We carried out a retrospective cohort study on patients with advanced cancer treated with immune checkpoint inhibitors (ICIs) to determine whether antibiotics affect treatment outcome. Sixty consecutive patients were identified, and 17 received systemic antibiotics within 2 weeks before and/or after first dose of ICI. Antibiotic-treated patients were significantly younger (p = 0.0008) and less likely to receive nivolumab (p = 0.08) or had neutrophil:lymphocyte ratio < 5 (p = 0.08). They had a lower response rate (RR) (29.4% vs 62.8%) (p = 0.024) and more inferior progression-free survival (PFS) (p = 0.048). Narrowspectrum antibiotics did not affect the RR. However, broad-spectrum antibiotics were associated with a lower RR (25% vs 61%) (p = 0.02) and a trend towards longer time to response (median: 14 weeks vs 12 weeks) (p = 0.1). They also had shorter PFS (p = 0.012). Multivariate analysis identified antibiotics as the only factor affecting RR (p = 0.0038) and PFS (p = 0.01). We next examined the 21 patients whose PFS lasted for 12 weeks or more. Five of the 21 patients received broad-spectrum antibiotics within 10 weeks before disease progression. There was a trend towards shorter PFS in these patients (p = 0.1). Finally, antibiotic-treated patients experienced shorter overall survival (OS) (median: 24 months vs 89 months) (p = 0.003). Multivariate analysis found age (p = 0.035) and antibiotics (p = 0.038) to be the only factors affecting OS. Our results point to a detrimental effect of broad-spectrum antibiotics on treatment outcome to ICI therapy.

Ranpirnase demonstrated activity and a tolerable toxicity profile in patients with unresectable MM. The prognostic value of the CALGB groups was confirmed.

IntroductionIn two clinical trials the mouse antiidiotypic monoclonal antibody (MAb) MF1 1-30, which bears the internal image of human high-molecular-weight-melanoma-associated antigen (HMW-MAA) was administered by subcutaneous route without adjuvants to patients with stage IV malignant melanoma on day 0, 7, and 28. The development of monoclonal antibodies to human tumorassociated antigens (TAA)' that meet the criteria to be used as targets for immunotherapy (for review, see 1-3) has rekindled interest in the application of immunotherapeutic approaches to malignant diseases. Among them, the use of antiidiotypic antibodies, i.e., antibodies to determinants expressed on the variable region of anti-TAA antibodies, is attracting much attention, since in animal model systems the immune response induced by this type of active specific immunotherapy is associated with an improvement of the course of the disease (4-6). The rationale underlying this approach is represented by the ability ofantiidiotypic antibodies that bear the mirror image of TAA to elicit and/or enhance anti-TAA immune responses; such responses may eventually result in the destruction of tumor cells.In order to test the usefulness of mouse antiidiotypic MAb elicited with syngeneic anti-TAA MAb to implement active specific immunotherapy, we have selected malignant melanoma as our model system for a number of reasons (7). First, a therapeutic approach based on manipulation of the patient's immune response has a potential for success in this disease because ofthe likely role of immunological factors in its pathogenesis and in its clinical course (8). Second, testing of a novel therapeutic approach finds justification in the lack of progress and limited success of available therapeutic modalities in malignant melanoma (9). Third, utilizing mouse MAb, we have identified a membrane-bound melanoma-associated antigen, referred to as HMW-MAA (high-molecular-weight-melanoma-associated antigen). This antigen represents a useful target for active and passive immunotherapy because of its high frequency in melanoma lesions, its limited heterogeneity in melanoma lesions, its high density on melanoma cells, and its restricted distribution in normal tissues (for review, see 10). Fourth, we have availability to use the mouse antiidiotypic MAb MFI 1-30 to an idiotope within the antigen-combining site of the syngeneic anti-HMW-MAA MAb 225.28. This antiidiotypic MAb bears the mirror image of HMW-MAA, because it induces anti-HMW-MAA antibodies in allogeneic and xenogeneic combinations (Chattopadhyay, P., S. V. Kaveri, J. Rosenberg, N. Byars, J. Starkey, S. Ferrone, and S. Raychadhuri. Submitted for publication.) The aim of this paper is to describe the results of two clinical trials with anti-1. Abbreviations used in this paper: HMW-MAA, high-molecularweight-melanoma-associated antigen; PBS-T20, PBS supplemented with 0.05% Tween 20; TAA, tumor-associated antigen.

Ranpirnase demonstrated activity and a tolerable toxicity profile in patients with unresectable MM. The prognostic value of the CALGB groups was confirmed.