A study exploring the potential use of chronotherapy to treat hematologic malignancies found that female patients with diffuse large B-cell lymphoma (DLBCL) experience better outcomes when receiving chemotherapy in the afternoon compared with the morning. These study results were published in JCI Insight.

Chronotherapy is the administration of medications at specific times to optimize efficacy and minimize adverse effects.

In this study, 2 cohorts of patients with diffuse large B-cell lymphoma (DLBCL) who were undergoing chemotherapy were analyzed to determine the effects of timing on survival (210 patients) and adverse events (129 patients).

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Patients were receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on either a morning or afternoon schedule (subcohorts of morning group [MG] and afternoon group [AG], respectively).

In the survival cohort, female patients in the MG seemed to experience more trouble, including more frequent disease progression, than did female patients in the AG (33.3% vs 13.9%). Significantly shorter progression-free survival (PFS) was noted for the female patients in the MG. Additionally, more deaths occurred among female patients in the MG compared with the AG (19.6% vs. 2.8%). Disease progression was the most common cause of those deaths.

In the adverse event cohort, the relative dose intensity (RDI) of cyclophosphamide, doxorubicin, and rituximab decreased in female patients in the MG compared with those in the AG; but no statistically significant difference was noted between male patients in the MG compared with those in the AG.

“One of the most prominent findings of our study is that female patients with DLBCL receiving R-CHOP in the morning more often experienced significant reduction of [dose intensity] leading to compromised survival mainly due to infection and neutropenic fever,” the researchers wrote.

The research team acknowledged that there was an imbalanced sex ratio between the morning and afternoon groups in the survival cohort, and future trials might focus on addressing unresolved issues around social factors that might have played a role.

“All in all, we explored the possibility of implementing sex-oriented chronotherapy as an alternative axis of augmenting DLBCL frontline therapy,” they wrote. “We conclude that female patients should, if possible, avoid receiving R-CHOP in the morning for optimal chemotherapy delivery with maximum response.”

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Kim DW, Byun JM, Lee JO, Kim JK, Koh Y. Chemotherapy delivery time affects treatment outcomes of female patients with diffuse large B cell lymphoma. JCI Insight. 2023;8(2):e164767. doi.org/10.1172/jci.insight.164767