Time to treatment is an independent prognostic factor in aggressive non‐Hodgkin lymphomas

Abstract

In aggressive lymphomas, discrepancies in survival reported from experimental and observational studies may reflect selective non-enrolment of high-risk patients in trials. We examined the association between time from diagnosis to chemotherapy and overall survival in diffuse large B-cell (DLBCL), Burkitt (BL), mantle cell (MCL) and peripheral T-cell lymphoma (PTCL), using National Cancer Data Base records of 130 549 patients treated in 2004-2014. Across the histologies, patients who started chemotherapy within 7 days of diagnosis had more often high International Prognostic Index (IPI) or advanced-stage disease. The discrepancy in 3-year survival between groups treated within 7 or >30 days from diagnosis ranged from 14% in BL to 30% in MCL. After adjusting for the IPI, time to treatment was significantly associated with shorter overall survival. Using the group treated >30 days from diagnosis as reference, patients treated within 7 days had a hazard ratio of 1·38 [95% confidence interval (CI), 1·28-1·48] in DLBCL, 1·42 (95% CI, 1·22-1·66) in BL, 2·23 (95% CI, 1·79-2·78) in MCL and 1·46 (95% CI, 1·18-1·81) in PTCL. Time from diagnosis to treatment may reflect high-risk features uncaptured by standard prognostic assessments. Clinical trials should accommodate patients who need urgent therapy to improve external validity and detect treatment effects in high-risk groups.

Maternal and neonatal outcomes in 80 patients diagnosed with non‐Hodgkin lymphoma during pregnancy: results from the International Network of Cancer, Infertility and Pregnancy

“…Based on the non-pregnant population, DLBCL treatment should ideally not be delayed for >1 month in order not to impair survival. 23,24 As randomised controlled trials in pregnant women are ethically not possible, only observational studies are available. The available literature on rituximab during pregnancy, mainly based on case series of pregnant patients with autoimmune disease such as rheumatoid disease or multiple sclerosis, suggests reassuring obstetric and neonatal outcomes following second or third trimester exposure 6,13,25 However, rituximab should still be used with caution during pregnancy as the immunoglobulin receptor-mediated placental transfer increases with gestational age and potentially puts the fetus (and the mother) at risk of infections by B-cell depletion.…”

Outcomes of bendamustine‐ or cyclophosphamide‐based first‐line chemotherapy in older patients with indolent B‐cell lymphoma

“…Baseline health status was approximated by the National Cancer Institute Comorbidity Index, Davidoff's disability indicator (a validated measure of self‐reported performance status), record of chronic kidney disease, thromboembolism, or neuropathy, prior hospitalization or emergency department (ED) visit, and log‐transformed Medicare spending within 1 year before chemotherapy. Indicators of lymphoma severity included histologic subtype, stage, presence of B symptoms, anemia, and diagnosis‐to‐treatment interval, known to correlate with survival in lymphoma …”

Disparities in the enrollment to systemic therapy and survival for patients with multiple myeloma

“…Although the findings may appear paradoxical, the variability likely reflects the fact that sicker patients and patients with advanced stage MM associated with poor prognosis are enrolled into therapy earlier [44] . Therefore, it is proposed that clinical trials should accommodate patients who need urgent therapy to detect treatment effects in high‐risk groups [44] .…”

“…While timely initiation of therapy is an important factor to improve outcomes, it is interesting to note that in studies on hematological malignancies, there is paradoxically worse survival in those who started therapy earlier which is contradictory to that from solid tumors [44] , [45] . Although the findings may appear paradoxical, the variability likely reflects the fact that sicker patients and patients with advanced stage MM associated with poor prognosis are enrolled into therapy earlier [44] . Therefore, it is proposed that clinical trials should accommodate patients who need urgent therapy to detect treatment effects in high‐risk groups [44] .…”