Two Immunotherapies May Address Unmet Need in Mantle Cell Lymphoma

While the treatment landscape of mantle cell lymphoma (MCL) has continued to evolve in recent years, researchers and clinicians alike are still at a loss for curative strategies, according to Brad Kahl, M.D.

However, there are some clinical trials that are seeking to change that, Kahl, a professor in the department of Medicine at Washington University School of Medicine in St. Lous, Siteman Cancer Center, told OncLive, a sister publication of CURE.

“The biggest unmet need for MCL is that we don’t cure it. We need curative strategies for MCL so we do not have this relentless disease with this continuation of relapse and needing subsequent salvage therapy,” he said.

The SHINE trial

SHINE is a phase 3 trial investigating Imbruvica (ibrutinib) in combination with bendamustine and Rituxan (rituximab) in patients over the age of 65 who are newly diagnosed with MCL and not eligible for stem cell transplant.

The primary endpoint of the trial is progression-free survival (PFS), with overall survival, overall response rates (ORR) and duration of response (DoR) all being secondary endpoints. Patients on the experimental arm will receive Imbruvica each day until disease progression or until side effects become unacceptable. They will also get intravenous (IV) bendamustine on days one and two of cycles one through six, and IV Rituxan on the first day of the first and sixth cycle.

“The SHINE trial is fully enrolled, but we do not have any readout yet from that trial. If it is a strongly positive trial, it has the potential to change the standard of care in frontline MCL — at least for older patients,” Kahl said.

The ZUMA-2 Trial

Another study — the multicenter phase 2 ZUMA-2 trial – is testing the use of the chimeric antigen receptor (CAR)-T cell therapy Yescarta (axicabtagene ciloleucel; axi-cel) in patients with relapsed or refractory MCL.

Positive results from this trial would be particularly exciting, as they may lead to new treatment options for patients who are resistant to BTK inhibitors such as Imbruvica. The primary endpoint of the trial is ORR. Secondary endpoints are DoR, best objective response rates and PFS. The trial is still enrolling patients.

“CAR T cells have a lot of potential in MCL. As I mentioned, MCL is not curable right now, so eventually, all patients relapse and need second-, third- and fourth-line settings,” Kahl said. “Ibrutinib and acalabrutinib (Calquence) are very effective, but their benefit is finite. They do not work forever.”

Kahl mentioned that there is not enough data on CAR-T cell therapy in this field, but in another year or two, researchers will know a lot more, and hopefully be closer to a cure — or at least improved outcomes.