“It’s very small numbers of patients, and we would not want to attempt to draw  definitive conclusions, but it’s consistent with other lines of evidence to suggest that ibrutinib may modulate T-cell phenotypes and function,” primary study author Mark Geyer, MD, hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, New York, told Cancer Therapy Advisor. He stressed that the analysis of ibrutinib-exposed patients was intended to be hypothesis generating. 

“The data [are] very limited,” echoed Dr Ramos. He encouraged further study of the addition of ibrutinib to CAR-T in clinical trials, noting that “there is a biological rationale behind why ibrutinib might be helpful in this particular setting.”

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Clinical trials are currently under way to evaluate the addition of ibrutinib to CAR-T in CLL and have initially reported high response rates.3,4 In particular, a single-arm pilot trial at the University of Pennsylvania (ClinicalTrials.gov Identifier: NCT02640209) is evaluating anti-CD19 CAR-T therapy among patients who were treated with ibrutinib first for 6 months.3 In addition, a phase 1/2 trial at Fred Hutch/University of Washington Cancer Consortium (ClinicalTrials.gov Identifier: NCT01865617) is evaluating JCAR014 therapy among CLL patients who received ibrutinib before infusion and continued ibrutinib for at least 3 months afterwards.4

“It certainly makes sense to test [adding ibrutinib] because if you can make the responses better, that certainly should be a goal, because toxicities are seemingly not so severe,” said Dr Siddiqi, while also cautioning that the patient numbers are still small. She complimented the Fred Hutchinson trial design for including a stopping point for ibrutinib, given that it is an expensive drug.

“We’re still kind of on the ground floor for CAR-T cell therapy in CLL,” said Dr Geyer. “Even though some of this is promising for sure, we do have a long way to go to overcome the limitations of the therapy.”

References

  1. Porter DL, Hwang WT, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7(303):303ra139.
  2. Geyer MB, Rivière I, Sénéchal B, et al. Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed/refractory CLL. JCI Insight. 2019;4(9):e122627.
  3. Gill SI, Vides V, Frey NV, et al. Prospective clinical trial of anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia shows a high response rate. Presented at: 2018 American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, California. Abstract 298.
  4. Gauthier J, Hiramaya AV, Hay KA, et al. Comparison of efficacy and toxicity of CD19-specific chimeric antigen receptor T-cells alone or in combination with ibrutinib for relapsed and/or refractory CLL. Presented at: 2018 American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, California. Abstract 299.