Introduction: CD22 is expressed on most B-non-Hodgkin lymphomas (NHL);
inotuzumab ozogamicin (INO) is an anti-CD22 antibody conjugated to calicheamicin.
This study evaluated the safety and tolerability of INO plus R-CVP in patients (pts) with
relapsed/refractory CD22+ B-NHL. Efficacy data were also collected.
Methods: Part 1 of this open-label study identified a maximum tolerated dose (MTD)
of INO 0.8mg/m,2 on day 2 plus R-CVP (rituximab 375mg/m,2 cyclophosphamide
750mg/m,2 and vincristine 1.4mg/m,2 on day 1; prednisone 40mg/m,2 on days 1-5)
every 21 days. Subsequently, pts were enrolled in the MTD confirmation cohort (part
2, n = 10), which required a dose-limiting toxicity rate of <33% in cycle 1 and <4
pts discontinuing prior to cycle 3 due to an adverse event (AE) in the MTD expansion
cohort (part 3, n = 22), which explored preliminary activity.
Results: Parts 2 and 3 enrolled 32 pts: 16 pts with diffuse large B-cell lymphoma, 15
with follicular lymphoma and one with mantle cell lymphoma. Median age was
64.5 years (range 44-81 years); 34% of pts had 1 prior regimen, 34% had 2, 28% had
≥3 and 3% had none (median 2; range 0-6).Median treatment duration was five cycles
(range 1-6). Part 2 confirmed the MTD as standard dose R-CVP plus INO 0.8mg/m,2;
2/10 pts had a dose-limiting toxicity (grade 3 increased ALT/AST, grade 4 neutropenia
requiring G-CSF). One pt discontinued because of an AE prior to cycle 3.
Common treatment-related AEs were thrombocytopenia (78%), neutropenia (66%), fatigue
(50%), leukopenia (50%), nausea (41%) and lymphopenia (38%); common grade
3/4 AEs were neutropenia (63%), thrombocytopenia (53%), leukopenia (38%) and
lymphopenia (31%). There was one case of treatment-related fatal pneumonia with
grade 4 neutropenia. Ten pts discontinued treatment due to AEs; thrombocytopenia/delayed
platelet recovery was the leading cause (grade 1/2, n = 6; grade 3/4, n = 3). Objective
response rate (ORR) was 77% (n = 24/31 evaluable pts), including 26% (n=8/31)
with complete response (CR); three pts had stable disease. Of the pts with follicular
lymphoma, ORR was 100% (n = 15/15), including seven pts with CR. Of the pts with
diffuse large B-cell lymphoma, ORR was 60% (n = 9/16), including one pt with CR.
Conclusions: Results suggest that INOplus R-CVP has acceptable toxicity and promising
activity in relapsed/refractory CD22+ B-NHL. The most common grade 3/4 AEs were
hematologic. Follow-up for progression-free and overall survival is ongoing.