PF295 POPULATION‐BASED STUDY ON DIFFERENT REGIMENS OF R‐CHOP IN PATIENTS WITH NEWLY DIAGNOSED DIFFUSE LARGE B‐CELL LYMPHOMA IN THE NETHERLANDS SUPPORTS THE USE OF 6 CYCLES OF R‐CHOP21
Authors: Issa D. , Dinmohamed A. , Wondergem M. , Blommestein H. , Lugtenburg P. , Visser O. , Zweegman S. , Chamuleau M. 
Published: June 2019

Background:

Randomized clinical trials (RCTs) showed similar efficacy between R‐CHOP14 and R‐CHOP21 regimens, and less toxicity with 6 v 8 cycles of R‐CHOP when applied as first‐line treatment among elderly (>60 years) DLBCL patients. Likewise, both 6x R‐CHOP14 plus two cycles of rituximab (2R) and 8x R‐CHOP21 result in comparable efficacy in patients 18–80 years. However, it is unknown whether the interval of 6x R‐CHOP can be extended to 21 days especially among younger patients with advanced‐stage DLBCL. Unfortunately, this question is unlikely to be addressed in future RCTs. In this regard, population‐based studies can lend support to address unanswered hypotheses.

Aims:

The aims of this population‐based study among newly diagnosed DLBCL patients were two‐fold. First, we sought to confirm results of RCTs on the effectiveness of R‐CHOP21 v R‐CHOP14, irrespective of the number of cycles (analysis A) and 6x v 8x R‐CHOP, irrespective of dose density (analysis B). Secondly, we specifically assessed in patients aged 18–64 years whether 6x R‐CHOP21 ± 2R is equally effective as other R‐CHOP regimens (analysis C).

Methods:

We selected all patients aged ≥18 years diagnosed with advanced‐stage DLBCL (stages II‐IV) between 2004–2010 from the Dutch Population‐based HAematological Registry for Observational Studies (PHAROS) and between 2014–2015 from the nationwide Netherlands Cancer Registry (NCR). Of note, the use of 2R after 6x R‐CHOP was not uniformly registered in PHAROS. The primary endpoint was overall survival (OS) in age groups: 18–64, 65–74, and ≥75 years. Multivariable evaluation of OS was applied using Cox regression to account for some imbalances between treatment groups.

Results:

The cohort for the first analysis included 2,338 patients who received ≥1 cycle of R‐CHOP, of whom 637 (27%) received R‐CHOP14 and 1,701 (73%) R‐CHOP21. Recipients of R‐CHOP21, as compared to recipients of R‐CHOP14, were older (median age, 68 v 61 yrs; P < 0.001) and more often had an IPI of ≥3 (47% v 38%; P < 0.001). After multivariable analysis, the adjusted risk of mortality was similar between recipients of R‐CHOP14 and R‐CHOP21 across all age groups (Fig 1A for patients <65 yrs). In addition, R‐CHOP14 was associated with more polyneuropathy, dose modifications and dose delays than R‐CHOP21. Response rates were similar in both groups. For the secondary analysis of 6 vs 8 cycles, 1,892 patients were included. Analysis showed that 6 and 8 cycles were equally effective in all age groups (Fig 1B for patients <65 yrs). Not all patients received 2R after 6 cycles, but documentation was not reliable enough to draw conclusions. 6xR‐CHOP21 ± 2R was equally effective when compared to all other regimens in all patients (Fig 1C for patients <65 yrs).

Summary/Conclusion:

Our population‐based analyses add support to the notion from several RCTs that R‐CHOP21 and R‐CHOP14, and 6x and 8x R‐CHOP are equally effective. Furthermore, 6x R‐CHOP21 ± 2R was found to be equally effective compared to all other regimens in all age groups. Therefore, 6xR‐CHOP21 ( ± 2R) should be considered the preferred first‐line regimen for all patients with advanced‐stage DLBCL. The question whether 2R after 6x CHOP21 can be omitted without compromising efficacy remains a topic for future studies.

image