This international multicentre open-label phase II trial investigated whether the subsequent use of rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy would improve the outcome of CD20-positive post-transplantation lymphoproliferative disorder (PTLD) who had failed upfront immunosuppression reduction.
74 treatment-naive adult solid-organ transplant recipients were enrolled. 70 of these patients received four courses of rituximab (375 mg/m2) once a week followed by four weeks without treatment and four cycles of CHOP every three weeks. In case of disease progression during rituximab monotherapy, CHOP was started immediately. Supportive therapy with granulocyte-colony stimulating factor after chemotherapy was mandatory and antibiotic prophylaxis was recommended.
The primary endpoint was response rate in all patients who completed treatment with rituximab and CHOP, per protocol, and response duration, in all patients who completed all planned therapy and responded.
The following findings were reported:
- PTLD was of late type in 53 (76%) of 70 patients, monomorphic in 67 (96%) of 70, and histologically EBV associated in 29 (44%) of 66 cases.
- 4 of 70 patients did not receive CHOP.
- 53 of 59 patients had a complete or partial response (90%, 95% CI 79—96), of which 40 (68%, 55—78) were complete responses.
- At data cut-off (June 1, 2011) median response duration in the 53 patients who had responded to treatment had not yet been reached (>79.1 months).
- The main adverse events were grade 3—4 leucopoenia in 42 of 62 patients (68%, 55—78) and infections of grade 3—4 in 26 of 64 patients (41%, 29—53).
- 7 of 66 patients (11%, 5—21) had CHOP-associated treatment-related mortality.
- Median overall survival was 6•6 years (95% CI 2.8—10.4; n=70).
The researchers concluded that their results support the use of sequential immunochemotherapy with rituximab and CHOP in PTLD.