Superior Survival Outcome of Blinatumomab Compared to Mitoxantrone-Etoposide-Cytarabine Salvage for Adult Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia: A Propensity Score-Matched Cohort Analysis

Background: Complete remission (CR) rate and long-term overall survival (OS) is very poor in patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). Previous clinical trials revealed a good remission rate and a safe bridging role to allogeneic-HCT compared to various standard treatments, and several real-world data have been reported. Aim: Here, we analyzed outcome of blinatumomab versus our conventional intensive chemotherapy by propensity score-matched analysis. Methods: From 2009 to 2020, 197 consecutive R/R BCP-ALL were treated with mitoxantrone-etoposide-cytarabine (MEC, n=113) or blinatumomab (n=84), and allogeneic-HCT was planned in patients with CR. For propensity score-matching, the MEC and blinatumomab cohorts were matched in a 1:1 ratio using 5 criteria of age < 35 years old, short CR duration < 12 months, adverse-risk karyotype including Ph-chromosome at relapse, previous allogeneic-HCT, and first-line salvage or not. We compared CR rate, regiment related mortality, and OS with cumulative incidence of relapse (CIR) and non-relapse mortality (NRM). Results: Matched cohort consisted of 52 patients for each salvage group and matched criteria were the same exactly. Median age was 42 years and 34 (65.4%) patients were > 35 years old. There were 22 (42.3%) primary refractoriness, 9 (17.3%) post-chemotherapy relapse and 21 (40.4%) post-HCT relapse. Among 30 relapsed patients, 19 (63.3%) were early relapse with CR duration less than 12 months. There were 25 (48.1%) with poor-risk karyotype at relapse of which 10 were Philadelphia-chromosome. Extramedullary relapse was observed in 14 (26.9%) and 8 (15.4%) were advanced-line salvage. CR rate was significantly higher in blinatumomab (78.8% vs. 53.8%, p=0.012) and more patients proceeded to allo-HCT (80.8% vs. 46.2%, p<0.001). Regimen-related mortality was significantly higher in MEC (40.4% vs. 1.9%, p<0.001). After median follow-up of 32.5 months (range 6.2 to 131.2), 3-year OS of blinatumomab and MEC was 33.2% and 15.4% (p<0.001), and 3-year NRM was 30.3% and 51.9% (p=0.004), respectively. After CR achievement, CIR was not significantly different (46.9% vs. 60.0%). In multivariate analysis, CR duration < 12 months was related with poor OS with high CIR. MEC regimen showed poor OS with high NRM. High NRM was also related with advanced-line salvage. Conclusion: Our matched cohort analysis clearly showed that blinatumomab is superior to MEC salvage regimen. However, we are observing relapse in up to 50% after blinatumomab and following allo-HCT still shows high NRM. Further combinatorial using novel therapeutics are needed for R/R BCP-ALL. Figure 1 Figure 1. Disclosures Kim: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AIMS Biosciense: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; AML-Hub: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BL & H: Research Funding; BMS & Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boryung Pharm Co.: Consultancy; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Consultancy, Honoraria; LG Chem: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Pintherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Speakers Bureau; SL VaxiGen: Consultancy, Honoraria; VigenCell: Consultancy, Honoraria. Lee: Alexion, AstraZeneca Rare Disease: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Immunotherapy Discontinuation in Metastatic Melanoma: Lessons from Real-Life Clinical Experience

Background: Immunotherapy has revolutionized outcomes for melanoma patients, by significantly prolonging survival and probably even curing a fraction of metastatic patients. In daily practice, treatment for responding patients is often discontinued due to treatment-limiting toxicity, or electively, following a major tumor response. To date, the criteria for a safe stop and the optimal duration of treatment remain unclear. Patients and methods: This is a real-world single-site cohort of 106 advanced melanoma patients who were treated with immunotherapy and who discontinued treatments in the absence of disease progression. Here, we describe their long-term outcomes, and analyze the differential characteristics between patients who ultimately experienced progression and those who remained in unmaintained durable response. Results: Patients were treated with anti-PD-1 monotherapy (81%) or in combination with ipilimumab (19%) for a median of 15.2 m (range, 0.7–42.3 m). Upon discontinuation, 75.5% had achieved a complete response (CR). After a median follow-up of 20.8 m (range, 6–58) from discontinuation, 32% experienced disease progression. Median time to progression was 8.5 m (range, 1.5–37). Response to re-induction with anti-PD-1 was observed in 47%. On multivariate analysis, achieving a non-CR response, immunotherapy given in advanced line, and shorter treatment duration were significantly associated with lesser progression-free survival. Conclusions: This is one of the few reports on real-world melanoma patients who discontinued immunotherapy while responding to treatment. This study reveals the key factors to bear in mind when considering an elective treatment cessation. Specifically, patients with non-CR as best response and patients treated in an advanced-line setting should be treated for longer periods, and elective discontinuation should not take place prior to 18 m.

Description of new high yielding forage Avena Sativa L. cultivar ‘Super Green Oats’

Oat [Avena sativa (L.)] cultivar “Super Green Oats” was developed through conventional breeding methods by the Fodder Research Institute, Sargodha, and released as general cultivar in 2020. Commercial cultivar is an advanced line of “FRI-03” which is derived from cross of parental accessions (No. 668 × No. 632) and subsequent selections in various segregating populations (F2 - F6), through pedigree methods having uniformity > 99%. Cultivar had 9% and 15% forage yield advantage over commercial check “Sargodha-Oat 2011” during 2014 and 2015 station trials while it gave 9% higher fodder yield during 2016-17 during zonal trials over commercial check.. It is green, tall, multi-tillering, with slight later in maturing cultivar and produce light brown seed. It has many desirable forage quality traits, including high palatability (82%), protein content (10%) and had resistance to biotic and abiotic stresses. It flower about 10 days later than standard check variety. Moreover, it has higher stability (coefficient of regression bi = 1.06) calculated over 3 environments for 2 years. Its robust yield combine with high palatability and high protein contents than standard check and resistance to biotic and abiotic stress show that Super Green Oat will be highly useful cultivars in both irrigated and arid region of Punjab Province. Moreover, the cultivar will be potential parent for the development of new pedigrees for the genetic improvement of oat germplasm.

Study of principal component analyses for pod traits in soybean

Yield being a complex entity influenced by several components and environments. PCA is a well-known method of dimension reduction that can be used to reduce a large set of variables to a small set that still contains most of the information in the large set (Massay, 1965 and Jolliffie, 1986). In present study, PCA preformed for pod and yield traits revealed that out of fourteen, only five principal components (PCs) exhibited more than 1.0 eigen value and showed about 70.44% total variability among the traits. PC1 showed 23.83% variability with eigen value 3.33 indicating the maximum variation in comparison to other four PCs. The PC1 was more related to traits viz., days to 50% flowering, total number of pods per plant, number of seeds per plant, biological yield per plant and seed yield per plant. Thus, PC1 allowed for simultaneous selection of yield related traits and it can be regarded as yield factor. PC2 exhibited positive effect for days to maturity, number of primary branches per plant and number of nodes per plant, The PC3 was more related to number of two seeded pods per plant, 100 seed weight and harvest index traits, whereas PC4 was more loaded with three seeded pods per plant. PC5 was more related to plant height and number of one seeded pods per plant. A high value of PC score of a particular advanced line in a particular PC denotes high value for those variables. Genotypes namely KS 103, JS 20-15, PS 1423, Cat 1957, Cat 1958, JS 20-06 and JS 20-66 can be considered an ideotype breeding material for selection and for further utilization in precise breeding programme.

Assessment of High-yielding Rapeseed-mustard Varieties in Haor (Wetland) Ecosystem for Development of Mustard-Boro Rice-Fallow Pattern in Sylhet Region of Bangladesh

Aims: To assess the suitability of short duration high yielding rapeseed-mustard variety(s) cultivation in the haor (wetland) areas. Study Design: Randomized complete block (RCB). Place and Duration of Study: Farmers’ field of Lalakhal, Jaintapur Upazila of Sylhet, Bangladesh during November 2014 to February 2015. Methodology: The treatments included in the experiment were seven rapeseed-mustard varieties viz. i. Tori-7, ii. BARI sarisha-13, iii. BARI sarisha-14, iv. BARI sarisha-15, v. BARI sarisha-16, vi. advanced line Nap-205 and vii. BINA sarisha-4. Design of the experiment was randomized complete block (RCB) with three replications. Results: The results revealed that BARI sarisha-16 produced the highest seed yield (1.99 t ha-1), but it took the maximum days (92) to maturity. The variety BARI sarisha-15 produced the second highest seed yield (1.78 t ha-1) closely followed by BINA sarisha-4 (1.75 t ha-1) and BARI sarisha-13 (1.68 t ha-1). The lowest seed yield (1.53 t ha-1) was obtained from the variety Tori-7 which was statistically similar to that of BARI sarisha-14 (1.59 t ha-1) and Nap-205 (1.68 t ha-1). Tori-7 took the minimum days (74.7) to maturity while BARI sarisha-15 took 77.7 days. Conclusion: Variety BARI sarisha-15 could be a good option for haor areas for cultivation in medium low land before Boro rice after recession of rainwater, as it took less duration to maturity (77.7 days) with good seed yield (1.78 t ha-1).

Response of peanut (Arachis hypogaea L.) genotypes to smut (Thecaphora frezii) in the peanut growing region of Argentina

Genetic resistance is the most efficient tool in crop disease management. Peanut smut is currently one of most important peanut diseases, with its incidence increasing in terms of both damage level and crop area covered. The aim of this study was to assess the response of different genotypes obtained by the Facultad de Agronomía y Veterinaria of the Universidad Nacional de Río Cuarto (Argentina) to smut and their yield. During the 2016/17, 2017/18 and 2018/19 crop seasons, three experimental assays were conducted in General Deheza (Córdoba province, Argentina) to evaluate the varieties Uchaima, Utré and Mapu, the advanced lines LAx-1, LAx-2, LAx-3 and LAx-4, and the cultivar Granoleico, which was used as susceptible control. Final incidence and severity of peanut smut, as well as kernel yield, were evaluated. The variety Utré and the advanced line LAx-1 exhibited the best response to smut over the three crop seasons, without differences between them, but differing significantly from the remaining genotypes. Both genotypes showed incidence below 6.8% and severity below 0.21. In the 2016/17 crop season, LAx-1 had the highest kernel yield (3791.6 kg/ha). In the 2017/18 and 2018/19 crop seasons, Utré had the highest yield (1065 and 3975 kg/ha). Kernel yield of susceptible genotypes was below 2851.6 kg/ha in the 2016/17 and 2018/19 crop seasons, and below 805 kg/ha in the 2017/18 crop season. Genotypes LAx1 and Utré are resistant to peanut smut. This is the first report of a peanut commercial variety developed in Argentina (Utré) with confirmed tolerance to smut.

Zinc Enriched High Yielding Rice Variety BRRI dhan84 for Dry Season Rice Growing Areas of Bangladesh

A newly released zinc enriched, high yielding, slender and red pericarp grain containing rice variety BRRI dhan84, suitable for dry ecosystem (Boro season) of Bangladesh is an improvement over existing zinc enriched rice varieties for Bangladesh. The main objective of this research was to develop the of high yielding rice varieties with improved nutritional quality in term of high zinc (Zn≥24 mg/kg) in polished grain. The study was taken in 2004 by crossing between BRRIdhan29/IR68144//BRRI dhan28///BR11 and it takes near about 13 years to develop the targeted variety. After selection of one homozygous advanced line (BR7831-59-1-1-4-5-1-9-P1) the Regional Yield Trial (RYT) was conducted in Boro 2014-15 saeson and the Advanced Line Adaptive Research Trial (ALART) was evaluated at different farmers’ field in Boro 2015-16 season and different yield trials were conducted using Randomized Complete Block Desing (RCBD). The variety has satisfactorily passed the Proposed Variety Trial (PVT) conducted in the farmers’ field in Boro 2016-17 season. As a result National Seed Board (NSB) approved this variety for commercial cultivation in the dry season (Boro season) in 2017. It has modern plant type with 96 cm plant height and matures by 140 days. The salient feature of this variety is the red colored grain, earlier than check variety, the proposed variety showed higher yield than check variety BRRI dhan28. Identifying characters of this variety are dark green leaf, semi erect flag leaf, long slender and red colored grain. It can produce 6.0-6.5 t/ha grain yield. Thousand grain weight of the variety is 22.8 g and it has colored grain tip. The rice has zinc content 27.6 mg/kg, 25.9% amylose content with 9.7% protein content. BRRI dhan84 was released as a high yielding, zinc enriched rice variety to meet the nutritional (zinc) demand of the country. The zinc enriched BRRI dhan84 is a superb variety for cultivating in the dry (Boro) season and farmers can be economically benefited and the country will be nutritionally benefited by the cultivation of BRRI dhan84.

Agroclimatic Indices of Rice (Oryza sativa L.) Influenced by Different Planting Times

Meteorological variables have an important role in rice production. Considering this study was carried out in Aman season of 2016 at the research field of Bangladesh Rice Research Institute, Gazipur. The research was conducted in order to investigate the effects of planting time on various agrometeorological indices viz., accumulated growing degree days (GDD), heliothermal units (HTU), photo thermal units (PTU), and heat use efficiency (HUE) the yield of advanced/variety grown under different time of transplanting in the Gazipur climatic zone (AEZ, 28). The research was conducted as a split plot using randomized complete block design (RCBD) with three replications. In this research, three planting times (1st Aug, 16th Aug, and 31th Aug) and the Advanced lines/varieties BR (Bio) 9786-BC2-119-1-1, BR (Bio) 9786-BC2-132-1-3 and BRRI dhan49 (check variety) were used in the experiment. The results showed that planting time significantly affected on grain yield. Among the genotypes, BR (Bio) 9786-BC2-119-1-1 and BR (Bio) 9786-BC2-132-1-3 produced significantly higher grain yield than check variety BRRI dhan49 in all the planting times. The variety (BRRI dhan49), transplanted at the first August, took maximum calendar days (136 days) to attain different phenological stages till physiological maturity coupled with highest growing degree days (2420 degree day) for maturity, lowest heat use efficiency (2.25 kg ha-1 c-1 day-1), highest heliothermal units (15141.01 degree day hours) and lowest photothermal units (29678.81 degree day hours) resulting lower yield. Among the advanced lines the line BR (Bio) 9786-BC2-119-1-1 took higher calendar day (134 days) to attain different phenological stages till physiological maturity coupled with higher growing degree days (2393 degree day) for maturity, heat use efficiency (2.76 kg ha-1 c-1 day-1), heliothermal units (13759.75 degree day hours) and photothermal units (30112.51 degree day hours) resulting higher yield. Taken together, the results indicate that the advanced line, BR (Bio) 9786-BC2-119-1-1, could be select as a best advanced line to release as a variety due to its higher grain yield. Bangladesh Rice j. 2019, 23(2): 87-94