Abstract: New Zealand pastures largely comprising Lolium ryegrass species (Poales: Poaceae) are worth $19.6B and are subject to major pest impacts. A very severe pest is the Argentine stem weevil Listronotus bonariensis (Kuschel) (Coleoptera: Curculionidae). This has been previously suppressed by the importation biological control agent, Microctonus hyperodae Loan (Hymenoptera: Braconidae). However, this suppression has recently declined and is subject to investigation. It has been hypothesised that grass type influences the parasitism avoidance behaviour by the weevil and thus parasitism rates. This study explored the hypothesis using three common pasture grasses: a diploid Lolium perenne x Lolium multiflorum hybrid ryegrass (cv. Manawa), a tetraploid Italian ryegrass L. multiflorum Lam. (cv. Tama), and a diploid perennial ryegrass L. perenne L. (cv. Samson). The described laboratory-based microcosm methodology determined the extent of weevil avoidance behaviour on each of these three grasses when subjected to the parasitoid. Such reaction was gauged by the extent of reduced weevil on-plant presence and feeding compared to the control populations. In the absence of the parasitoid, the hybrid cv. Manawa ryegrass is as highly favoured by the weevil as the tetraploid cv. Tama. On diploid cv. Samson, feeding is considerably less. In the presence of the parasitoid, weevils on the tetraploid cv. Tama plants showed little avoidance activity in response to the parasitoid and it can be argued that the benefits of staying on this plant outweighed the possibility of parasitism. Conversely and surprisingly, in the parasitoid’s presence, weevils on diploid cv. Manawa showed very strong avoidance behaviour leading to levels of exposure similar to those found on the less-preferred diploid cv. Samson. These findings reflect how weevil parasitism rates have declined in most Lolium grasses, particularly diploids, since the 1990s, but not in the tetraploid L. multiflorum . This contribution supports the hypothesis that the decline in weevil parasitism rates has been the result of rapid evolution arising from parasitoid-induced selection pressure and the countervailing effect of the nutritional quality of the host plants.

Abstract: Paropsis charybdis (Coleoptera: Chrysomelidae) has been a major pest of Eucalyptus spp. since invading New Zealand from Australia over 100 years ago. Here, we report on the phenology, egg parasitism and defoliation levels of P. charybdis at two Eucalyptus nitens plantations in the central North Island of New Zealand and assess the establishment prospects and potential impact of a new biological control agent, the larval parasitoid Eadya daenerys . Field monitoring found that 90–100% of first generation P. charybdis eggs emerged, showing that the existing egg parasitoids Enoggera nassaui (Hymenoptera: Braconidae) and Neopolycystus insectifurax (Hymenoptera: Pteromalidae) are ineffective at controlling this generation. Further field monitoring revealed effective control of second generation eggs by E. nassaui and N. insectifurax despite the presence of Baeoanusia albifunicle (Hymenoptera: Encyrtidae), a hyperparasitoid of E. nassaui . Phenology data show that first generation P. charybdis larvae will likely be synchronous with the adult emergence of E. daenerys (Hymenoptera: Braconidae) the new larval endoparasitoid proposed to be introduced from Australia. Climate matching predicts E. daenerys could establish in all areas of New Zealand where P. charybdis impacted Eucalyptus spp. plantations are grown. The addition of a larval endoparasitoid could significantly contribute to the suppression of P. charybdis by decreasing first generation larval survival.

Abstract: Biological control of pests continues to become more important in agriculture as pesticides are being withdrawn. However, successful control can be compromised by contemporary evolution. Recent work in New Zealand has shown that the once-successful biological control programme of the sexually reproducing grassland weevil pest Listronotus bonariensis by the asexual parasitoid Microctonus hyperodae has now failed. To explain the mechanisms associated with this, weevil parasitism rates were intensively monitored between 1994 and 2019. Frequent sampling took place at widely dispersed New Zealand sites spanning the warmer northern regions to the cooler south. Based on elapsed heat accumulation above the parasitoid’s development temperature threshold of 10.2°C degree-day (DD), the results over c. 25 years indicated that the extent of parasitism decline at a given location was directly related to the accumulated DD. The latter, in turn, was taken to be indicative of parasitoid activity and selection pressure. Accordingly, laboratory microcosm experiments measuring the response of weevils collected from the North–South distribution to a common population of parasitoids showed that the weevils from the warmer northern region showed higher rates of avoidance of the searching parasitoids than those from the cooler south. This strongly supported the hypothesis that the weevil resistance mechanism is related to levels of parasitoid avoidance behaviour arising from long-term parasitoid selection pressure. This study of the behaviourally based acquisition of resistance to a biological control agent illustrates a general need to consider the potential capability of an exotic target host to develop resistance to imported biological control agents. This includes identifying existing host adaptations that selection pressure could potentially act upon that may compromise otherwise successful biological control programmes. Such a requirement points to the need for long-term monitoring of biological control systems and understanding of parasitoid/host dynamics.

Abstract: Background: Mantle cell lymphoma (MCL) remains challenging particularly in the relapsed/refractory setting, where patients often show chemoresistance. Novel molecular-based therapies have shown impressive and durable activity in that setting, although primary and acquired resistance remains problematic. A recent retrospective series of 114 patients who had failed ibrutinib (median of 4.7 month exposure) showed very short median overall survival of 2.9 months after ibrutinib cessation (Martin et al. Blood 2015). Here we report the results from the observationalMCL-004 study investigating outcomes of patients treated with lenalidomide (an IMiD® immunomodulatory agent) after failing ibrutinib; patients were either relapsed, progressed, refractory, or intolerant to ibrutinib. The objective here is to evaluate the clinical effectiveness of lenalidomide monotherapy or a lenalidomide-containing regimen in relapsed/refractory MCL after ibrutinib failure or intolerance. Methods: MCL-004 is a multicenter study in patients with MCL who relapsed/progressed after or were refractory/intolerant to ibrutinib, and were subsequently treated with lenalidomide. With patient informed consent, data were collected retrospectively from patients who, after their disease failed to respond to ibrutinib, received lenalidomide-based therapy from March 1, 2009 to June 9, 2015. The primary endpoint was investigator-assessed overall response rate (ORR) based on 2007 International Working Group criteria, with required patient monitoring and routine imaging. Results: Thirty patients were enrolled at 7 US sites and 1 EU site, including patients receiving lenalidomide monotherapy (n=8), lenalidomide + rituximab (n=8), and lenalidomide + other treatment (n=14). Lenalidomide + other treatment included combination with rituximab, carfilzomib, and dexamethasone (n=3); other combinations were given in ≤2 patients. Patients had a median age of 69 years (range, 50-84), and median time from last dose of ibrutinib to first dose of lenalidomide was 1.3 weeks (range, 0.1-21.7). All patients received ≥2 prior lines of therapy, and 83% received ≥3 prior therapies (median prior therapies, 3.5; range, 2-8). With prior ibrutinib, the best responses achieved were 10% complete response (CR), 43% partial response (PR), 3% stable disease, 40% relapse/progressive disease (PD), and 3% unknown. Primary reasons for ibrutinib discontinuation were 50% relapse/PD, 40% refractory, and 10% intolerance. Patients received a median of 2 cycles (range, 1-11) of lenalidomide-based treatment. Eight patients' disease responded (4 CR, 4 PR), resulting in an ORR of 27% (95% CI, 12%-46%). Five of 8 maintained their response at data cut-off (3 CR, 2 PR). ORR was similar for patients with relapse/PD vs. those refractory to ibrutinib (29% vs. 33%, respectively). Median duration of response (DOR) was 18 weeks (95% CI, 2.9-25+) for all patients. Median DOR was not reached in patients who previously relapsed/progressed with ibrutinib compared with a median of 11 weeks for those whose disease was refractory to ibrutinib. Most common treatment-emergent adverse events (TEAEs) were 33% fatigue; 27% nausea; and 23% each dyspnea, neutropenia, dizziness, or rash. In general, TEAEs were less common with lenalidomide monotherapy. The most frequently reported serious AEs were pneumonia, dyspnea, deep vein thrombosis, hypotension, and acute kidney injury (7% each). At data cutoff, 15 patients (50%) had died, mostly due to MCL and none due to second primary malignancy. Conclusions: Most patients received ≥3 prior lines of treatment, and median time from last dose of ibrutinib to first dose of lenalidomide was short. Lenalidomide-based treatment showed clinical activity in this difficult-to-treat patient population, including 27% ORR and 13% CR. No new safety signals for lenalidomide were identified. Overall, our results show that lenalidomide is active in a selected group of patients with relapsed/refractory MCL that previously failed ibrutinib. Disclosures Wang: BeiGene: Research Funding; Asana BioSciences: Research Funding; Acerta Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Kite Pharma: Research Funding; Juno Therapeutics: Research Funding; Onyx: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Martin:Acerta: Consultancy; Teva: Research Funding; Novartis: Consultancy; Janssen: Consultancy, Honoraria, Other: travel, accommodations, expenses; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Other: travel, accommodations, expenses. Goy:Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Writing support, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding; Johnson & Johnson: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Hamadani:Takeda: Research Funding. Ghosh:Gilead: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; SGN: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Genentech: Research Funding; TG Therapeutics: Research Funding. Reeder:Millennium: Research Funding; BMS: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Barnett:Celgene Corporation: Employment, Equity Ownership. Casadebaig Bravo:Celgene: Employment, Equity Ownership. Schuster:Pharmacyclics: Consultancy, Research Funding; Novartis: Research Funding; Gilead: Research Funding; Janssen Research & Development: Research Funding; Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Research Funding; Genentech: Consultancy; Hoffman-LaRoche: Research Funding.