Randomized comparison of cladribine alone or in combination with cyclophosphamide, and cyclophosphamide, vincristine and prednisone in previously untreated low‐grade B‐cell non‐Hodgkin lymphoma patients

Abstract

BACKGROUND. The objective of this study was to compare the efficacy of 3 regimens, cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination in previously untreated patients with low‐grade B‐cell non‐Hodgkin lymphoma (LGNHL). METHODS. For this 3‐arm, phase 3 study, 197 patients were randomly allocated to receive 6 monthly courses of cladribine alone, cladribine and cyclophosphamide combination, or cyclophosphamide, vincristine, and prednisone combination. Patients for whom all clinical data were available and 162 patients who completed scheduled chemotherapy were analyzed for the endpoints of this study. RESULTS. Compared with cyclophosphamide, vincristine, and prednisone combination regimen, cladribine alone or cladribine and cyclophosphamide combination induced higher probability of overall response (odds ratio [OR] = 4.0; 95% confidence interval [CI], 1.7–9,3; P = .002, and OR = 8.5; 95% CI, 3.2–22.7; P < .0001, respectively), complete remission (OR = 5.8; 95% CI, 1.8–18.5; P = .003; and OR = 14; 95% CI, 4.4–44; P < .0001, respectively), progression‐free survival (log‐rank test P < .0001), but not overall survival. After incorporating the International Prognostic Index in multivariate analysis, treatment with cladribine‐containing regimens remained an independent prognostic factor for progression‐free survival (χ2 = 35.94; hazard ratio = 2.38; P < .0002). Incidences of infections were similar in the randomized groups, whereas cladribine and cyclophosphamide combination, but not cladribine alone, induced more frequent neutropenia, anemia, and thrombocytopenia compared with cyclophosphamide, vincristine, and prednisone combination (P < .05 for each). This resulted in a higher frequency of prolongation of intervals between cladribine and cyclophosphamide combination and cyclophosphamide, vincristine, and prednisone combination cycles (P < .05), but dose reductions due to hematological or other toxicity did not differ significantly in cladribine alone, cladribine and cyclophosphamide combination, and cyclophosphamide, vincristine, and prednisone combination groups. CONCLUSIONS. For patients with LGNHL, first‐line cladribine alone or cladribine and cyclophosphamide combination regimens both provided similar treatment responses, acceptable toxicity, and better response rates than cyclophosphamide, vincristine, and prednisone combination. Cancer 2008. © 2008 American Cancer Society.

Phase I/II and pharmacokinetic study of cladribine with 2‐h infusion in Japanese patients with relapsed indolent B‐cell lymphoma mostly pretreated with rituximab

“…Several studies have indicated that cladribine, in combination with other anti‐lymphoma agents including rituximab, mitoxantrone, and etoposide, might be more effective for indolent B‐NHL than single‐agent cladribine. ( 15–17,28–31 ) To find more effective combination regimens, further studies are required.…”

“…( 7 ) Cladribine is thus distinguished from other chemotherapeutic agents by its unique characteristics, showing similar cytotoxic activity towards both dividing and resting cells. Cladribine has been found to be clinically effective for various indolent lymphoid malignancies, such as hairy cell leukemia, ( 8,9 ) chronic lymphocytic leukemia (CLL), ( 10–12 ) and indolent B‐NHL, ( 13–17 ) which are characterized by slow growth.…”

Beyond hairy cell: the activity of cladribine in other hematologic malignancies

“…The Polish Lymphoma Research Group randomly assigned 197 untreated indolent lymphoma patients to one of 3 monthly treatment arms: single-agent cladribine, cladribine plus cyclophosphamide, or cyclophosphamide, vincristine, and prednisone (CVP; Table 5). 61 Histologic subtypes by WHO classification included CLL, 35%; follicular, 28%; marginal zone, 25%; and lymphoplasmacytic, 7%. The primary endpoint was progression-free survival (PFS).…”

“…Infections occurred in 7% of patients in each arm, but grade 3 hematologic toxicity was most common in the combination cladribine and cyclophosphamide arm. 61 Cladribine has consistently demonstrated impressive activity across a wide spectrum of indolent lymphomas in untreated patients. Except for its myelosuppressive qualities, it is well tolerated and can be considered as front-line single-agent therapy in appropriate indolent lymphoma patients with a good performance status.…”

“…Indeed, cladribine was superior to CVP chemotherapy, another standard treatment, for response and survival endpoints in a study that mirrored a similar trial comparing single-agent fludarabine to CVP. 61,62 However, with the superiority of rituximab-CVP compared with CVP alone and the promising results of rituximabbendamustine, optimal front-line treatment of indolent lymphoma is in constant flux. 63 …”