Efficacy of Bortezomib Plus CHOP Combination Therapy on Angioimmunoblastic T Cell Lymphoma: Clinical Results in Three Patients

Objectives:To investigate the efficacy and safety profile of bortezomib (VELCADE) plus CHOP combination therapy (V-CHOP) on angioimmunoblastic T cell lymphoma (AITL).

Patient information and Methods:All three patients were male with a mean age of 51.3 y/o (40–63). One patient was chemo-naïve and the other two suffered from refractory or relapsed disease. The clinical manifestation included progressive superficial lymphadenectasis (bilateral lymph nodes of the neck, supraclavicular, axillary, inguinal) and lymphadenectasis of the deep lymph nodes (mediastinal and celiac lymph nodes). The largest lymph node diameter under B ultra-sound for the three patients were 1.1cm*1.1cm A1.8cm*1.5cm and 1.6cm*1.7cm respectively. The patients also had fever, splenohepatomegalia and serous cavity effusion. As for the two refractory/relapsed patients, their former chemotherapy included CHOP, ICE, E-CHOP, FLAG. But their diseases continued to progress despite of three times and twelve times of chemotherapy as well as local radiotherapy respectively. The chemotherapy used to treat these patients was V-CHOP (Bortezomib 1.6mg/m2 on Day1and 8; cytoxan 75mg/m2 on Day 1, adriamycin 60mg/m2 on Day 1, vincristine 1.4mg/m2 on Day 1, prednisone 100mg on Day 1, 2, 3, 4 and Day 5) ( 21 days for each cycle). The efficacy of the therapy was determined by Revised Response Criteria for Malignant Lymphoma(2007 by American Society of Clinical Oncology) Gthe adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0 (NCI CTCAE V3.0)and the dosage adjustments were made in compliance with the grading.

Results:(Efficacy) After two cycles of V-CHOP, the chemo-naïve patient withdrew from the study for disease progression while the two refractory/relapsed patients returned to normal body temperature with the disappearance of serous cavity effusion and splenohepatomegalia. These two patients also had >50% decrease of the largest lymph node diameter and achieved partial response (PR). After a further 4 cycles of maintenance V-CHOP therapy, the two patients maintained PR with the duration of response of 6 months and 9 months respectively (by Aug, 2008, still going on). (Adverse Events)Hematological toxicity: leucocytopenia and thrombocytopenia of Grade 3–4 in all 3 subjects (100%), recovering after G-CSF and platelets infusion.Non-hematological toxicity: weakness of Grade 1–2 (100%), neuropathy of Grade 1 (33%), recovered spontaneously without treatment; herpes zoster reactivation(33%, after 4 cycles of V-CHOP), recovered after anti-virus therapy and supportive treatment.

Conclusion:V-CHOP was utilized to treat three patients with refractory/relapsed AITL. One patient withdrew for lack of response while the other two patients achieved PR after the initial 2 cycles of treatment with the duration of response of more than 6 months. These results suggest the V-CHOP, at least for some refractory/relapsed AITL patients, can induce quality and rapid response which can last for a relatively long time. The adverse events are often mild to moderate and resolved spontaneously or after supportive treatment.