13 results on '"Rudolph Valentino"'
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2. A rare Philippine plant found again after almost a century: the rediscovery and lectotypification of Acranthera philippinensis (Rubiaceae)
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JORGE ANTON D. ORDAS, SARAH GRACE S. ZAMUDIO, and RUDOLPH VALENTINO A. DOCOT
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Plant Science ,Ecology, Evolution, Behavior and Systematics - Abstract
A floristic excursion in Zamboanga del Sur, Philippines led to the rediscovery of Acranthera philippinensis, an endemic Rubiaceous taxon with very limited information since 1905. This study provided a detailed description, a color plate, a distribution map of A. philippinensis, and information on its habitat and phenology. Based on the IUCN guidelines, A. philippinensis is provisionally categorized as Endangered (EN). In addition, a lectotype is also designated for this name. The findings of this study demonstrate the urgent need for more botanical research to be conducted in the Philippines, where numerous species await recollection and discovery.
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- 2023
3. The The ginger genus Burbidgea confirmed in the flora of the Philippines
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Kean Roe F. Mazo, Rudolph Valentino A. Docot, and Axel Dalberg Poulsen
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Ecology ,Plant Science ,Ecology, Evolution, Behavior and Systematics - Abstract
The facultative epiphytic ginger genus Burbidgea harbours six species hitherto thought to be endemic in Borneo. Recent fieldwork in Zamboanga region, Mindanao, Philippines, resulted in the collection of a ginger, which we identified as Burbidgea nitida. The species, however, was already collected in Zamboanga region in 1919 but the evidence remained misidentified for a long time as Hedychium. Including the Burbidgea in the flora of the Philippines, increases the number of native ginger genera of the country to 17. Based on the recent collections, a complete description of B. nitida in the Philippines is provided here including illustrations and notes on ecology and a local name. We lectotypify Burbidgea nitida, the type of the genus, and clarify the overlap of native ginger genera and species between Borneo and Philippines.
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- 2022
4. Corybas hamiguitanensis Tandang, Galindon & R. Bustam. 2023, sp. nov
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Tandang, Danilo N., Docot, Rudolph Valentino A., Galindon, John Michael, Jr, Tomas Reyes, Tadiosa, Edwin R., Tandang, Sue Dixie A., Moran, Cecilia B., and Bustamante, Rene Alfred Anton
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Tracheophyta ,Corybas ,Liliopsida ,Asparagales ,Corybas hamiguitanensis ,Biodiversity ,Plantae ,Orchidaceae ,Taxonomy - Abstract
Corybas hamiguitanensis Tandang, Galindon & R.Bustam. sp. nov. (Fig. 1–3) Type: — PHILIPPINES. Mindanao Island: Davao Oriental Province, San Isidro Municipality, La Union Barangay, Mount Hamiguitan Range Wildlife Sanctuary, 1134 m a.s.l., July 2016, Tandang 2061 (holotype PNH!, isotypes CAHUP!, CMUH!). Description:— Corybas hamiguitanensis resembles C. gibbifer Schlechter (1923: 21), but is distinct by having leaves with whitish-green midrib and veins (vs. entirely dark green lamina), absence of a boss on the limb of the labellum (vs. presence), and with more nerves on the margin of the labellum (27 nerves vs. 12 nerves). A more detailed comparison of character are presented in Table 1. Small terrestrial herbs, 15.2–24(–37.2) mm tall from underground tuber to the flower tip, solitary or forming a small colony of 2 to less than 10 individuals, individual plants the roots are covered with mycorrhizal fungal threads. Roots terete, succulent, usually stout near the root collar, 10.3–15.2 mm long, minutely pilose becoming narrow and sparsely hairy towards the tip, 1.5–1.7 mm wide at widest part to 0.5–1.0 mm wide at the tip. Tuberoids underground, lightbrown, globose, 4.7–6.4 × 5.2–5.8 mm, villose, minutely covered with brown hairs. Stem solitary arising from the subterranean tuber, erect, white to yellowish, longitudinally channelled at the abaxial side, glabrous, 4.8–32.6 × 0.7–1.1 mm, protected at base by a persistent short, fleshy tubular sheath. Cataphyll 3.1–6.9 mm long, shortly tubular, 0.4–1.6 × 1.2–1.5 mm, with short triangular expanded upper part, 2.5–2.8 mm wide when expanded, glabrous, 1-nerved, pale green at the midrib and near apex, the apex acuminate. Leaves sessile, glabrous, young leaves dark green, cordate with white midrib and whitish veins to rarely pink; matured leaves with flower, broadly cordate, upper surface light to dark green, dull, contrasting with whitish-green veins or sometimes with inconspicuous pinkish veins, 11.4–16.3 mm long from leaf attachment to tip, to 15.2–21.4 mm from basal lobes to tip, blade 13.9–18.3 at widest point, base cordate, decurrent towards the stem, margin white, slightly to conspicuously undulate, apex acute to acuminate, acumen 0.5–1.4 mm. Veins glabrous, the midrib is straight from base to tip, impressed at the upper surface, raised below with 2 to rarely 3 pairs of primary veins on both sides, inner one usually extending into near midvein tip, middle pairs arching from half up to near tip before connecting with inner nerve, outer nerves usually very short, lateral nerves subopposite to alternate, 4 =or 7 on either side of the midrib, branching, lateral nerves on the two inner veins, 4 to 10, not branching. Floral bract, white at base to whitish green at the upper half, basal portion clasped at the ovary and becoming spreading, concave, lanceolate-triangular to narrowly linear-lanceolate when flattened 2.7–4.9 × 0.7–1.4 mm, with scattered white raphides, margin minutely crenulate, acuminate at tip. Flower 10.3–12.0 mm high (including ovary). Peduncle pale green, terete, glabrous, almost sessile, 0.6–1.4 × 0.5–1.1 mm. Ovary light brown to pink, cylindrical, 4–ribbed, 2.6–5.4 × 1–1.8 mm, slightly twisted to consistently strongly recurved making the flower facing upward position on the ground. Median sepal cucullate, exceeding and arching over the labellum, fleshy and thick, abaxial surface at basal half flecked with purple line in both side of the midvein becoming completely white at the upper part, adaxial white, purple at the upper part near apex, apex white, 16.5–21 mm long, when flattened, narrow at base, 1.5–1.9 mm wide, gradually widening at the middle, 4–5.5 mm and obovate-spathulate at the apical part, 7.2–9.1 mm, 3-veined at base, diverging into 9 or 10 at tip, margin translucent, entire to slightly minutely crenulate at the apex, apex warty at abaxial part, mucronate or apiculate with acumen 0.5–0.8 × 0.7–0.9 mm. Lateral sepals and petals, light pink, different in size, hidden behind the labellum, cuculate. Lateral sepals linear, strongly curved, 2.4–5.7 long, 0.5–0.7 mm wide at base, middle 0.2–0.4 mm wide, narrow at apical part 0.1–0.2 mm wide, margin entire, acuminate at the apex. Petals linear, shorter than the sepals, 1.3–1.8 mm long × 0.3–0.6 mm wide at base. Labellum from tubular basal part, 2.7–5.4 mm long, 3.9–4.3 mm in diameter, curving upwards and opening into a orbicular limb, 12.7–13.6 mm long, 12.5–13.1 mm wide when flattened out, reniform in shape when flattened, coarsely papillose throughout, with a distinct ovate shaped patch with echinate projections at the apical part, margin minutely toothed in distal half, becoming fimbriate towards the tip, lacerations 0.7–1.7 mm long, 0.08–0.2 mm wide, almost entirely black, with a bright magenta patch, margin white to bright magenta, 27-nerved. Paired spur white with short black line at the basal middle part on abaxial sides, conical, 1.7–3.1 × 0.8–1.7 mm. Column 2.9–3.2 mm long (including the anther cap and ventral pad). Anther cap cordate, 1.2–1.3 × 1.4–1.6 mm when flattened, central apiculum shorter than the two anther cap lobes. Stigma orbicular, 0.5 mm in height by 0.7–0.9 mm wide; ventral pad, trilobed, 1.4–1.5 × 0.9–1.4 × 1–1.7 mm. Etymology:— The epithet “ hamiguitanensis ” refers to the type locality of this species which is Mt. Hamiguitan. Phenology:— The species flowers during June to August. Distribution and ecology:— In our continuous botanical survey, Corybas hamiguitanensis is found growing either solitary, or in a small group in eight sites at different elevations ranging between 626–1279 m a.s.l. within MHRWS. In small colonies, most of the plants are juvenile with one to two flowering individuals observed and collected during the visit. This species occupies various habitats from drier conditions to partly-shaded under lowland evergreen rainforest. Occasionally, their stems are buried in thick wet forest litters, growing with mosses within the forest over ultramafic rocks and or at the base of moist boulders in deep shaded environments within the mossy forest. Proposed conservation assessment:—During the 2016 and 2019 surveys, C. hamiguitanensis was found in eight locations inhabiting different altitudinal gradients of different forest types from lowland evergreen rainforest, forest over ultramafic rocks, and mossy forest of Mount Hamiguitan Range Wildlife Sanctuary. However, a thorough population survey is needed because not enough data on its population of the species has been collected. We recommend the category of Data Deficient (DD). Notes:— Corybas hamiguitanensis resembles C. gibbifer in having lanceolate bracts; warty, cucullate, obovate-spathulate dorsal sepal; with 3-nerves at the base and 9-nerves on the hood. The dorsal sepals of both species fall within a 15–25 mm long range. However, C. hamiguitanensis can be distinguished by its leaf with whitish-green midrib and veins (vs. entirely dark green lamina). Additionally, the peduncle of C. hamiguitanensis is longer at 0.6–1.4 mm (vs. 0.5 mm or none), having a shorter and narrower bract at 2.7–4.9 × 0.7–1.4 mm (vs. 4–10 × 2 mm), a strongly recurved ovary that is longer and narrower at 2.6–5.4 × 1–1.8 (vs. 4–7 × 3), and the shorter lateral petal 1.3–1.8 mm long (vs. 5.5–13 mm long). Furthermore, the labellum of C. hamiguitanensis differs from C. gibbifer with its orbicular (vs. suborbicular-obtuse) shape, absence (vs. presence) of the ventral inflation on the throat, absence (vs. presence) of a boss on the limb of the labellum, and the number of nerves seen on the margin of the labellum, 27-nerved (vs. 12-nerved). It can also be easily distinguished from other Corybas in the Philippines by the distinct coloration of the labellum, which is predominantly black, except for a bright magenta patch and margin on the limb., Published as part of Tandang, Danilo N., Docot, Rudolph Valentino A., Galindon, John Michael, Jr, Tomas Reyes, Tadiosa, Edwin R., Tandang, Sue Dixie A., Moran, Cecilia B. & Bustamante, Rene Alfred Anton, 2023, Corybas hamiguitanensis (Orchidaceae), a new species from a UNESCO world heritage site in the Philippines, pp. 80-88 in Phytotaxa 598 (1) on pages 82-85, DOI: 10.11646/phytotaxa.598.1.6, http://zenodo.org/record/7958825, {"references":["Schlechter, F. R. R. (1923) Corybas Salisb. oder Corysanthes R. Br.? Repertorium specierum novarum regni vegetabilis. Centralblatt fu ¨ r Sammlung und Veroffentlichung von Einzeldiagnosen neuer Pflanzen Beihefte 19: 18 - 24. https: // doi. org / 10.1002 / fedr. 19230190104"]}
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- 2023
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5. A revision of Alpinia sect. Myriocrater (Zingiberaceae) of the Philippines with a description of a new species
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Rudolph Valentino A. Docot, Cecilia I. Banag-Moran, Sarah Grace S. Zamudio, and Danilo N. Tandang
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Plant Science ,Ecology, Evolution, Behavior and Systematics - Published
- 2022
6. Acranthera philippinensis Merr. 1913
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Ordas, Jorge Anton D., Zamudio, Sarah Grace S., and Docot, Rudolph Valentino A.
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Tracheophyta ,Magnoliopsida ,Acranthera philippinensis ,Rubiaceae ,Biodiversity ,Plantae ,Taxonomy ,Gentianales ,Acranthera - Abstract
Acranthera philippinensis Merr. (1913:32), Figure 1 Type: — PHILIPPINES. ZAMBOANGA, Sax River, 27 November 1911, E . D. Merrill 8309 (lectotype L0058764!, designated here; isolectotypes: US 00137842!, P03801517!). Description: —Unbranched pubescent ground herb, 40–70 cm tall, with tissues that turn brown to black when dry. Stem angular, densely pilose with brown to graying trichomes. Leaves opposite; petioles 1.4–7.0 cm long, strigose to strigulose, often with lenticels; leaf-blades thinly chartaceous to membranous, ovate to oblong-lanceolate, 8.5–25.0 × 3.3–10.0 cm, adaxially sparsely tomentose to villous, densely tomentose along the midrib and lateral veins, abaxially sparsely puberulent, densely tomentose along the midrib and lateral veins, base cuneate or obtuse, apex acute to slightly acuminate, margins ciliolate; lateral nerves 7–10 on each side, reticulated, slightly depressed adaxially, prominent abaxially; stipules persistent, broadly ovate to triangular, with a prominent but decurrent keel, 16–25 × 5–7 mm, densely villose, apex acute, margins ciliolate. Inflorescences of one or two terminal cymes comprising 15–20 flowers, 2.0– 3.5 cm in diameter, primary and secondary peduncles 9–11 mm long, strigose to strigulose; bracts in two whorls pinkish to light red, elliptic, apex acute, pubescent, outer bracts 15–25 × 5–10 mm, sometimes with a small protrusion less than 1 mm at the base, inner bracts 11–18 × 3–10 mm; bracteoles linear, 2 mm long, pubescent; pedicel dark red, 3–5 mm long, pubescent. Flowers 4 to 6-merous; calyx ovary portion densely strigose, cylindrical, dark red, 9–11 mm long; calyx lobes 4 to 6, puberulent, elliptic to oblong, pinkish 8–10 × 3–4 mm, margins ciliolate; corolla white, hypocrateriform, 9–11 × 2–3 mm, densely pubescent outside, inside glabrous; tube 6–8 × 2–3 mm, densely pubescent; lobes broadly ovate to acute, 3.0–3.3 × 2.0–3.0 mm, apex acute to obtuse, tip hispid. Stamens 4 to 6, inserted at the base of the corolla tube, filaments 0.5 mm; anthers linear, 6 mm long, appearing connate surrounding the pistil; pistil 6 mm long, style 5 mm long, stigma globose, 1 mm long. Fruit berry-like, pink to dark red, narrowly oblong, villous to pubescent, 20 × 3–4 mm, crowned with persistent calyx lobes. Distribution and Habitat: — Acranthera philippinensis is endemic to Mindanao, Philippines, to the provinces of Zamboanga City and Zamboanga del Sur (Figure 2). It occurs along small streams or in humid forested areas in wet humus soils, at elevations of 700– 900 m. a.s.l. In 1919, a set collection of A. philippinensis (M. Ramos & G.E. Edaño 36647) was collected in Mount Tubuan, District of Zamboanga. According to Google Maps, however, Mount Tubuan is a low-elevation mountain located in the province of Maguindanao which is outside the political borders of the District of Zamboanga in the early 1900s. Hence, we have concluded that Mount Tubuan is already an extinct name of a mountain located somewhere in the Zamboanga region and therefore, the exact location of (M. Ramos & G.E. Edaño 36647) is at this point, impossible to be determined. Phenology: — Acranthera philippinensis flowers in October–November. Fruits are expected to be observed in January–February. Provisional Conservation Status: —Based on the IUCN red list categories and criteria (IUCN Standards and Petitions Subcommittee 2022), Acranthera philippinensis is categorized as Endangered (EN B2ab(iii), D): B2: area of occupancy (AOO) is estimated to be less than 500 km 2 (AOO is c. 32 km 2), a: known from two locations. Within Mount Timolan, Zamboanga del Sur, seven mature individuals were observed. Unfortunately, there are no other collections aside from the type material found along Sas River, Zamboanga City (type locality) and neighboring localities among the herbaria visited. One of the threats identified would be the continuous conversion of forests into agricultural land within the two localities’ vicinities, which would likely contribute to the decline of A. philippinensis. The assessment will be updated when more localities with habitats suitable for A. philippinensis have been explored, including those in neighboring provinces. Notes: — Merrill (1913) described this species based on several sheets and marked it as a new generic record in the Philippines. As the sole representative of the genus in the country, it is easily recognizable from other genera by its unique floral features, and it is distinct from other Acranthera found in other countries by its numerously flowered cymes and pinkish, accrescent calyx lobes. Merrill also noted that A. philippinensis has cymes that are 7–10 cm in diameter with numerous 4 to 5-merous flowers. Our material showed that one cyme is only 2.0– 3.5 cm in diameter, and thus may have measured several cymes altogether. Our material also showed that some flowers are 6-merous as well. Merrill indicated E. D. Merrill 8309 as the type series represented by several sheets in his 1913 protologue. As part of the Bureau of Science collection, a sheet would have been deposited in PNH. It was confirmed, however, that this was destroyed during World War II. Hence, a lectotype must be chosen from the surviving duplicates following ICN Article 9.3 (Turland et al. 2018). Since the sheet at L has the best-preserved vegetative and reproductive parts, this study designated it as the lectotype and the remaining sheets will be considered as isolectotypes. Additional specimens examined: — PHILIPPINES. ZAMBOANGA CITY: Sax River, 16 February 1905, R. S . Williams 2357 (US): DISTRICT OF ZAMBOANGA: Mount Tubuan, October 1919; fl; M . Ramos & G. E. Edaño 36647 (L, US, P); ZAMBOANGA DEL SUR: TIgbaO, Barangay LImas, MOUnt TImOlan, 7°48′00.1″N, 123°14′45.0″E, 827 m, 30 NOvember 2018, fl, R. V. A . Docot et al. ZMT18-025 (FEUH incl. spirit, USTH)., Published as part of Ordas, Jorge Anton D., Zamudio, Sarah Grace S. & Docot, Rudolph Valentino A., 2023, A rare Philippine plant found again after almost a century: the rediscovery and lectotypification of Acranthera philippinensis (Rubiaceae), pp. 136-140 in Phytotaxa 578 (1) on pages 137-139, DOI: 10.11646/phytotaxa.578.1.8, http://zenodo.org/record/7517812, {"references":["IUCN Standards and Petitions Subcommittee. (2022) Guidelines for using the IUCN Red List Categories and Criteria. Version 15.1 Prepared by the Standards and Petitions Committee. Available from: https: // nc. iucnredlist. org / redlist / content / attachment _ files / RedListGuidelines. pdf (accessed 9 November 2022).","Merrill, E. (1913) Studies on Philippine Rubiaceae, I. Philippine Journal of Science 8: 1 - 32.","Turland, N. J., Wiersema, J. H., Barrie, F. R., Greuter, W., Hawksworth, D. L., Herendeen, P. S., Knapp, S., Kusber, W-H., Li, D-Z., Marhold, K., May, T. W., McNeill, J., Monro, A. M., Prado, J., Price, M. J. & Smith, G. F. (2018) International Code of Nomenclature for algae, fungi, and plants (Shenzhen Code) adopted by the Nineteenth International Botanical Congress Shenzhen, China, July 2017. Regnum Vegetabile 159. Koeltz Botanical Books, Glashutten. https: // doi. org / 10.12705 / Code. 2018"]}
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- 2023
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7. A rare Philippine plant found again after almost a century: the rediscovery and lectotypification of Acranthera philippinensis (Rubiaceae)
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Ordas, Jorge Anton D., Zamudio, Sarah Grace S., and Docot, Rudolph Valentino A.
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Tracheophyta ,Magnoliopsida ,Rubiaceae ,Biodiversity ,Plantae ,Taxonomy ,Gentianales - Abstract
Ordas, Jorge Anton D., Zamudio, Sarah Grace S., Docot, Rudolph Valentino A. (2023): A rare Philippine plant found again after almost a century: the rediscovery and lectotypification of Acranthera philippinensis (Rubiaceae). Phytotaxa 578 (1): 136-140, DOI: 10.11646/phytotaxa.578.1.8, URL: http://dx.doi.org/10.11646/phytotaxa.578.1.8
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- 2023
8. Orchipedum shareeanniae (Orchidaceae), a new species from Samar, Philippines
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Jorge Anton D. Ordas, Danilo N. Tandang, Sarah Grace S. Zamudio, Rudolph Valentino A. Docot, and Cecilia B. Moran
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Plant Science ,Ecology, Evolution, Behavior and Systematics - Published
- 2022
9. Sulettaria , a new ginger genus in the flora of the Philippines
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Kean Roe F. Mazo, Rudolph Valentino A. Docot, and Axel Dalberg Poulsen
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Plant Science ,Ecology, Evolution, Behavior and Systematics - Published
- 2022
10. Using molecular data to test the generic placement of a new and unusual ginger species from the Philippines
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Rudolph Valentino A. Docot, Kean Roe F. Mazo, Noe P. Mendez, and Axel Dalberg Poulsen
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Plant Science ,Ecology, Evolution, Behavior and Systematics - Published
- 2022
11. Risk Minimization Activities and Measures of Effectiveness: A New Approach
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Rudolph Valentino
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Pharmacotherapy ,Risk analysis (engineering) ,business.industry ,Public Health, Environmental and Occupational Health ,Medicine ,Pharmacology (medical) ,Pharmacy ,Minification ,business ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) - Published
- 2018
12. Safety Analysis of Four Randomized Controlled Studies of Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma or Mantle Cell Lymphoma
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Graeme Fraser, Angela Howes, Paul M. Barr, Carol Moreno, Steven Coutre, Jessica Vermeulen, Emily Liu, Susan O'Brien, Thorsten Graef, Marie Sarah Dilhuydy, Lori Styles, Paula Cramer, Alessandra Tedeschi, Stephen Chang, Danelle F. James, Peter Hillmen, Kalpesh Patel, Rudolph Valentino, Georg Hess, and Jan A. Burger
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Chronic lymphocytic leukemia ,Lymphoma, Mantle-Cell ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Piperidines ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Adverse effect ,Aged ,Aged, 80 and over ,Sirolimus ,business.industry ,Adenine ,Standard treatment ,Antibodies, Monoclonal ,Atrial fibrillation ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Discontinuation ,Survival Rate ,Diarrhea ,Pyrimidines ,chemistry ,030220 oncology & carcinogenesis ,Ibrutinib ,Pyrazoles ,Chlorambucil ,Female ,Mantle cell lymphoma ,Patient Safety ,medicine.symptom ,Rituximab ,business ,Follow-Up Studies ,030215 immunology - Abstract
Background Multiple studies have demonstrated the efficacy and safety of ibrutinib for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). This first-in-class inhibitor of Bruton's tyrosine kinase has become a standard treatment for patients with CLL and MCL. Patients and Methods We conducted an integrated safety analysis to characterize the frequency, severity, natural history, and outcomes of adverse events (AEs) with ibrutinib versus comparators. Data were pooled from 4 completed randomized controlled studies that had included 756 ibrutinib-treated and 749 comparator-treated patients with CLL/SLL or relapsed/refractory MCL. Safety analyses included reporting of AEs using crude and exposure-adjusted incidence rates. Results The median treatment duration was 13.3 months (maximum, 28.2 months) for ibrutinib and 5.8 months (maximum, 27.3 months) for comparators. When adjusted for exposure, diarrhea, atrial fibrillation, and hypertension were the only common grade ≥ 3 AEs more often reported with ibrutinib than with the comparators. Dose reductions (7% vs. 14%) and discontinuation (12% vs. 16%) because of AEs occurred less often with ibrutinib, and deaths due to AEs occurred at similar rates (6% vs. 7%). When adjusted for exposure, the corresponding data were all lower with ibrutinib than with the comparators (0.06 vs. 0.22, 0.11 vs. 0.22, and 0.06 vs. 0.09 patient-exposure-years, respectively). The prevalence of common grade 3/4 AEs with ibrutinib generally decreased over time, with the exception of hypertension. Conclusion These results from an integrated analysis support a favorable benefit/risk profile of ibrutinib in patients with CLL/SLL and MCL.
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- 2018
13. Integrated and Long-Term Safety Analysis of Ibrutinib in Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
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Steven Coutre, Paul M. Barr, Jacqueline C. Barrientos, Joi Ninomoto, Rudolph Valentino, Susan O'Brien, Michael O'Dwyer, Samuel Suzuki, Jan A. Burger, Danelle F. James, Paolo Ghia, Richard R. Furman, Peter Hillmen, Carol Moreno, Anna Schuh, John C. Byrd, Tadeusz Robak, Stephen Devereux, and Thomas J. Kipps
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030213 general clinical medicine ,medicine.medical_specialty ,business.industry ,Extension study ,Bulky Disease ,Treatment duration ,Immunology ,Cell Biology ,Hematology ,Biochemistry ,Lymphocytic lymphoma ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,030220 oncology & carcinogenesis ,Internal medicine ,Ibrutinib ,medicine ,In patient ,Long term safety ,business ,Prolonged treatment - Abstract
Background: Ibrutinib (ibr), a first-in-class, oral once-daily inhibitor of Bruton's tyrosine kinase, is indicated by the US FDA for the treatment of pts with CLL/SLL and allows for treatment without chemotherapy. Unlike chemotherapy that is given for a finite number of cycles, ibr is continued until progressive disease (PD) or unacceptable toxicity, leading to extended ibr treatment duration in many patients. The objective was to examine safety and tolerability of ibr therapy in pts with treatment-naïve (TN) or relapsed/refractory (R/R) CLL/SLL using an integrated safety analysis approach, and conduct an analysis of long-term safety. Methods: In study PCYC-1112 (RESONATE), pts with R/R CLL/SLL received ibr 420 mg orally once-daily vs. ofatumumab (Byrd, N Engl J Med 2015). In study PCYC-1115 (RESONATE-2), pts age ≥65 years with TN CLL/SLL received ibr 420 mg orally once-daily vs. chlorambucil (Burger, N Engl J Med 2015). Progressing pts could enroll in the extension study PCYC-1116 for next line therapy (including ibr). Data from ibr-treated pts from the above randomized controlled studies were pooled for an integrated safety analysis. In study PCYC-1102, pts with TN or R/R CLL/SLL received ibr 420 mg or 840 mg orally once-daily (Byrd, N Engl J Med 2013; O'Brien, Lancet Oncol 2014). Pts could continue receiving ibr in the long-term extension study PCYC-1103 where adverse event (AE) collection was limited to grade ≥3 AEs, major hemorrhage, or AEs leading to ibr dose modification. Only data from pts treated with ibr 420 mg daily were examined herein. Results: The integrated analysis included 330 pts; 51% Rai III/IV, 54% bulky disease ≥5 cm, 28% del11q, and 37% CrCl 1 year, 193 (58%) for >2-3 years, and 53 (16%) for >3 years. Concomitant medications included 50% antiplatelet agents, 28% anticoagulants, 3% granulocyte growth factors, and 2% IVIG. The most common AEs were diarrhea (53%) and fatigue (36%). Other AEs experienced by ≥25% of pts were upper respiratory tract infection (30%), nausea (29%), pyrexia (28%), and anemia (27%). Grade ≥3 AEs reported in ≥5% of pts were neutropenia (18%), pneumonia (12%), anemia (7%), and hypertension (HT, 6%). AEs of interest were primarily grade 1/2 (Table). AEs of any grade that led to dose reductions and discontinuation were reported in 13% and 19% of pts, respectively. AEs leading to discontinuation in >1 pt were pneumonia (n=4), anemia (n=3), atrial fibrillation (AFib, n=3), diarrhea (n=2), subdural hematoma (n=2), and thrombocytopenia (n=2). 29 pts died (9%), the most common causes of death were PD (n=8), and pneumonia/lung infection (n=7). In PCYC-1102/1103, 94 pts were treated with ibr for a median of 47.9 mo (max 67.4 mo). The most frequent grade ≥3 AEs were similar to those observed in PCYC-1112 or PCYC-1115/1116, and at times, reflect higher cumulative rates given the median 19 additional months of treatment and follow-up; grade ≥3 AEs reported in ≥5% of pts were hypertension (30%), pneumonia (17%), neutropenia (15%) atrial fibrillation (11%), diarrhea (9%), cellulitis (7%), thrombocytopenia (7%), hyperglycemia (7%), fatigue (6%), decrease in lymphocyte count (6%), and sepsis (5%). Most frequent malignancies included basal cell carcinoma (n=4), squamous cell carcinoma (n=4), and myelodysplastic syndromes (n=2). In 7 of 15 pts, the malignancy AE was diagnosed during the first year, while others occurred over time throughout the ongoing follow-up of >4 years. Overall survival for R/R pts was 74% at 36 mo in PCYC-1112, and 62% at 60 mo in PCYC-1102/1103. Survival of TN pts was 95% at 24 mo in PCYC-1115/1116, and 91% at 60 mo in PCYC-1102/1103 (Kaplan-Meier estimates). Conclusions: In these analyses, which included up to 5 years of follow up in TN and R/R CLL treated with single agent ibr, AEs were primarily grade 1/2 and were manageable with prolonged treatment. Disclosures Coutre: Janssen: Consultancy; Pharmacylics, LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Research Funding. Hillmen:Pharmacyclics: Research Funding; Janssen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Abbvie: Research Funding. Barr:Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy. Devereux:Roche: Consultancy, Other: Travel, Accommodations, Expenses ; Gilead: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Janssen: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; GSK: Consultancy. Robak:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Kipps:Celgene: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria. Schuh:Roche: Consultancy, Honoraria; GSK: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria. Furman:Genentech: Consultancy; Janssen: Consultancy; Abbvie: Consultancy, Honoraria; Gilead Sciences: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau. Burger:Janssen: Consultancy, Other: Travel, Accommodations, Expenses; Roche: Other: Travel, Accommodations, Expenses; Gilead: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Research Funding; Portola: Consultancy. O'Dwyer:Roche: Other: Travel, accommodations, expenses; Novartis: Consultancy; Glycomimetics: Consultancy; Amgen: Consultancy, Other: Travel, Accommodations, Expenses ; BMS: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Equity Ownership, Honoraria, Research Funding; NUI Galway: Patents & Royalties. Ghia:Abbvie: Consultancy, Honoraria; Adaptive: Consultancy; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria, Research Funding. Valentino:Gilead: Equity Ownership; Pharmacyclics, LLC, an AbbVie Company: Employment, Other: Travel, accommodations, and expenses; AbbVie: Equity Ownership; Corvus: Equity Ownership; Johnson and Johnson: Equity Ownership, Other: Travel, accommodations, and expenses. Suzuki:AbbVie: Equity Ownership; Pharmacyclics, LLC, an AbbVie Company: Employment, Other: Leadership; Travel, Accommodations, Expenses. Ninomoto:AbbVie: Equity Ownership; Pharmacyclics, LLC, an AbbVie Company: Employment; Amgen: Equity Ownership. James:AbbVie: Equity Ownership; Pharmacyclics, LLC, an AbbVie Company: Employment. O'Brien:Janssen: Consultancy, Honoraria; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding.
- Published
- 2016
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