A Prospective Multicenter Phase II Study by the Puget Sound Oncology Consortium (PSOC) of Gemcitabine (G), Carboplatin (C), Dexamethasone (D), and Rituximab (R) in Patients with Relapsed/Refractory Lymphoma

Abstract Combination chemotherapy remains the cornerstone of treatment for most patients with relapsed lymphoma. Unfortunately, the most frequently used salvage regimens such as ICE or DHAP often require inpatient hospitalization for administration and must be used with caution in the elderly, frail, or those with comorbidities. In order to develop a safe, effective, outpatient salvage therapy for the treatment of lymphoma, PSOC prospectively evaluated 2–4 cycles of the novel regimen GCD±R. Eligibility criteria included: age ≥18 yrs, measurable relapsed/refractory disease, no active CNS disease, PS 22, ANC ≥1500/μl, platelets ≥100k/μl, bili/Cr <2x ULN, and no platinum refractory disease. Therapy included G 1000 mg/m2 days(d) 1 and 8, C AUC =5 d 1, D 40 mg daily d 1–4, and R (for patients with CD20+ tumors) 375 mg/m2 d 8 (cycled every 21 days). G-CSF use was at the discretion of the treating physician. Patients without disease progression after 2 cycles could continue up to a total of 4 cycles. Fifty-five patients were enrolled and 51 were evaluable for response (primary endpoint). Baseline characteristics (n =51) included: median age 58 (range 19–79), female 21 (41%), stage III/IV 45 (88%), elevated LDH 17 (33%), median # prior therapies 2 (range 1–8), prior anthracycline 43 (84%), prior platinum 7 (14%), prior high-dose therapy (HDT) and stem cell transplant (SCT) 6 (12%). In addition, 88% of patients with CD20-expressing tumors had received prior R. Histologies included classical Hodgkin lymphoma (HL) = 14, follicular lymphoma (FL) =11, diffuse large B-cell lymphoma (DLBCL) = 8, mantle cell lymphoma (MCL) = 7, marginal zone lymphoma (MZL) = 4, small lymphocytic lymphoma (SLL) = 3, Peripheral T-cell lymphoma (PTCL) = 3, and lymphoplasmacytic lymphoma (LPL) = 1. The overall response rate (ORR) was 67%, with 31% achieving a CR/CRu. In addition, 4 of 7 (57%) patients relapsing after platinum-based chemotherapy, and 4 of 6 (67%) patients relapsing after HDT and SCT achieved a CR/CRu. The table summarizes response rates by histology. Peripheral blood stem cells were successfully mobilized in all 17 (100%) patients in whom this intervention was attempted following GCD±R and G-CSF (median yield of 10.9 × 106 CD34+ cells/kg; range, 5.0–24.1 × 106) with a median time to first apheresis of 14d after initiating chemotherapy (range, 11–19d). Despite 43% and 67% of patients developing grade 4 neutropenia and thrombocytopenia (CTCAE 3.0), rates of ≥grade 3 febrile neutropenia (8%), infection (16%), and bleeding (8%) were acceptable. Other most common non-hematologic toxicities of ≥grade 3 included laboratory (22%) and cardiovascular (16%). There were no treatment-related deaths. With a median follow up of 12 months, 35 (68%) patients are alive and 22 (43%) are progression-free. In this prospective multicenter trial we demonstrate that GCD(R) is a safe and effective outpatient regimen for the treatment of relapsed lymphoma, with particular efficacy in HL, FL, MCL, and MZL (all >70% ORR) and can successfully mobilize PBSC. These results provide an additional, outpatient-based therapeutic option for such patients and set the stage for future randomized trials directly comparing salvage regimens for lymphoma. Table: Response rates by histology Histology n Overall Response (%) CR/CRu (%) HL 14 12 (86) 7 (50) FL 11 9 (82) 4 (36) DLBCL 8 5 (63) 1 (13) MCL 7 5 (71) 3 (43) MZL 4 3 (75) 1 (25) PTCL 3 0 (0) 0 (0) SLL 3 0 (0) 0(0) LPL 1 0 (0) 0(0) Total 51 34 (67) 16 (31)

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