Bortezomib Boosts Complete Remissions in High-Risk Follicular Lymphoma

Adding bortezomib to bendamustine/rituximab (BR) significantly improves complete remission (CR) rates in previously untreated high-risk follicular lymphoma, according to a new study (abstract 7507) presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago.

Despite good progress in the treatment of high tumor burden follicular lymphoma, “this disease remains remitting and relapsing for most patients, and the vast majority are not cured,” said Andrew M. Evens, DO, MSc, of Tufts Medical Center in Boston.

Evens reported on a randomized, phase II trial with the goal of improving outcomes of standard treatment strategies by incorporating new or novel therapeutic agents in untreated high-risk follicular lymphoma.

The 236 evaluable patients had untreated high-risk grade I/II or IIIa follicular lymphoma. Patients were randomized to BR for 6 cycles followed by maintenance rituximab for 2 years; BR plus bortezomib for 6 cycles then maintenance rituximab for 2 years; or BR for 6 cycles then maintenance rituximab for 2 years plus lenalidomide for 1 year.

This analysis used CR as the primary objective since achieving CR may be a potentially important surrogate of survival, Evens said.

The CR analyses were based on 222 patients, including 85 patients who received BR plus bortezomib and 137 patients who received BR. The two arms were well balanced, with a median age of about 60. Most patients had ECOG Performance Status of 0 or 1; one quarter had extranodal sites and about two-thirds had marrow involvement. Some 86% of all patients received the 6 planned induction cycles.

The overall response rate was 91% for the BR plus bortezomib and BR groups. CR rates were significantly higher for BR plus bortezomib (74%) than BR (58%).

There were two deaths during induction, one due to an opioid overdose and the other due to progressive disease. Less than 10% of all patients went off treatment due to progressive disease and toxicity.

In general, the therapies were well tolerated, he said. The most common grade 3/4 toxicities were similar for BR plus bortezomib versus BR, including neutropenia, thrombocytopenia, fatigue, febrile neutropenia, and diarrhea. Grade 3 sensory neuropathy was significantly higher in the BR plus bortezomib group (12%) as compared to the BR group (1%). Evens noted that this occurred mostly in patients who received intravenous bortezomib, and was “less dramatic” for patients who received subcutaneous bortezomib.

“The addition of bortezomib to BR as frontline induction appears to be feasible in high tumor burden [follicular lymphoma],” said Evens. “This initial report shows that the CR rate for BR plus bortezomib was significantly improved than with BR. The big question is does CR correlate with survival? We await survival data to analyze for potential association with CR.”

Continued follow-up is also needed to assess whether lenalidomide adds to maintenance rituximab to improve outcomes.

Detailed correlative studies are planned. “We have collected tissue blocks, bone marrow, and PET scans for most patients, and have more than 3,000 peripheral blood samples,” Evens said. “We will look at host [single nucleotide polymorphisms], minimal residual disease, and potential sequencing of tissues.”