To The Editor: Ofatumumab (Ofa) is a new monoclonal anti-CD20 antibody with a high efficacy in fludarabine- and alemtuzumab-refractory B cell chronic lymphocytic leukemia (B-CLL) [1, 2]. Data showing an advantage with the addiction of high dose corticosteroids to the Ofa at standard dose in this type of patients, obtaining an OR rate of 78%, have recently been published in the literature .
Here, we describe our experience with intravenous high-dose corticosteroids in combination with “low-dose” Ofa as a salvage regimen for fludarabine/alemtuzumab-refractory B-CLL patients. The following administration schedule was used: a test dose (300 mg) of Ofa was given on Day 1, followed by 6 doses of 2,000 mg starting from Day 7 every 28 days, in combination with high-dose methylprednisolone (HDMP, 1 g/m2/day) which was given intravenously for 5 days every 28 days, for six consecutive cycles or until disease progression. All patients received a pre-medication with diphenhydramine and paracetamol before each Ofa infusion, and a prophylaxis with co-trimoxazole and acyclovir. Since our patients were at high risk of infection due to the underlying disease, to the several previous therapeutic regimens (including in one case allogeneic stem cell transplantation), and to the presence of Grade 3 neutropenia, we used “low-dose” Ofa to reduce the risk of infectious complications [4, 5]. Three Rai Stage IV, Binet Stage C patients underwent therapy . The median number of previous lines of therapy was 4. The median time from the last therapy was 1 month (range, 1–3 months). All patients had Grade 3 neutropenia, with one patient being transfusion dependent because of anemia and thrombocytopenia (toxicity levels were graded according to the NCI CTCAE v 4.0 scale) [http://ctep. cancer.gov/reporting/ctc.html]. All patients showed a massive bone marrow involvement at the beginning of the treatment. Unfavourable cytogenetic was present in 2 of 3 patients (patients' characteristics are reported in TableI).
|Patients||No. 1||No. 2||No. 3|
|Disease duration (years)||5||9||12|
|Lymphocyte counta||40.15 × 109/L||10.32 × 109/L||3.78 × 109/L|
|Bone marrow lymphocytesa||93%||90%||80%|
|Neutrophil counta||0.70 × 109/L||0.59 × 109/L||0.78 × 109/L|
|Bulky disease(node >5 cm by CT scan)||no||massive splenomegaly||massive splenomegaly|
|Prior treatment||FluCam, FCC Benda-R||FC, FCR, L-PDN, Benda-R, CHL-PDN, Cam||Flu, FC, FCR-L, Allo-SCT|
|Response to the last treatment||PD||PD||PD|
Assessment of response was performed according to NCI-WG criteria . We obtained an overall response rate (ORR) of 66% (two partial response). One patient (Patient no. 3) died from progressive disease after the third Ofa-HDMP cycle. The therapy itself was well tolerated. No patients required support with growth factors or hospitalization. We did observe a worsening of neutropenia until the 4th Ofa-HDMP cycle (Patients no. 2 and 3); subsequently, however, responding patients showed a rise in neutrophil count followed by normalization. Patient no. 2 became free from transfusion dependency with the 3rd Ofa-HDMP cycle. Mild extra-hematological side effects including fatigue, fluid retention, hyperglycemia, and hypokalemia were observed . No infusion related reactions were observed. None of the patients developed fever or evidence of bacterial, viral, or fungal infection during the planned treatment.
We confirm that the addition of HDMP to Ofa is an effective and safe salvage therapy for pre-treated B-CLL patients. Moreover, delaying Ofa administration on a monthly basis allowed us to complete the treatment plan with mild toxicity in a setting of patients heavily pre-treated and presenting with severe pancytopenia.