Breaking Potential New Standard of Care for Relapsed/Refractory Follicular Lymphoma Patients

Background: Why This Study Matters

Follicular lymphoma (FL) is a slow-growing form of blood cancer that often relapses after treatment. Patients usually undergo multiple rounds of therapy as the follicular lymphoma returns. 

While there are successful common first-line treatments for follicular lymphoma, their effectiveness tends to decrease with each subsequent treatment. Immunotherapy has shown promise in treating relapsed or refractory follicular lymphoma, but there’s a need to improve the durability of these results.

A recent clinical trial, inMIND, explored whether adding a novel monoclonal antibody called tafasitamab (tafa), to a standard-of-care combination (lenalidomide [len] + rituximab [R]) could help patients with relapsed or refractory follicular lymphoma achieve better outcomes.

Laurie H. Sehn from the BC Cancer Centre in British Columbia presented the information as a late-breaking abstract at the 2024 American Society of Hematology (ASH) meeting. While this data was submitted to the ASH committee after the deadline, they still chose to release it, because it’s important enough to be shared immediately because it can shape the future of treatment for follicular lymphoma. 

What Was Studied?

The inMIND trial tested the addition of tafasitamab, a CD19-targeting monoclonal antibody, to the len+R combination in patients who had already undergone at least one prior treatment.

Trial Design

The trial was performed in 26 countries worldwide and consisted of two arms (or two groups). Both groups received the standard-of-care therapy of lenalidomide + rituximab, but only one arm received an additional IV therapy of tafasitamab. 

The other group received IV therapy as well, but it would be a placebo, meaning no medication would be found inside it. 

• 273 received the standard-of-care therapy plus the tafa, while 275 patients received the standard-of-care therapy plus placebo. 
• The median age of patients were 64, but 20% of patients were 75+ years old
• The median previous lines of therapy was 1, though a little less than half had 2 or more lines

Key Focus

The study primarily aimed to measure progression-free survival (PFS), which reflects how long patients live without their follicular lymphoma worsening.

Promising Results from the inMIND Trial

The results highlight significant benefits for patients receiving tafa + len+R compared to len+R alone.

Progression-Free Survival

The study found that adding tafasitamab (tafa) to the standard treatment combination of lenalidomide (len) + rituximab (R) significantly improved how long patients with follicular lymphoma (FL) stayed progression-free (the amount of time a patient lives without their cancer getting worse (progressing), returning (relapsing), or causing death):

• Patients receiving tafa + len+R lived 22.4 months on average without their cancer getting worse.
• Patients receiving placebo (pbo) + len+R lived 13.9 months progression-free on average.
• This means the combination with tafa gave patients about 8.5 additional months of progression-free time compared to len+R alone.

What Does "57% Lower Risk" Mean?

The study also showed that patients who received tafa were 57% less likely to experience cancer progression, relapse, or death during the study than those who received len+R without tafa. This percentage comes from a measure called the hazard ratio (HR):

• A hazard ratio (HR) of 0.43 means patients in the tafa group had a 43% chance of experiencing progression or death compared to the placebo group, making them 57% less likely to face these outcomes.
• The results had a P value of <0.0001, which means the results are very reliable, with an extremely low chance that they happened by coincidence.

Stronger Tumor Responses

Patients who received tafa + len+R had stronger tumor responses compared to those on len+R alone:

Complete Response Rate (CR):

• 49.4% with tafa: Nearly half of the patients receiving tafa had no detectable cancer after treatment.
• 39.8% with placebo: About 4 in 10 patients in the placebo group achieved this.
• What this means: Adding tafa increased the likelihood of fully eliminating detectable cancer.

Overall Response Rate (ORR):

• 83.5% with tafa: Over 8 in 10 patients showed significant tumor shrinkage or elimination.
• 72.4% with placebo: Around 7 in 10 patients in the placebo group achieved this.
• What this means: Adding tafa helped more patients see meaningful results.

Duration of Response (DOR):

• 21.2 months with tafa: Tumor shrinkage or elimination lasted nearly 2 years on average.
• 13.6 months with placebo: The response lasted just over a year without tafa.
• What this means: Patients on tafa had an average of 7.6 additional months before their cancer started growing again.

Time to Next Treatment (TTNT)

Time to Next Treatment (TTNT) measures how long a patient can go without needing another therapy after finishing their current one. This is important because longer TTNT means more time before having to deal with additional treatments and their potential side effects.

• With tafa + len+R:
  The median TTNT was not reached during the study. This means more than half of the patients in this group hadn’t yet needed another treatment when the study ended.
• With placebo + len+R:
  The median TTNT was 28.8 months, meaning that half of these patients required a new treatment within just over two years.

Safety Profile

Every treatment comes with the possibility of side effects, and it’s important to understand what to expect and how to manage them. In this study, the rates of severe side effects (called Grade 3 or 4 side effects) were similar for both groups of patients:

• 71% of patients treated with tafa + len+R experienced severe side effects.
• 69.5% of patients treated with placebo + len+R had similar issues.
• This means adding tafa did not significantly increase the overall likelihood of severe side effects. Though the difference between the two arms is not statistically significant, it's important to note that the patients on the tufa arm experienced a higher rate of side effects.

Some side effects were more common than others. Here’s what patients experienced most frequently:

Neutropenia (low white blood cell counts):

• Occurred in 40% of patients with tafa and 38% with placebo.
• Neutropenia can increase the risk of infections but is often managed with medications or treatment adjustments.

Pneumonia:

• Experienced by 8% with tafa and 5% with placebo.
• This condition can range from mild to severe, requiring close monitoring and prompt treatment.

COVID-19 and related complications:

• 6% with tafa experienced COVID-19 infections compared to 2% with placebo.
• COVID-19 pneumonia was reported in 5% with tafa versus 1% with placebo.
• The study was performed at the height of the COVID-19 pandemic.

Why This Matters for You

This study is the first to show that combining two antibodies targeting different lymphoma markers—CD19 and CD20—can improve outcomes for people with FL. For follicular lymphoma patients and caregivers, this means:

1. Longer periods without disease progression: Tafa significantly extended the time before the disease returned or worsened.
2. Improved tumor response: More patients achieved complete or partial remission with the combination therapy.
3. Manageable side effects: The safety profile of tafa + len + R was consistent with what’s expected for these types of treatments.

What This Means for the Future

The results suggest that tafasitamab + len + R could become a new standard of care for patients with relapsed or refractory FL. This combination can be administered in both community and academic treatment centers, making it accessible to a wide range of patients. Although overall survival (OS) data are still maturing, early trends show promise.

Questions to Discuss with Your Doctor

If you or your loved one is dealing with relapsed/refractory follicular lymphoma, consider asking:

• Could this combination therapy be right for me?
• What are the potential risks and benefits of this treatment?
• Are there ongoing clinical trials exploring similar approaches?

Conclusion

The inMIND study offers new hope for follicular lymphoma patients by validating the use of a novel combination therapy. As more research emerges, this approach may provide a durable, effective option for managing this challenging disease.

For more important ASH Coverage on emerging follicular lymphoma research, stay tuned to our HealthTree website in the coming month: HealthTree Conference Coverage