What's In Store for Hematologic Malignancies?

Andrew D. Zelenetz, M.D., Ph.D. weighs in on recent research and the future of treating hematologic malignancies.
Research is needed in the first-line treatment of hematologic malignancies, according to Andrew D. Zelenetz, M.D., Ph.D.

For patients with indolent lymphoma or chronic lymphocytic leukemia (CLL), the optimal frontline choice does not exactly exist, he says. While treatment options have evolved and improved over time, researchers are still debating between bendamustine- or CHOP-based regimens for follicular lymphoma, for example. And while chemoimmunotherapy remains a standard frontline approach for younger, fit patients with CLL, it’s not as clear as to what is best for the older patient population.

Zelenetz, the medical director of Quality Informatics at Memorial Sloan Kettering Cancer Center, spoke on indolent lymphoma and CLL treatment in an interview with CURE.

Can you provide an overview of the current landscape of indolent lymphoma?

When you are diagnosed with follicular lymphoma, your expected survival is inferior to the age match general population, but not by very much. The median survivals in this disease have changed from eight to 10 years 25 years ago, to 16 to 20 years as a median survival today.

We know that first-line therapy is important. First-line therapy can result in long progression-free survival (PFS). We’re still struggling to find the optimal first-line therapy, whether it’s bendamustine-based, or CHOP or CVP; the answer is not crystal clear.

One of the interesting things we saw from the 2016 ASH Annual Meeting is what’s called the GALLIUM trial, which is bendamustine plus CHOP or CVP combined with Rituxan (rituximab) or Gazyva (obinutuzumab). This was a head-to-head comparison of Rituxan versus Gazyva in indolent lymphoma. The follicular lymphoma cohort was spoken about at the presentation, while the non-follicular indolent cohort wasn’t. It actually met its endpoint. The statistical plan was looking for an improvement (with Gazyva)—a hazard ratio of 0.74. The hazard ratio is 0.66. That corresponds to a 50 percent increase in the PFS.

People think that not much has been accomplished because the curves don’t look that different, but the curves can’t look that different. A 50 percent increase in PFS is going to correlate to about a 10-year survival after first-line therapy. That’s pretty impressive, and it’s going to be hard to beat. We have a large, randomized study comparing Rituxan and Revlimid (lenalidomide) with Rituxan chemotherapy, but it’s going to be hard to beat a median PFS of 10 years with chemoimmunotherapy.

What about the CLL landscape?

In the CLL world, we are still struggling with first-line therapy. There’s a group of patients, particularly young, fit patients with mutated immunoglobulin genes, who have a 10-year PFS in the range of 70 percent. They’re probably cured. There are very few events in that group of patients. From that group, which is a very small group, we can define a standard of care, which is FCR (fludarabine, cyclophosphamide, and Rituxan).

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