Rituximab + ESHAP as Salvage Chemotherapy for Relapsed/Refractory Aggressive Non-Hodgkins Lymphoma: A Phase II Trial.

Background: Patients with relapsed or refractory aggressive B-cell lymphoma have a poor prognosis. If sensitive to salvage chemotherapy, high dose therapy followed by autologous stem cell transplant (ASCT) can result in long-term survival for some. Unfortunately, 50% of patients are insensitive to standard salvage regimens and thus are ineligible for ASCT.

Hypothesis: Combining Rituximab with ESHAP may improve chemosensitivity and ASCT eligibility, of patients with CD20+, relapsed or refractory aggressive lymphoma, or CD20+ transformed indolent lymphoma.

Objectives: The primary outcome was response rate (CR + CRu + PR) to R-ESHAP. Secondary outcomes were toxicity, ability to undergo ASCT, presence of minimal resdidual disease in the stem cell harvest, and progression free and overall survival.

Methods: Eligible patients were 16–65 years old, had ECOG performance status 0–2, and had pathologically confirmed CD20+, relapsed/refractory aggressive lymphoma or transformed indolent lymphoma. Patients with refractory disease had a PR with initial anthracycline-based therapy. ESHAP (etoposide 40mg/m² day 1–4, solumderol 500mg day 1–5, cytosine arabinoside 2g/m² day 5, cisplatin 25mg/m² day 1–4) was given every 28 days with GCSF support until < 15% bone marrow involvement was achieved (2–4 cycles). Eight infusions of Rituximab (375mg/m²) were administered weekly concurrent with the first 2 cycles of ESHAP. GCSF mobilized stems cells were collected on day 10 or 11 when < 15% bone marrow involvement was achieved (mainly in cycles 1 or 2).

Results: Preliminary results of 14 of 44 planned patients are presented. Median age was 54 years (range 42–64). All pts had CD20+ aggressive lymphoma, 6 had relapsed aggressive lymphoma, 2 had refractory aggressive lymphoma (with PR after initial therapy) and 6 had transformed indolent lymphoma. Twelve of 14 patients were stage III/IV. The response rate to R-ESHAP was 93% (2 CR, 2 CRu, 9 PR, 1 PD). Thirteen of 14 patients proceeded to ASCT. Data on minimal residual disease in the stem cell harvest is pending. Grade 3–4 thrombocytopenia, neutropenia and anemia occurred with 53%, 31%, and 20% of R-ESHAP cycles respectively. Two of 14 patients had febrile neutropenia, one with bacteremia. Two patients had non-neutropenic bacteremia (1 with septic shock). There were no toxic deaths. Median follow-up post-ASCT is 5 months (range 1–18). Two patients progressed 4 and 5 months post-ASCT respectively. There were 3 deaths, 2 lymphoma related and 1 due to accelerated Parkinson’s Disease. Median PFS has not yet been reached.

Conclusions: This trial is still accruing patients. However, preliminary results are promising. R-ESHAP appears to be well tolerated with a high response rate. This regimen may enable more patients with relapsed/refractory aggressive lymphoma or transformed indolent lymphoma to proceed to ASCT.