A New Hope? Selinexor Shines for Elderly DLBCL Patients in Real-World Study

Hey there! Let’s chat about something really important in the world of cancer treatment, specifically for our older population. We’re talking about Diffuse Large B-cell Lymphoma, or DLBCL. It’s a pretty common type of non-Hodgkin lymphoma, and while treatments have gotten way better over the years, it can still be a tough battle, especially for folks who are getting on in years. Treating elderly patients with DLBCL comes with its own set of challenges – they often have other health issues, might not tolerate intense chemotherapy as well, and the disease itself can behave a bit differently in them.

For a long time, the standard go-to treatment has been something called R-CHOP. And don’t get me wrong, R-CHOP is fantastic and has cured many people. But for some elderly patients, especially those who are a bit more frail or have significant comorbidities, R-CHOP or even a reduced-dose version like R-miniCHOP, might not be the best fit or might come with too many side effects. That’s why researchers are always looking for new, kinder, yet still effective options.

Enter Selinexor: A Different Approach

This is where a drug called selinexor comes into the picture. Now, selinexor isn’t your typical chemotherapy. It works in a really interesting way by targeting a protein called XPO1. Think of XPO1 as a kind of gatekeeper in the cell’s nucleus, responsible for exporting certain proteins out. Some of these proteins are actually tumor suppressors – the good guys that help keep cancer in check. Cancer cells often have too much XPO1, meaning they’re kicking those tumor suppressors out of the nucleus where they need to be to do their job. Selinexor basically jams this gate, keeping the tumor suppressors inside the nucleus where they can get back to work fighting the cancer. It’s already been approved for some specific types of relapsed or refractory (R/R) lymphomas and multiple myeloma, but what about using it *first-line* for elderly DLBCL patients?

Taking a Look at the Real World

That’s exactly what a group of researchers at Sun Yat-sen University Cancer Center wanted to find out. They conducted what’s called a “real-world study.” This means they looked back at the data from actual patients treated in their clinic, rather than a strictly controlled clinical trial. It gives us a peek into how these treatments perform in everyday practice, with all the complexities that come with real patients.

They focused on 16 elderly patients (aged 60 to 80, with a median age of 70.5) who received selinexor-based regimens as their very first treatment for DLBCL between late 2021 and late 2023. These weren’t necessarily the easiest cases either; many had high-risk features like advanced stage disease or high IPI scores. The patients received selinexor either combined with chemotherapy (like R-CHOP or R-miniCHOP) or, importantly, in chemotherapy-free combinations (like selinexor with rituximab and lenalidomide, or rituximab and orelabrutinib). The choice of regimen was based on the doctor’s assessment of the patient’s overall health, including comorbidities and frailty.

Hitting the Target: Efficacy Results

So, what did they find? Honestly, the results were pretty encouraging, especially considering this was a real-world setting with elderly patients. The primary goal was to see how many patients responded to the treatment (Objective Response Rate or ORR). And wow, the ORR was a fantastic 93.8%! Even better, 81.3% of the patients achieved a complete response (CR), meaning the signs of cancer disappeared. Another 12.5% had a partial response (PR), and only one patient had progressive disease.

What really caught my eye was the performance of the chemotherapy-free regimens. All five patients who received selinexor without traditional chemo achieved a complete response (100% CR)! That’s a big deal, especially for patients who might not be able to handle chemotherapy due to other health issues. And get this – all three patients in the study who were 75 years or older also achieved a complete response (100% CR). It suggests this approach could be particularly valuable for the oldest and potentially most vulnerable patients.

They also looked at how long patients stayed free from progression (Progression-Free Survival or PFS) and how long their response lasted (Duration of Response or DOR). With a median follow-up of 8.5 months, the median PFS hadn’t even been reached yet, and the estimated 1-year PFS rate was a solid 79.6%. Most patients (81.3%) kept their response for at least 6 months, and a quarter of them maintained it for at least a year.

Keeping it Safe: The Lowdown on Side Effects

Of course, with any cancer treatment, safety is just as important as efficacy, especially in elderly patients. The study also tracked adverse events (AEs), or side effects. Like many cancer treatments, selinexor-based regimens did cause some side effects, but they seemed manageable in this group.

The most common side effects were related to blood counts (haematologic AEs):

• Leukopenia (low white blood cells): 93.8% of patients
• Neutropenia (a specific type of low white blood cell): 81.3%
• Anaemia (low red blood cells): 50.0%
• Thrombocytopenia (low platelets): 25.0%

While these numbers seem high, most of these were less severe (Grade 1 or 2). Grade 3/4 haematologic AEs did occur in some patients, but they weren’t super common, and importantly, there were no fatal outcomes from things like febrile neutropenia (fever with low white counts), which can be a serious concern. Standard supportive care, like growth factors and antibiotics, helped manage these issues.

Non-haematologic side effects were also reported, with the most frequent being:

• Nausea and vomiting: 37.5%
• Fatigue: 31.3%
• Decreased appetite: 31.3%

Again, these were mostly mild to moderate (Grade 1 or 2) and improved with supportive care. There were a couple of specific cases mentioned – one patient developed a pulmonary infection that improved with antibiotics and a selinexor dose adjustment, and another had acute heart failure that recovered with treatment. Crucially, none of the 16 patients in this study had to stop treatment entirely because of toxicity, which is a really positive sign compared to some other studies in this population.

Where Does This Fit In?

This study is pretty significant because it’s one of the first real-world looks at using selinexor-based regimens as a *first-line* treatment specifically for elderly DLBCL patients. We know that standard R-CHOP can be tough, and while R-miniCHOP is an option, there’s definitely room for improvement in efficacy and tolerance, especially for frail patients or those with contraindications to chemotherapy.

Other studies have explored chemo-free options like R2 (rituximab and lenalidomide) or combinations including ibrutinib for frail elderly patients, showing feasibility but sometimes with lower response rates or challenges with toxicity in older age groups (as seen with ibrutinib in the PHOENIX study for older patients). The high response rates seen with selinexor, particularly the 100% CR rate in the chemo-free group in this study, are really exciting and suggest selinexor could be a powerful addition or alternative, especially when combined with other targeted agents.

The fact that selinexor works by a different mechanism (XPO1 inhibition) and seems to synergize with chemotherapy and other targeted drugs like BTK inhibitors makes it a promising candidate for combination therapies. For elderly patients with multiple comorbidities, having effective chemo-free options is a game-changer, allowing for personalized treatment plans that balance efficacy with the ability to tolerate the regimen.

Okay, But What Are the Catches?

As with any study, it’s important to look at the limitations. This was a retrospective study, meaning they looked back at existing data, which can sometimes have limitations compared to a prospectively designed trial. The sample size was also quite small – only 16 patients. While the results are impressive, they need to be confirmed in larger studies. Also, the follow-up time was relatively short (median 8.5 months), so we need longer follow-up to really understand the long-term survival benefits.

However, real-world studies like this are incredibly valuable because they include patients who might be excluded from strict clinical trials due to their age or comorbidities. So, while small, this study gives us a glimpse into how selinexor-based regimens might perform in the very patients who need new options the most.

Wrapping It Up

Treating elderly patients with DLBCL remains a complex challenge. Finding treatments that are both highly effective and well-tolerated is crucial. Based on this real-world study, selinexor-based regimens, including chemotherapy-free combinations, show really promising efficacy with a manageable safety profile as first-line treatments for this population. The high complete response rates, especially in the oldest patients and those receiving chemo-free options, are particularly noteworthy.

While we definitely need larger studies and longer follow-up to solidify these findings, this research provides exciting evidence that selinexor could become an important part of our toolkit for treating elderly patients with DLBCL, offering a potentially less toxic yet highly effective path forward. It underscores the importance of personalized treatment approaches for our older patients, considering their unique health profiles and treatment goals.

Source: Springer