Evolving Treatment Landscape Presents Patients With Indolent Non-Hodgkin Lymphoma 'Lots of Options'

The landscape for treating patients with indolent non-Hodgkin lymphoma continues to evolve, making it a challenge to optimize frontline and recurrent treatment, however, there are promising agents on the horizon, according to Dr. Brad S. Kahl.

In the frontline setting alone, Dr. Khal, of the Siteman Cancer Center in St. Louis, explained that the first question that needs to be answered is whether a patient with indolent non-Hodgkin lymphoma (iNHL) needs to receive treatment immediately. This is because some patients are asymptomatic and have a low tumor burden, so they will not require treatment until symptoms develop or have a high tumor burden, explained Kahl.

Moreover, treatments used for iNHL vary between the lymphoma types, but typically in the frontline setting physicians use Bendeka (bendamustine) in combination with Rituxan (rituximab). This treatment is mostly well tolerated in patients; however, older patients can struggle with this combination and are then given single-agent Rituxan. Then, younger patients with a more aggressive form of iNHL would be better suited for a more in-depth combination treatment of Rituxan, cyclophosphamide (chemotherapy), doxorubicin (chemotherapy), vincristine (chemotherapy) and prednisone (R-CHOP).

“The management of [recurrent] indolent lymphoma is complicated because there are so many variables,” said Khal, in an interview with OncLive^®, a sister publication to CURE^®. "There are lot of treatment options and factors to consider, including a patient's age and fitness, their prior lines of therapy, and how well those previous therapies worked for them. It is hard to have a blueprint of how to manage these patients."

Managing patients with recurrent iNHL is also a matter of assessing the individual patient after their treatment as plans will vary based on a number of factors. For instance, maintenance therapy can weaken a patient’s immune system, explained Kahl, which can lead to hypogammaglobulinemia (a problem where not enough gamma globulins are produced in the blood which results in a low antibody count) that then leads to recurrent infections.

“Some physicians routinely administer maintenance therapy, others never do, and some make it optional. I tend to make it optional,” Kahl said. “I'll prescribe maintenance therapy to a patient, explain what it can do for them, and then [let the patient decide]. Maintenance therapy can extend a patient’s first remission, but it does not appear to impact overall survival (OS). If it did improve OS, all patients would receive maintenance therapy.”

One of the main challenges that Kahl cited for treating patients with iNHL, especially for recurrent indolent lymphoma, is trying to find agents with a longer durable response. Currently, the main treatment for these patients with recurrent indolent lymphoma is PI3K inhibitors and Imbruvica (ibrutinib), drugs that target proteins related to cancer cell development, but the median progression free survival for patients on this therapy typically a year, according to Khal. Meaning patients will need another option after the first year.

New options are on the horizon, however, as researchers look at new antibody therapies and the use of CAR-T cell therapies. Kahl, also discussed the promise of immunotherapy agents that demonstrated responses in the 50-60% range, but cautioned patience as durability still needed to be assessed.

“We have a lot of options, which is a good problem to have. It does make the decision-making process more complicated, but I am grateful to have these options to manage patients with recurrent indolent lymphoma,” he said. “One needs to take a thoughtful long-term strategy when making these decisions for their patients.”