Safety and Activity of Intensive Short-Term Chemoimmunotherapy in HIV-Positive (HIV+) Patients (pts) with Burkitt Lymphoma (BL)

Worldwide experience with intensive chemotherapy plus HAART in HIV+ pts with BL is still limited. In a few available studies, this strategy was associated with complete remission (CR) rates of 70–80% and 2-year overall survival (OS) rates of 45–70%, but with a treatment-related mortality of 15–20%, mostly due to septic complications. We adapted an intensive short-term chemotherapy program used for HIV-negative childhood and adult pts with BL [Di Nicola M, et al. BJH 2004] to treat HIV+ pts with maintained efficacy and lower toxicity. Herein, we report feasibility and activity of this program addressed in a multicenter pilot experience.

Consecutive HIV+ pts with BL, age ≤65 yrs and ECOG-PS ≤3 were treated with an intensified program at three Institutions. The program included a 38-day Induction Phase (IP) of sequential doses of methylprednisolone, cyclophosphamide, vincristine, rituximab, methotrexate, VP-16, and doxorubicin, with intrathecal prophylaxis/treatment. After IP, pts in CR received consolidation phase (CP; cytarabine+cisplatin+rituximab); pts in PR received CP followed by BEAM + ASCT; pts with SD or PD received intensification phase (R-ICEx2 + high-dose cyclophosphamide + high-dose cytarabine + BEAM + ASCT). Leukaphereses were performed after CP. Pts with residual or bulky disease received consolidation radiotherapy.

13 pts (median age 42 yrs, range 27–63; all males; ECOG-PS >1 in 5) were considered. Most pts had advanced stage, increased LDH, B symptoms, bulky lesions, and extranodal disease (meningeal in 2). Eight pts received HAART before BL; median CD4+ cells at BL diagnosis was 272 (range 17–858; 4 pts had CD4+ <200 c/μL).

Twelve pts completed IP (median duration 48 days; range 38–54), with some delay in 8 pts (median 3 days, range 1–14); 1 pt died of sepsis (CD4+= 17 c/μL). Dose reductions were not recorded. During the IP, G3-G4 haematological toxicity was observed in all pts: neutropenia in 12, thrombocytopenia in 5 and anaemia in 7. RBC and platelets transfusions were indicated in four and five patients, respectively. With conventional antimicrobial prophylaxis and G-CSF support, 12 pts had infections, with CMV reactivation in 5. Only 1 pt had G4 non-hematological toxicity (transient diarrhea).

Response after IP was CR in 6 pts and PR in 5, with an ORR of 85% (95%CI: 66–100%); 1 pt experienced meningeal PD. Per protocol (Fig. 1), the 6 CRs received CP and were referred to follow-up; the 5 PRs received CP followed by BEAM + RT in three pts and by intensification in two pts who experienced PD after CP; the pt who experienced PD after IP was referred to intensification.

Overall, 11 pts were referred to CP; the first 4 experienced prolonged G4 neutropenia and infections, including CMV and EBV reactivations; thus, the following 7 pts were treated only with cytarabine-rituximab as CP; none of them experience infectious events. Leukaphereses were successful in 7 of the 9 referred pts. Response after the whole program was CR in 9 pts (CRR= 69%; 95%CI: 44–94%); intensification is ongoing in 2 failed pts and 1 pt died of lymphoma. At a median follow-up of 16 months (range 4–24), none of the 9 pts who achieved CR and completed the whole program experienced relapse; 11 pts are alive (9 in CR), one pt died of BL and one of sepsis, with a 2-year OS of 81%.

This pilot experience suggests that this intensive short-term program is feasible in HIV+ pts with BL. The proposed program shows a better tolerability profile and a similar activity respect to other more demanding and resource consuming regimens. A multicenter prospective phase II trial is warranted.

Off Label Use: ofatumumab, in label for CLL.