A phase 3, randomized study of ofatumumab combined with bendamustine in rituximab‐refractory iNHL (COMPLEMENT A + B study)

Abstract

Summary The standard of care for indolent non‐Hodgkin lymphoma (iNHL) is rituximab, an anti‐CD20 antibody, with/without chemotherapy. However, multiple relapses are common in these patients. This phase 3, randomized study compared outcomes of a combination of ofatumumab (a second‐generation anti‐CD20 antibody) and bendamustine, with bendamustine alone in patients unresponsive to prior rituximab‐based treatment. Overall, 346 patients were randomized to receive either the combination or bendamustine alone. Bendamustine was given for ≤8 cycles and ofatumumab for ≤12 cycles. The primary end‐point was progression‐free survival (PFS) after 215 protocol‐defined events assessed by independent review committee (IRC). Median IRC‐assessed PFS was 16·7 and 13·8 months in the combination and monotherapy arms respectively [hazard ratio (HR) = 0·82; P = 0·1390]. Median overall survival (OS) was 58·2 and 51·8 months in the combination and monotherapy arms respectively (HR = 0·89, P = 0·4968). The safety profile was consistent with previous reports. Overall, 73% and 80% of patients in the combination and monotherapy arms, respectively, experienced a ≥grade 3 adverse event. The study did not meet its primary end‐point. No significant improvement in PFS and OS was seen with the combination of ofatumumab and bendamustine as compared with bendamustine alone in rituximab‐refractory iNHL (NCT01077518).

Novel Immune-Based treatments for Diffuse Large B-Cell Lymphoma: The Post-CAR T Cell Era

“…Obinutuzumab is a mAb with a modified Fc portion which provides a more potent ADCC activity than rituximab and less potent complement-dependent cytotoxicity ( 38 ). In a randomized phase 3 study of obinutuzumab-CHOP versus rituximab-CHOP, obinutuzumab did not show superior outcomes in DLBCL patients compared to rituximab but resulted in more adverse events including infections, fever, and cytopenias ( 39 – 41 ). Radiolabeled CD20 mAbs such as ibritumomab tiuxetan (Zevalin) and I-131 tositumomab (Bexxar) are also used in treatment of DLBCL ( 42 , 43 ).…”

Role of antibody-based therapy in indolent non-Hodgkin's lymphoma

“…The study was closed early for futility as superiority was seen in the rituximab arm with an ORR of 66% compared to 50% in the ofatumumab arm ( P = 0.0011) [15] . Similarly, the combination of bendamustine with ofatumumab showed no end of induction clinical benefit compared with single agent bendamutine in rituximab-refractory iNHL, but improvement in PFS with median of 16.7 vs 13.8 months due to the maintenance arm [16] .…”

“…Based on the BRIGHT and the STIL trials, Rituximab (R) in combination with bendamustine became a wildly adopted regimen in frontline iNHL given its relatively favorable toxicity profile compared to R-CHOP [ 7 , 8 ][ 16 ]. However, due to the adverse effects of cytotoxic chemotherapy, there has been increased interest in a chemo-free approaches for frontline and R/R FL ( Table 1 ).…”

Current and emerging monoclonal antibodies, antibody-drug conjugates, and bispecific antibodies in treatment of lymphoma

“…However, ofatumumab failed to show improvement in outcomes (ORR, CR, OS and PFS) over rituximab with more adverse events in those who received ofatumumab [20] . In a phase 3 trial (NCT01077518), the addition of ofatumumab to bendamustine in NHL patients refractory to rituximab, failed to improve OS and PFS [21] .…”