Late noon chemotherapy reduces toxicity and improves survival in diffuse large B cell lymphoma patients

Chronotherapy is a drug intervention at specific times of the day to optimize efficacy and minimize adverse effects. Its value in hematologic malignancy remains to be explored, in particular in adult patients.

A new study by Dae Wook Kim and team showed that rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) medication given in the late afternoon to diffuse large B cell lymphoma (DLBCL) female patients can lessen toxicity while increasing effectiveness and survival rates.

The findings of the study have been published in The Journal of Clinical Investigation.  

Drugs are administered during specified times of the day during chronotherapy to maximize effectiveness and reduce side effects. Its use in hematologic malignancy is still being investigated, especially in patients who are adults. In order to determine if chronomodulated immunochemotherapy may be used to treat diffuse large B cell lymphoma (DLBCL), this study was conducted.

Chronotherapeutic analysis was done on two cohorts of diffuse large B cell lymphoma (DLBCL) patients who were receiving treatment on a dichotomized schedule (morning or afternoon). In a survival cohort (n = 210) and an adverse event cohort (n = 129), respectively, the impact of a morning or afternoon regimen of rituximab with doxorubicin, cyclophosphamide, vincristine, and prednisone (R-CHOP) on survival and medication tolerance was assessed. Analysis of circadian fluctuation in hematologic markers was performed on about 14,000 healthy people.

The key findings of this study were:

Female patients' progression-free survival (PFS) and overall survival (OS), but not male patients', were both noticeably reduced when chemotherapy was administered mostly in the morning. 

Female patients treated in the morning had lower dosage intensities (cyclophosphamide 10%; doxorubicin 8%; and rituximab 7%; P = 0.002, 0.002, and 0.003, respectively). This was mostly due to infection and neutropenic fever: those who were treated in the morning had a greater frequency of infections (16.7% vs. 2.4%), as well as febrile neutropenia (20.8% vs. 9.8%). 

The greater daily variability of circulating leukocytes and neutrophils in female patients than in male patients can be used to explain the sex-specific chronotherapeutic effects.

In conclusion, overall, this study investigated whether sex-oriented chronotherapy may be used as an alternate axis to supplement DLBCL frontline therapy. For the best administration of chemotherapy and the greatest response, female patients should, if at all possible, avoid having R-CHOP in the morning.

Reference: 

Kim, D. W., Byun, J. M., Lee, J.-O., Kim, J. K., & Koh, Y. (2023). Chemotherapy delivery time affects treatment outcomes of female patients with diffuse large B cell lymphoma. In JCI Insight (Vol. 8, Issue 2). American Society for Clinical Investigation. https://doi.org/10.1172/jci.insight.164767