Triplet disappoints in follicular lymphoma trial
Photo courtesy of ASH
ORLANDO, FL—A 3-drug regimen is likely not worth pursuing as a first-line treatment option for follicular lymphoma (FL), according to a presentation at the 2015 ASH Annual Meeting.
In a phase 1 study, combination ibrutinib, rituximab, and lenalidomide did not provide any response benefit over that previously observed with rituximab and lenalidomide.
But the triplet increased toxicity—particularly the incidence of rash—and necessitated dose modifications.
Chaitra S. Ujjani, MD, of Georgetown University Hospital in Washington, DC, presented these results at the meeting as abstract 471.*
“The combination of rituximab and lenalidomide has demonstrated remarkable activity in follicular lymphoma,” Dr Ujjani began.
She noted that, in the CALGB 50401 trial of relapsed FL (Leonard et al. JCO 2015), the combination elicited an overall response rate (ORR) of 76% and a complete response (CR) rate of 39%, and the 2-year time to progression was 52%.
In the CALGB 50803 trial of previously untreated FL (Martin et al. ASCO 2014, 8521), the regimen produced an ORR of 96%, a CR rate of 71%, and a 2-year progression-free survival (PFS) of 89%. In another trial of previously untreated FL (Fowler et al. Lanc Onc 2014), the ORR was 90%, the CR rate was 80%, and the 3-year PFS was 79%.
Ibrutinib has also demonstrated activity in FL, Dr Ujjani pointed out. In a phase 1 study of relapsed FL (Fowler et al. ASH 2012), the drug produced an ORR of 55%, 3 of 11 patients achieved a CR, and the median PFS was 13.4 months.
In a phase 2 study of ibrutinib in relapsed FL (Bartlett et al. ASH 2014, 800), the ORR was 30%, 1 of 40 patients achieved a CR, and the median PFS was 9.9 months.
With this in mind, Dr Ujjani and her colleagues conducted the A051103 trial to determine the activity and tolerability of rituximab, lenalidomide, and ibrutinib in previously untreated patients with FL.
Study design
The study enrolled patients with grade 1-3a FL; stage III, IV, or bulky stage II disease; an ECOG performance status less than 2; and adequate organ function.
They received 4 doses of rituximab at 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 (28 days). They received 4 additional doses (375 mg/m2) on day 1 of cycles 4, 6, 8, and 10.
The patients received lenalidomide according to their assigned dosing cohort on days 1 to 21 for 18 cycles. They received daily ibrutinib according to their assigned dosing cohort until progression or unacceptable toxicity.
The study had a 3+3 dose-escalation design. Dose level (DL) 0 was lenalidomide at 15 mg and ibrutinib at 420 mg, DL1 was lenalidomide at 15 mg and ibrutinib at 560 mg, and DL2 was lenalidomide at 20 mg and ibrutinib at 560 mg.
Patients also received allopurinol at 300 mg daily for tumor lysis prophylaxis and aspirin as thromboprophylaxis while on lenalidomide.
The researchers assessed dose-limiting toxicities (DLTs) weekly during cycle 1. Given the known incidence of rash with lenalidomide, grade 3 rash that resolved to less than grade 2 within 10 days was not included as a DLT.
Once the maximum-tolerated dose was determined, there was a 10-patient expansion cohort.
Patients and treatment
Twenty-two patients were enrolled between June 2013 and May 2015. Their median age was 53.5 years (range, 36-81), and 68% were male.
Seventy-three percent of patients had grade 1/2 disease, and 77% had stage IV disease. By FLIPI, 18% of patients were low-risk, 55% were intermediate-risk, and 27% were high-risk.
