Summary The marginal zone lymphomas (MZLs) are a recently defined group of related diseases that probably arise from a common cell of origin, the marginal zone B cell. Data on therapy for subtypes other than gastric mucosa‐associated lymphoid tissue (MALT) lymphoma has been largely limited to retrospective case series. This prospective phase 2 study of fludarabine and rituximab for the treatment of marginal zone lymphomas enrolled 26 patients, 14 with nodal MZL, eight with MALT lymphomas and four with splenic MZL; 81% were receiving initial systemic therapy. Only 58% [95% confidence interval (CI) 37–77%] of patients completed the planned six cycles, due to significant haematological, infectious and allergic toxicity. Four late toxic deaths occurred due to infections [15% (95% CI 4·3–35%)], two related to delayed bone marrow aplasia and two related to myelodysplastic syndrome. Nonetheless, the overall response rate was 85% (95% CI 65–96%), with 54% complete responses. The progression‐free survival at 3·1 years of follow‐up is 79·5% (95% CI 63–96%). We conclude that, although concurrent fludarabine and rituximab given at this dose and schedule is a highly effective regimen in the treatment of MZLs, the significant haematological and infectious toxicity observed both during and after therapy is prohibitive in this patient population, emphasizing the need to study MZLs as a separate entity.

SummaryToll-like receptor-9 (TLR-9) agonists have pleotropic effects on both the innate and adaptive immune systems, including increased antigen expression, enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and T helper cell type 1 shift in the immune response. We combined a TLR-9 agonist (1018 ISS, 0AE2 mg/kg sc weekly · 4 beginning day 8) with standard rituximab (375 mg/m 2 weekly · 4) in patients (n = 23) with relapsed/ refractory, histologically confirmed follicular lymphoma, and evaluated immunological changes following the combination. Treatment was welltolerated with no significant adverse events attributable to therapy. Clinical responses were observed in 48% of patients; the overall median progressionfree survival was 9 months. Biologically relevant increases in ADCC and circulating CD-3 positive T cells were observed in 35% and 39% of patients, respectively. Forty-five percent of patients had increased T cells and dendritic cells in skin biopsies of 1018 ISS injection sites 24 h post-therapy. Pre-and post-biopsies of tumour tissue demonstrated an infiltration of CD8 + T cells and macrophages following treatment. This group of patients had favourable clinical outcome despite adverse prognostic factors. This study is the first to histologically confirm perturbation of the local immune microenvironment following systemic biological therapy of follicular lymphoma.

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Eighteen patients with metastatic renal cell carcinoma, who were treated by vaccines for active specific immunotherapy, also completed skin testing with autologous tumor cells, both prior to and following vaccine treatment. All patients have now been followed for more than 5 years. Ten patients who remained skin-test-negative following treatment had no clinical responses, and all had expired by 22 months. Eight patients became skin-test-positive; three of these had clinical regressions and three remain alive after more than 69 months. The survival times of the skin-test-positive group were significantly superior to those of the skin-test-negative group. The results suggest that skin testing with autologous tumor cells may accurately identify those patients who have acquired antigen-specific cell-mediated antitumor immunity.

The combination of gemcitabine and bortezomib is a less active and more toxic regimen in relapsed HL than other currently available treatments. It poses a risk of severe liver toxicity and should be pursued with caution in other types of cancer.