicity occurred in 35% (Grade 3 or higher, 12%). Three patients died from neurologic toxicity.
This is a difficult cancer to treat. The results are encouraging and offer hope to patients who are short on options.
Why is this approval so important to the CLL community?
This approval bodes well for chronic lymphocytic leukemia (CLL) patients where liso-cel has demonstrated similar or even better results when combined with ibrutinib as outlined in ASH 2020: Dr. Bill Wierda on CAR-T liso-cel combined with ibrutinib for chronic lymphocytic leukemia (CLL). The numbers are much smaller in that trial but of the 19 patients evaluable for minimal residual disease (MRD), 17 (89%) achieved undetectable MRD (measurable residual disease) or uMRD in blood via flow cytometry and 15 (79%) in the bone marrow by next-generation sequencing (both sensitivity of ≤10-4). Over half the patients had a complete response (CR).
If these promising numbers hold as the trial expands (trial sites can be found here on ClinicalTrials.gov), CLL may be the next approval.
This present approval includes “including DLBCL arising from indolent lymphoma” otherwise known as Richter’s Transformation in CLL.
How and where CAR-T will ultimately fit into the CLL treatment paradigm is still in flux, but it is increasingly looking as though this option will be part of the treatment armamentarium.
And as of Feb. 5, 2021, it is already an option for Richter’s Transformation.
That is all good news for all chronic lymphocytic leukemia patients.
Here is the link to the FDA’s official press release: FDA Approves Lisocabtagene Maraleucel for Relapsed or Refractory Large B-Cell Lymphoma.
Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed
Co-Founder, Executive VP and Chief Medical Officer