Ofatumumab ( Arzerra ) is a fully human monoclonal antibody that binds to both the large and small extracellular loops of CD20. Ofatumumab is currently approved for patients with refractory chronic lymphocytic leukemia and has demonstrated activity in non-Hodgkins lymphomas, including follicular lymphoma ( FL ).
Researchers previously reported results of a phase II study of Ofatumumab in combination with CHOP ( Cyclophosphamide 750 mg/m2, Doxorubicin 50 mg/m2, Vincristine 1.4 mg/m2, Prednisone 100 mg daily for 5 days ) chemotherapy ( O-CHOP ) in patients with previously untreated follicular lymphoma ( Czuczman et al. Br J Haematol. 2012;157:438 ).
Researchers have now reported updated efficacy, safety and pharmacokinetic ( PK ) follow-up data for this study.
Fifty-nine patients with previously untreated follicular lymphoma were randomized to Ofatumumab 500 mg ( n=29 ) or 1000 mg ( n=30 ) on day 1, with CHOP on day 3, every 3 weeks for 6 cycles.
The primary end point was overall response rate ( ORR ), as assessed by an independent end points review committee.
Secondary end points included complete response ( CR ), progression-free survival ( PFS ), overall survival, adverse events ( AEs ) and PK.
Follow-up assessments after therapy were done every 3 months until month 12 and then every 6 months until alternative follicular lymphoma therapy or month 60.
Positron emission tomography ( PET ) was done at baseline and 3 month after last therapy. Blood samples for PK analyses were collected to determine Ofatumumab serum concentrations, and noncompartmental methods were used to estimate PK parameter values.
Fifty-eight patients received therapy; 1 patient in the 1000-mg group withdrew before initiation of therapy.
The ORR was 90% for the 500-mg group ( n=29 ) and 100% for the 1000-mg group ( n=29 ); 55% of patients achieved CR or unconfirmed CR ( Cru ), including 67% of patients with a Follicular Lymphoma International Prognostic Index ( FLIPI ) score of 3-5.
At baseline, 57 patients were PET positive, and 49 patients underwent repeat PET scans after therapy. Forty of 49 patients ( 82% ) became PET negative, including 27 of 29 ( 93% ) patients who achieved CR/CRu and 13 of 20 patients ( 65% ) who achieved partial response ( PR ).
With a median follow-up of 33.8 months, the median PFS for the 500-mg group was 27.6 months and the median PFS for the 1000-mg group was not reached ( P=0.46 ).
Median PFS for patients with FLIPI scores of 0-1 ( n=17 ), 2 ( n=20 ) and 3-5 ( n=21 ) was not reached, 27.6 months and 27.6 months, respectively ( P=0.68 ).
Median PFS for patients ( n=32 ) who achieved CR/CRu was also not reached and was 28.3 months for patients ( n=23 ) achieving PR.
Median PFS for PR patients who were PET positive and PET negative after therapy was not reached and 28.3 months, respectively.
No deaths have been reported. No hematologic serious adverse effects ( SAEs ) were experienced during the follow-up period. During the follow-up period, non-hematologic SAEs were reported in 1 patient in the 500-mg group ( pneumonia ) and 5 patients in the 1000-mg group ( abdominal hernia, erysipelas, intervertebral disc protrusion, meniscus lesion and vulval cancer ); none were Ofatumumab-related.
After repeated dosing, Ofatumumab clearance values were 6.3 and 5.9 mL/h, and half-life values were 27.2 and 26.8 days in the 500-mg and 1000-mg groups, respectively.
In conclusion, O-CHOP achieved durable remissions in previously untreated patients with follicular lymphoma. There were no observed PK or PFS differences between the 500-mg and 1000-mg arms, but the study was not powered to detect such differences.
O-CHOP was effective in patients with high-risk FLIPI scores, and CR/CRu and PFS rates were not affected by FLIPI score.
PET status after therapy did not predict PFS in responding patients, although the study was too small to make such a determination. These results indicate that O-CHOP should be studied as a therapy for follicular lymphoma with high-risk FLIPI scores.
Source: 54th ASH Annual Meeting, 2012