Phase I/II Study of Rituxan (R) in Combination with Doxil (D) in Patients (pts) with Relapsing or Refractory B-Cell Lymphoma: Clinical Efficacy without Cardiac Toxicity.

In the past, the most common initial combination chemotherapy regimen used by most oncologists to treat B-cell lymphoma was the CHOP regimen. Although doxorubicin (DOX) is a major component of CHOP, it is associated with myelosuppression, alopecia, and potential cardiotoxicity. In vitro data has demonstrated synergistic activity between rituximab and certain drugs, including DOX. Because of D’s unique liposomal encapsulation, delivery, and toxicity profile, it may prove to be a more effective, less toxic anthracycline to combine with R. A formal Phase I/II trial to evaluate the safety and efficacy of R+D in pts with relapsing B-cell lymphoma was undertaken. R (375 mg/m²/dose) was given on day 1 and D (30 mg/m²/dose) on day 3 on q 21 day cycles for 6 cycles. Thirty-six of 42 pts have been enrolled to date. Four pts (n=3 with aggressive histologies) progressed while on treatment and did not complete the planned 6 cycles of therapy; 1 pt has not completed therapy, but is a PR mid-treatment. Demographics: 19M:17F; Median age = 63 (range 35–83); Follicular lymphoma (FL) grade 1 or 2 (n=14); FL, grade 3 (n=7); SLL (n=5); de novo DLBCL (n=3); Transformed NHL (n=6); Mantle cell lymphoma (n=1); Median number of prior treatments = 2 (range 1–8); prior anthracycline exposure (n=24; 67%). Overall, R + D was very well-tolerated. Reversible grade 3 (n=8) or grade 4 (n=4) neutropenia was seen and responded to growth factor support. Reversible grade 3 thrombocytopenia was seen in 2 pts. Of note, grade 3 palmar/plantar erythrodysesthesia occurred only in 3 pts whom were non-compliant with instructions given to avoid this side-effect associated with D therapy. Overall response rate (ITT) = 64% (42% CR, 22% PR); responses were equally distributed between both indolent and aggressive histologies. Median time-to-progression (TTP) = 12 months (range 1M to 57+M); mean TTP = 17 months. Median TTP in CRs = 14 months (range 4M to 57+M); Median TTP in PRs = 5 months (range 1M to 17M). Fifteen of 24 (63%) pts with prior anthracycline exposure demonstrated objective responses (9 CR; 6 PR). No clinical cardiac toxicity has been seen and comparison of pre-Rx to post-Rx LVEF remained >50% in all pts completing therapy. D + R immunochemotherapy is a unique, well-tolerated, non-cardiotoxic and effective salvage therapy for pts with either indolent or aggressive relapsed B-cell lymphoma. An update of the completed database will be presented at the annual ASH meeting.