Clonal hematopoiesis of indeterminate potential (CHIP) is associated with some outcomes of chimeric antigen receptor (CAR) T-cell therapy, according to research published in Blood Advances.
Researchers found that CHIP was associated with higher rates of complete response (CR) and cytokine release syndrome (CRS) in patients younger than 60 years, but there was no association between CHIP and survival, regardless of age.
The researchers explained that clonal hematopoiesis “describes an expansion of clonally derived hematopoietic cells in the peripheral blood,” and CHIP “is defined by the presence of leukemia-associated mutations with a variant allele fraction (VAF) of at least 2%.”
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Because CHIP is associated with poorer prognosis in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) who undergo autologous transplant, the researchers set out to determine if CHIP could influence outcomes in patients receiving CAR T-cell therapy.
The researchers conducted a single-center study of 154 patients who had received CAR T-cell therapy since 2016 and who had blood specimens available for genetic analysis.
There were 144 NHL patients who received anti-CD19 CAR T-cell therapy and 10 MM patients who received a CAR T-cell product targeting B-cell maturation antigen. The patients’ median age was 63 years (range, 24-83 years), and they had received a median of 4 lines of prior therapy (range, 1-10).
Clonal hematopoiesis (VAF ≥.004) was found in 76% of patients, and CHIP (VAF ≥.02) was found in 48%. Patients with clonal hematopoiesis had a median of 2 mutations. Most mutations occurred in PPM1D, DNMT3A, TP53, TET2, and SRCAP.
Overall, the CR rate was significantly higher in NHL patients with CHIP than in those without it — 77.6% and 57.9%, respectively (P <.0133). The same was true for NHL patients younger than 60 years of age — 88.9% and 46.7%, respectively (P =.0067) — but not for older patients — 73.5% and 66.7%, respectively (P =.64).
In NHL patients younger than 60 years, the rate of grade 2 or higher CRS was significantly higher in patients with CHIP than in those without it — 77.8% and 45.9%, respectively (P =.042).
However, there was no significant difference in the rate of grade 2 or higher CRS for NHL patients age 60 or older — 62.0% and 74.4%, respectively (P =.26) — or in the overall NHL cohort — 66.2% and 60.5%, respectively (P =.49).
A similar trend was observed when the MM patients were included in the CRS analysis, but the researchers did not report any other outcome data for the MM patients.
When the researchers assessed survival in the NHL cohort, they found no association between CHIP and progression-free survival (PFS) or overall survival (OS). The median PFS was 25.6 months in patients with CHIP and 21.5 months in patients without CHIP (P =.6). The median OS was not reached in either group (P =.6).
“Our data suggest that CHIP can influence CAR T-cell biology and clinical outcomes, but, in contrast to autologous transplantation, CHIP was not associated with worse survival and should not be a reason to exclude individuals from receiving this potentially life-prolonging treatment,” the researchers wrote.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Miller PG, Sperling AS, Brea EJ, et al. Clonal hematopoiesis in patients receiving chimeric antigen receptor T-cell therapy. Blood Adv. Published August 3, 2021. doi:10.1182/bloodadvances.2021004554
