Gender Disparities and Other DLBCL Developments

Tahir Latif, MD

Men may have a lower rate of survival among patients with diffuse large B-cell lymphoma (DLBCL), according to a recent study lead by University of Cincinnati researchers.

The study, which looked at 122 patients with DLBCL who had received R-CHOP, found that relative risk of death for male patients aged ≥60 years was about 1.19 times above females in the same age group.

Mortality rates for males with DLBCL who had received R-CHOP were 26.67% versus 19.05% for females (P <.0001). In male patients, mortality was significantly higher at 41.86% (±2.4) for patients aged ≥60 years, whereas in those aged ≤60 years, the mortality was 16.53% (±0.71; P <.0001). Similarly, among female patients, mortality was 35.12% (±3.31) in patients aged ≥60 years compared with 5.04% (±1.58) in patients aged ≤60 years (P <.0001).

For additional insight on these results and other developments in DLBCL, OncLive spoke with lead study author Tahir Latif, MD, associate professor of Medicine, interim chief, Division of Hematology Oncology, director, Infusion Services University of Cincinnati Cancer Institute.

OncLive: Were these findings surprising?

Dr Latif: When we examined mortality rates in patients with DLBCL, we knew that age was an important factor in predicting mortality. However, we were very surprised to discover that sex was also an important factor.

What are some possible reasons for this disparity?

It may be because we are not providing enough rituximab to male patients. The way we dose rituximab is based on body surface area and males may not be getting enough of it compared to females. Males may also metabolize the drug much quicker or simply require a higher dose for other reasons.

That is an area of interest for us and there is a further investigation ongoing to try and determine the cause of that disparity. We need to figure out what causes it so that we can take proactive steps to fix it. It is a challenge that we are working hard to overcome.

What are some of the other challenges in treating DLBCL?

Although DLBCL is classified as one disease, it really is not one disease. We have multiple subgroups, and recognizing which patients fit into which subgroups is essential to providing them with the proper treatment. This is one of the biggest challenges in DLBCL. There are ways of predicting which patients will or will not do well on specific treatments, both traditionally and, more recently, genetically and molecularly. It is important to give the most effective treatment upfront, as treating relapsed DLBCL is extremely difficult.

Are there any novel therapies on the horizon for treating patients with relapsed DLBCL?

It is a very exciting time for this particular disease. We are finally starting to understand the molecular mechanisms of how this cancer develops. This has allowed us to create several new targeted therapies that will become part of our traditional chemotherapy regimen. R-CHOP was the standard of care for this disease for decades. In the last 3 to 5 years, we have really seen some breakthroughs in this disease. In the next 3 to 5 years, I think we will get a better understanding on how to best use these new targeted therapies.

With these new targeted agents available, how do you see R-CHOP fitting into the treatment plan of this disease going forward?

For DLBCL, there will always be a role for R-CHOP because you do need to cut down the large volume of disease that most of these patients present with. However, I do think the role of R-CHOP will become much more limited. I think we will learn to use just the right amount. Instead of using 6 or 8 cycles of therapy, in the future we may only use a couple of cycles of R-CHOP therapy and, instead, combine it with these targeted therapies.

What is the best sequencing of these new agents?

It is too early to determine the best sequence because we are mainly using them for patients who have relapsed and really need them. However, in time, I think we will start to have a better understanding of when and where to use them. This is going to take some time.

Within DLBCL, are there any particular studies on the horizon that you are excited about?

Immunotherapy is very exciting in almost every area of oncology. We are very excited to see how those agents would work within lymphoma.

Yellu M, Guha G, Deeb A, et al. Gender specific mortality in diffuse large B cell lymphoma patients receiving R-CHOP. J Clin Oncol. 2015;33 (suppl; abstr e19523).