Blogs of Professor(Dr.) Pranab Kumar Bhattacharyya MD(cal.Univ) Pathology; : Title= The Hypothetical Planet -9 does at all exis...

Blogs of Professor(Dr.) Pranab Kumar Bhattacharyya MD(cal.Univ) Pathology; : Title= The Hypothetical Planet -9 does at all exis...:   Title= The Hypothetical Planet -9 does at all exist into our solar system or may not exist at all By authors   Rupak Bhattach...

Title= The Hypothetical Planet -9 does at all exist into our solar system?

By authors

Rupak Bhattacharya1, Pranab Kumar Bhattacharya2, Upasana Bhattacharya3,Ritwik Bhattacharya4, Rupsa Bhattacharya5, AyisheeMukherjee5, Dalia Mukherjee5, Hindole Banerjee5  Debasis Mukherjee ⁵

¹     BSc (Calcutta University.), MSc(Jadavpur University.) of Residence -7/51 Purbapalli, Po-Sodepur, Dist- 24 Parganas (north), Kolkata-110, West Bengal, India, Theoretical Physicist.  No Institutional attachment present

²     MBBS (Calcutta Univ.) Honours , M.D (Calcutta Univ.), FIC Path (India), Professor of Pathology, Calcutta School of Tropical Medicine, Kolkata-700073, West Bengal, India; ----now as  Professor of Pathology at Murshidabad District Medical College, Berhampore,  station Road , Murshidabad, West Bengal, India, Member of Board of Studies(UG/PG) of West Bengal University of Health Sciences, DD 36 Salt lake,  sector -1, Kolkata-64

³      Student and only daughter of Prof. Pranab kumar Bhattacharya

⁴      B.com (Calcutta Univ.), of Residence 7/51 Purbapalli, PO-Sodepur, Dist 24 Parganas (north), Kolkata-110, West Bengal, India

⁵Residence 7/51 Purbapalli, Po-Sodepur, Dist 24 Parganas (north), Kolkata-110, West Bengal, India

E-mial  address

profpkb@yahoo.co.in (P. K. Bhattacharya)   mobile +91 9231510435

 corresponding author  :   Professor Dr. Pranab Kumar Bhattacharya²  --:  Professor of Pathology, Calcutta School of Tropical Medicine, Kolkata-700073, West Bengal, India; ----now as  Professor of Pathology at Murshidabad District Medical College, Berhampore,  station Road , Murshidabad, West Bengal, India, and  Member of Board of Studies(UG/PG) of West Bengal University of Health Sciences, DD 36 Salt lake,  sector -1, Kolkata-64

 profpkb@yahoo.co.in )   mobile +91 9231510435

 

Introduction and History of Planet X or planet-9

 Konstanin Batygin and Michael E brown of California Institute of Technology USA in their recent published paper in  “ The Astronomical journal”  titled paper  as “ Evidence of  a distant  giant planet in solar system “ vol 151 No 2 , January 20 ^[1] ;suggested a  hypothetical planet [ rather a  theoretical model]  and it is orbiting in our solar system in a highly  elliptical orbit ,a gas giant  icy planet as Kupier belt objects (KBO)  and compared this hypothetical planet to “Neptune” only as to mass which  were previously thought  as clustering of  6 (six) out of 13  known icy objects (KBO)  those orbited beyond Neptune , in our solar system in the outer Kuiper / inner  Oort  clouds  and astronomers named it as “ Planet -9” is that Planet X? . Approximately  8000 years ago,  the Sumnerian  tablets interpreted  by Stichen  and others  also clearly  stated  the existence  of such planets  and called it as “Planet X” . “Pallas  asteroid”  was considered once to be ninth planet of our solar system in chronological discovery order from 1802 until its reclassification  as a planetismal in  1850s.  In 1866 ,  a  French mathematician,  Urbain – Le- Verrier  predicted also  the existence of a giant gas planet orbiting between the sun and mercury  from the irregularities  detected  in the orbit of Uranus.  He called it   “Vulcan” and it turned out  not to exist at all. About 100 years or so there was another planet candidates to the planetary club. A planet called “ Vulcan” orbiting between mercury and sun . It was U – Le- Verrier, who called this hypothetical planet  as “ Vulcan” after the Greek God  Fire. If this planet existed it would be so hot as it would be very close to sun. In 1859 an armature  astronomer named “ Edmond  Modeste Uscar Bault” observed a dark spot  travelling across the sun. Having previously observed the transit of mercury many years earlier he guessed that it must  be  a transit  of another unknown planet . He contacted Le Verrier   who perhaps  in his desire to see his hypothesis to come to truth, accepted Uscar Bault’s hypothesis and Le Verrier’s discovery of Vulcan . Many more transit were observed then in the next centuries. None of them confirmed the existence of “Vulcan”. Albert Einstein’s paper “ Explanation of perihilon motion of mercury from general relativity theory” Predicted  murcury’s perhilion precession without needing and extra planet.      Astronomers at Berlin observatory, found the new planet “Neptune” where it was supported to be. Remaining hiccups in “Uranus” orbit  led scientists to think  that there might be  one  or more  giant gas planets  and in 1960, Percival Lowell speculated and  began to search for that what was called by him  as “ Planet X” in our solar system . Claims of Planet -9’s existence recalled us a period in 19^th century  when astronomers predicted  and then discovered Neptune  by studying tiny perturbations in the orbit  of Uranus. The Gravity of some unseen body must be tugging on Uranus they said and they were very right. So Pluto was also considered to be the ninth planet from its discovery in 1930  until its reclassification  as a “Dwarf planet” in 2000. Neptune  was the ninth closest planet  from the sun  from 1979- 1999 when Pluto was considered  the 8^th closest planet  from the sun

In 2005, Michael E Brown spotted an object that officially became known as “Eris” (He however preferred the name – Xena). Eris was about as big as Pluto which was still then a planet.  The existence of Eris raised troubling questions such as what a planet is?  Question raised  if Eris was a planet then why not other small icy spheres that orbits  our sun are also planet?  In the end, International Astronomical Union (IAU) categorized “Eris” and “Pluto” as dwarf planets. So instead of ten planets our solar system has now 8 planets.  What we now call planet are objects that can dominate the neighborhood planets by gravitation . Pluto is slave to gravitational influence of Neptune. So it was no more considered as planet.

Beginning of Story of “Planet -9” within  thousands icy objects of  Kuiper Belt (KBO)

 The story of “Planet-9” began in 2014, when a pair of astronomers scientists Scott Sheppard and Chad Trujillo reported findings KBO called 2012 VP₁₁₃ in journal “Nature” that discussed the potential  existence of a giant planet affecting the orbit of their dwarf planet word . It stretched  out orbit  never came closer  to sun  of 80 AU ^[2].   2012 VP₁₁₃ joined  the dwarf planet  when Sedna as only second  known  object with  a very distance  orbit.  Scott Sheppard of the Carnegie Institution of Science and Chad Trujillo of Hawaii's Gemini Observatory, who suggested the unusual orbits of certain objects such as sednoids might be influenced by a massive unknown planet at the edge of the Solar System^[2]. They said that the orbits of these objects suggest another big object – a planet bigger then  planet earth which might exist at around 250 AU. Sedna, VP 113 and several other KBOs all showed a peculiar property. Their closest approach to the sun lay in the plane of the solar system and they all moved from south to north when crossing the plane. 

 Trans Neptune Objects(TNOs) and Jehoshaphat not detected by Telescope

 It was previously known clustering of six (6) of 13 known objects that orbited beyond “Neptune” in our solar system as KBO largely unaffected by the presence of “Neptune”. It was Chad Trujillo & Scott Sheppard (2014) to note that a set of Kuiper Belt objects (KBOs) in the distant solar system exhibits unexplained clustering in orbital elements ^[2]. They are called Trans Neptunian Objects (TNOs), whose orbit  lie mostly beyond Kuiper belt.  Clustering  of six (6) extreme Trans-Neptunian objects  were in a stable configurations of orbits mostly outside the Kuiper belt (they are Sedna populations , 2012 VP₁₁₃, 2007 TG₄₂₂, 2004 VN₁₁₂, 2013 RF₉₈, 2010 GB₁₇₄ RF 98, 2010 GB ₁₇₄), and the perpendicular tilt (orbit with a right angle, compared to the other objects) of other objects such as 2008 KV₄₂, 2012 DR₃₀. K  Balygin and Michael Brown  said in their published paper in the journal  “ The Astronomical Journal” of US  that there are 0.007% chance or above one in 15,000 that clustered of above six(6) icy world  can be a coincidence , instead they said that a planet with mass of 10 earth  and size of 3 earth has shaped the six KBOs  into their elliptical orbits tilted out  of plane of solar system and they named the planet as  “Jehoshaphat’ . Batygin  and Michael Brown  have not however  detected the planet directly  by any telescopes  in the northern hemisphere sky by 27 feet wide  Saburu telescope in Hawaii nor the planet was found  by Hubble or voyager  telescope I [ Voyager 1 is 134 AU distantat presently ] & II[ Voyager II is 110AU presently] pictures but  two astronomers  and theoretical physicist inferred it’s existence  based  on  way  it gravitationally sculpts the strange  orbits of small icy objects beyond Pluto  in Kuiper belt  by the  computer simulation study.

About the Giant Planet- Planet-9 How much distant it is?  

 This giant planet has a mass of 10 times mass  of the earth m' = 10 m_⊕. Estimated mass of the planet- 9 is 6x 10²⁵ with a radius of 13000Km to 26000 Km [i.e. 8,100 to 16,000 miles] compared to 6371 KM for planet the earth and based on motion of Kuiper belt objects, it  has an orbital period of 10,000 -20,000 years with sun’s major axis  roughly 700 AU [about 20 times the distance of Neptune from the sun] and it is in an highly elliptical orbit around sun  tilted out of the plane of solar system. Its closest approach to our sun is seven times farther then Neptune or 200 AU [ 30 billion Km] and its inclination estimated  to be 30+-20 degree.  An astronomical unit (AU) is the distance between  earth and sun i.e. 150 million kilometer (Km) and  the planet- 9 so should be as far  as 600 AU --- 1200 AU, well beyond  the Kuiper belt , the region of small icy world  that begins at Neptune edge -about 30AU . Should we worry of this planet if at all exist for alien life? We must not.

  It is much harder to spot a planet far out of the solar system and so it must be a hypothetical planet’s claim and we are still in dark if at all it exists so long it is not viewed and spotted. A planet produce no light of it’s own  and the planet that is  far from the sun  is going to reflect very little  light , since it receives  very little  solar radiations  to begin with . Rather distant galaxies are much easier to spot being brilliant sources of radiations. The authors Batygin and Brown tested their hypothesis by carrying out both analytical calculations and numerical N-body simulations designed to determine if the gravitational influence of a distant, planetary-mass companion can explain the behavior we observe from the large-orbit KBOs.  So it isn’t possible to exactly determine the properties of this possible hypothetical planet, since multiple combinations of its mass, eccentricity, and semi major axis can create the same observational results we think so.

 How and when the planet -9 was formed?

 The hypothetical planet of Batygin and Brown called it as “Planet Jehoshaphat ” orbits  our sun every 15000 to 20,000 years, ten times massive and three times larger than our planet the earth. This planet is 200-300 times as far away  from the sun  and enter orbit of sun probably takes 20,000 years only once. This planet was probably formed during the solar system’s infancy, more than 4.5 billion years ago and was knocked out planet forming core region near our sun. Slowed down gas and dusts, this hypothetical planet settled into distant elliptical orbit where it still lurks composed of rocks and Ice. The planet might have made its way out the edge of our solar system when it was thrown out by the gravity of Jupiter or Saturn. As such distance of the planet could be impossible to spot even with strongest telescope as little light is sent back from that far away that it may never make it back for us to see.

Four planet core or Five ?

 Where planet- 9 did came from and how did it end up in the outer solar system? 4.5 billion Years ago, our sun was one of many stars incubating in an inter stellar nursery – a nebulae of dust and gas . Eventually all but one of the stars wondered off and when the first planets Jupiter , Saturn,  Uranus,  Neptune were formed- a residue of nebulae remained. At first these four planets were just cores. So the early solar system began with four planetary cores that went on to grab all gas around them forming the four planets like Jupiter, Saturn, Uranus and Neptune. Over time collisions and ejections, shaped them and moved them out their parental location is the present theory. But of course there is no reason that there could not have been five cores rather than four cores. Planet-9 may represent the fifth core if it got close to Jupiter or Saturn it would had been ejected into distant eccentric orbits of the solar system what Batigin and Brown told^[2] .

Is there Possibility of Alien life in Planet-9?

 The surface of the planet -9 must be too much cooler and icy and let us assume it composed of rocks and ice with a small envelop of gas similar to Uranus and Neptune. Let us assume that Planet -9 has a solid surface and their lies water (?) to support life. How much justification will be there to colonize for human being or if intelligent civilization already exist there how much possibility will they communicate with us as alien ?  How much times then will you take to go to planet -9 if at all such a planet with solid surface and water exist in KBO? The Space craft  “ New Horizon”  that  crossed few months before Pluto & Neptune  and with that if it flows  from its current position  it will require infinite  amount  of time and fuel. New Horizon space craft will never have that much fuel to mess around on an extra trip. In order to get to planet-9 it will locally make a huge course of adjustment and probably does not have enough fuel to reach there. The second thing is that how long the New Horizon space craft will take to reach in planet-9?  New Horizon does not travel at constant speed in space time and there space time is not flat also.  If we consider still  with an estimated maximum speed for a space craft  16 Km/ second  and if this space craft is targeted  towards  planet-9  during its closest approach to our sun  in its orbital path  that would have to travel  a distance of 200 AU i.e. 2.99 x10¹³ miles. Now let us assume that by future technology the New space craft   reached planet-9, we yet do not know whether the planet -9 has at all any atmosphere like  ours earth to support life . If the planet-9 has atmosphere and we know that atmosphere of a planet have large impact on its surface temperature. If we assume  our sun is a  black body ( all radiations  is from surface temperature)  then one can assume  the power energy radiated equally  from black body  in every directions , then the intensity  of light  will decrease  one over distance squared. As a planet receives radiation from the sun the surface of the planet is warmed up. When this happens the planets also becomes black body radiator. The Equilibrium temperature of the planet is the point at which estimate and receives radiation equally.  But the planet-9 surface temperature will not be enough to have water to support intelligent life or civilization.

Let me assume that planet -9 has a solid surface can we walk on it if we can ever land there is another question.  This has to do with surface gravitational field. On the surface of the earth the gravitational field is 9.8 Newton per kg. We all know what it feels on the surface of the earth.  The surface gravitational field for a planet depends on two things

1)       The mass of the planet  2)  The radius of the planet

 

The more massive the planet is greater is the gravitational field and larger the radius of the planet lesser the gravitational field and so

g=GM/R² when G= 6.67 x10-¹¹Nm²/kg² and using high and low estimate for the radius of the Planet-9 the gravitational is between 5.9 and 23.7 N/kg. So it may be possible that the gravitational field may be like earth and we can walk if it is near 9.8N/kg. But the planet will be too much cooler and icy world

Now the questions rose to these authors like us

1)       Why we are assuming it as a planet? What we call planets are objects that that can have gravitationally dominate their neighborhoods planets. Planet-9 dominates more the solar system than any known planets.                                                                                                                                           Some of the oldest objects in our galaxy are likely to be remnants of brown dwarf sun that are no longer producing any heat and are now made of some kinds of metals like Fe or Nickel core. There are many objects in the Kuiper belts that have orbits around sun but are sort of  bunched to outside solar system .In 1922  Astronomers  showed the first evidence that Kuiper belt  has  a population of thousands icy objects orbiting the sun at a distance of 30-50 AU. It may be a large object  like brown dwarf planet or a large asteroid

2)      Is the hypothetical planet can be Nibrue or Sedna? Nibrue and Sedna have similar eccentric objects and they are 10 billion Km distance from the earth and orbit our sun in a period of 26000 years. Sedna was discovered in 2003 by M. Brown himself.  Brown and his colleagues Chad Trugillo and David Rabinowin had spotted Sedna an icy object with an eccentric orbit outside  the Kuiper Belt . It comes no closer to sun than 900 AU. Sedna is typically referred  to as extreme  in Oort cloud  another reservoir  of icy scraps which is thought to occupy the utmost edge of our solar system. Sedna  has elliptical orbit  of 11,400 years and between 76 AU & 937 AU( which is 2.5 to 31 times distant from sun to Neptune). Its discovery led suggestion that it was an inner Oort cloud objects deflected by a passing star  or by a large unseen objects.

3)       Does the planet-9 is the main source of long period’s comets? Does this affects  the developing understanding of galactic tides on the Oort cloud roughly 30 million years? The Kuiper belt  is home to many objects formed in the Uranus and  Neptune  region  4.5 billion years ago. Rosetta’s comet  67P comes from here. Even more comets  populate the spherical but yet unseen. Oort cloud  is another belts of rocks and ice far beyond the Kuiper belt where most comets spend most of their time. Oort cloud is  10,000 AU distant from sun.

We have several near masses within our stars in galaxy. The gravitational effects of these stars warped the Kuiper belt objects off the plane ecliptic. Some planets being 20 times the distance of Neptune away from the sun would have had devastating gravitational effects from these rouge stars. Would a planet get enough radiation to spin away from the sun? Some paper theorize that Jupiter  or may be Saturn  forced close to sun and moved further  out  a later date due to  effects they left on the inner planets orbit. What if it was this planet of spinning into the sun became almost all of its forwarded speed was removed by one those passing star. So there is no reason that this Planet-9 still exist in our solar system

4] Observational aspects of the distant Kuiper Belt   have not yet addressed specially in 150–250 AU regions and it is just a speculation. 

5] Every few years some one astronomers announces discovery of Planet X or some large objects that galloped and for centuries finally missed.

6] The planet -9 may not exist  at all. These is a conjectural body  and until we see it for real it will be always questionable whether it exist at all. Icy giants are prevalent through out our galaxy

 Words 3361

 References

·         1] Konstanin Batygin and Michael E brown Evidence of  a distant  giant planet in Solar system “ The Astronomical journal  vol 151 No 2 , January 20

·         2] Trujillo C. A. and Sheppard S. S. 2014 Nature 507 471-474
 

This article had been Published in the  US  journal "Lost Origins.com " as a comment no 1 to the article" "Existence of Planet X" on 25 th January 2016 under strict  copy Right of authors as per IPR based Copy Right Rules as stated  above
Lost Origin
This organization would be nothing without the brave pioneers who paved the proverbial path before us. Graham Hancock, Andrew Collins, Philip Coppens, David Childress, Jason Martell, David Wilcock, and many more have had the courage to make the claim that “what is accepted by modern academia and archeology needs to be reexamined.” This act of fortitude sparked the fire at Lost Origins. Our goal is to provide you with the most recent and relevant theories, concepts, and evidence that challenge modern schools of thought.

    

Submitted the article

As Letter To the Editor  in Journal   The Astronomical journal USA   and in external peer review process

 please click on the link http://iopscience.iop.org/article/10.3847/0004-6256/151/2/22/meta  for the full article  on planet-9 as titled

 Decision of " The Astronomical Journal"  of American Society of Astronomy  USA 

Subject:	AJ-13060: Your manuscript submitted to The Astronomical Journal

Dear Prof. Bhattacharya, Regarding your paper to be considered for publication in The Astronomical Journal, Manuscript number: AJ-13060 Title: The Hypothetical Planet -9 does at all exist into our solar system or may not exist at all Authors: Bhattacharya et al. The Astronomical Journal only publishes papers based on the gathering, reporting and analysis of observational data. We do not publish letters, even if they are intended as comments on previously published papers. Consequently, we are unable to consider your paper or similar manuscripts for publication. Regards, Ethan T. Vishniac AAS Editor-in-Chief Johns Hopkins University

 Decision letter of the Journal NEWASTRONOMY of Elsevier Science on dated 11th Feb 2016

Re: The Hypothetical Planet -9 does at all exist into our solar system or may not exist at all
    by
 Professor Dr  Pranab Kumar Bhattacharya, MD(Calcutta Univ) FIC path(india0; Rupak  Bhattacharya, Bsc( Calcutta Univ) Msc(Jadavpur University); Upasana  Bhattacharya; Ritwick Bhattacharya, B.Com(calcutta University); Rupsa  Bhattacharya; , Ayishee  Mukherjee; , Dalia  Mukherjee, BA(Honors)( Calcutta University); Hindole  Banerjee, BA ; Debasis  Mukherjee, Bsc(calcutta University)   Submitted to New Astronomy by manuscript no NEWAST-D-16-00024 as letter to the Editor

Dear  Prof .Dr. Bhattacharya,

We have read your paper and hypothesis  submitted to "New Astronomy" as letter to the Editor  and after External Peer Review we determined that the content of your work is not however within the scope of this journal. We hope you will be able to find a more appropriate journal for your hypothesis on existence of Planet -9 in our solar system .
Thank you for giving us the opportunity to consider your work.
Yours sincerely,
Managing Editor
New Astronomy Journal
homepage: www.elsevier.com/locate/newast

EVIDENCE FOR A DISTANT GIANT PLANET IN THE SOLAR SYSTEM

Konstantin Batygin¹ and Michael E. Brown¹

Published 2016 January 20 • © 2016. The American Astronomical Society. All rights reserved. • The Astronomical Journal, Volume 151, Number 2

 

 

Copy Right  Declaration  Please note  it very carefully that, The Copy Right of this article belongs only to Professor Pranab kumarBhattacharya MD(cal) FIC path(Ind)  the 2^nd author here, and other authors in chronological orders  as per copy right rules of IPR1996 applicable in India-2006  under sections 306/3D/107/1012 a, b / RDF and Protect Intellectual Property Right(PIP)  ACT of USA-2012  SPARC authors amended Copy Right rules-2006  of US and copy right works  and applicable  when & if accepted for any other blogs,  or as a reference, or as a publication  or as any Research  or as  reference materials  or published as paper or article in open access journals or as a commissioned article or writing any book or thesis   and then  also this article will be under RDF Copy Right rules of IPR of Prof P. K Bhattacharya. No person/persons from any states of  country India or any citizen of India or of Indian origin are for ever authorized by Professor Pranab kumar Bhattacharya to use  any  scientifically meaningful syllables/words  /sentences from this published blog article  published in the Blogs of Prof Pranab kumar Bhattacharya MD(cal.univ) FIC path(ind.) in Blog spot.com  without his / or future copy right  owner ‘s  by written permission  & copy Right clearance, even for any one’s personal  use or knowledge or for his/her fair use even/ or teaching or  any kind of dissemination  in public  or class  room  or through books of  any information from this published  article ( Will be considered  then as Plagiarism by prof Pranab kumar Bhattacharya here the 2nd author ) , [except such all permission is always remain granted to other authors ,their first degree blood relatives in what ever manner they want to use this article  for ever from the date of publication in Prof Pranab Kumars Bhattacharya MD(cal) FIC path(ind)  Blog at blog spot.com   or for digital preservation of  the article in National Level Science Library(NSDL) US or of other countries.- by declaration-
Please be careful enough for your own safety  
SD/ Professor Pranab kumar Bhattacharya WBMES

 

 

 

Ibrutinib can be used in CLL who have developed P17 deletion also

Now@NEJM

Ibrutinib as Initial Therapy for CLL

Posted by Carla Rothaus • December 18th, 2015

New England Journal of Medicine

Now@NEJM

New England Journal of MedicineIbrutinib as Initial Therapy for CLL

Posted by Carla Rothaus • December 18th, 2015

Clinical Pearls

• What are some of the limitations of current first-line therapies for CLL?

All current standards for first-line CLL therapy are based on cytotoxic chemotherapy, including alkylating agents, purine analogues, or combinations thereof, except for patients with chromosome 17p13.1 deletion, for whom ibrutinib is a primary consideration for first-line therapy according to consensus guidelines. In addition to their myelosuppressive effects, these cytotoxic chemotherapy approaches may be associated with expansion of subclones with high-risk genetic abnormalities (e.g., TP53 or NOTCH1 mutation) and an increased risk of secondary cancers, including treatment-related myelodysplasia and acute myeloid leukemia.

• Is progression-free survival prolonged with the use of ibrutinib as compared to chlorambucil in patients 65 years of age or older with previously untreated CLL?

In the study by Burger et al., ibrutinib resulted in significantly longer progression-free survival than that with chlorambucil (median, not reached vs. 18.9 months) as assessed by the independent review committee, with a relative risk of progression or death that was 84% lower than that with chlorambucil (hazard ratio, 0.16; 95% confidence interval [CI], 0.09 to 0.28; P<0.001). The rate of progression-free survival at 18 months was 90% in the ibrutinib group versus 52% in the chlorambucil group. The results of the analysis of progression-free survival were consistent in the higher-risk subgroups, including patients with advanced-stage cancer, higher ECOG performance-status score, presence of chromosome 11q22.3 deletion, and nonmutated IGHV status.

Figure 1. Progression-free Survival with Ibrutinib versus Chlorambucil.

Morning Report Questions

Q: How do overall survival and response rates compare among patients 65 years of age or older with previously untreated CLL who receive ibrutinib as compared to chlorambucil?

A: In the study by Burger et al., ibrutinib significantly prolonged overall survival (median, not reached in either group). The overall survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death with ibrutinib that was 84% lower than that with chlorambucil (hazard ratio, 0.16; 95% CI, 0.05 to 0.56; P=0.001). The response rate as assessed by the independent review committee was significantly higher in the ibrutinib group than in the chlorambucil group (86% vs. 35%). Furthermore, ibrutinib-treated patients had a restoration of bone marrow function, with a significantly higher rate of sustained improvement in hematologic variables.

Figure 2. Overall Survival and Response Rates with Ibrutinib versus Chlorambucil.

Figure 3. Hematologic Variables over Time in the Safety Population.

Q: What adverse events were associated with ibrutinib in the Burger study?

A: The safety of ibrutinib in this older population of patients with CLL who often had clinically significant coexisting conditions was consistent with that in previous reports. Exposure to treatment and adverse-event follow-up was nearly 2.5 times as long with ibrutinib as with chlorambucil. In the ibrutinib group, diarrhea was the most frequent adverse event (in 42% of the patients, including grade 3 diarrhea in 4%). Other adverse events that occurred in 20% of the patients in the ibrutinib group were fatigue, nausea, and cough. Similar to findings in previous reports about ibrutinib, major hemorrhage was observed in 4% of the patients, with no fatal events, and atrial fibrillation occurred in 6%, with the majority of the events (in six of eight patients) being grade 2 events that were observed over the period of 1.5 years while the patients were taking ibrutinib. Hypertension was reported more frequently with ibrutinib than with chlorambucil, with no events leading to dose modification or having a severity of grade 4 or 5. The rates of fatigue, nausea, vomiting, and myelosuppression were higher with chlorambucil than with ibrutinib. Early discontinuation of treatment owing to adverse events was more than twice as frequent with chlorambucil as with ibrutinib

Tags: chlorambucil, Chronic lymphocytic leukemia (CLL), cytotoxic chemotherapy, ibrutinib
Posted in Physicians-In-Training | Permalink | 1 Comment

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1. Professor Dr Pranab kumar Bhattacharya says:

   December 31, 2015 at 2:40 am

   Ibrutinib can be used in CLL who have developed P17 deletion also
   
2. ibrutinib is a Brutons’s tyrosine kinase inhibitor was used first in Mantle cell lymphoma but there were relapses too . Mantle cell lymphoma is a rare type B cell malignancy in NHL that results expression of Cyclin D1 and there occurs dysregulation of cell cycle control and has poor prognosis Burton tyrosine kinase is a vital component of B cell signaling. Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. Over the past 3 years, ibrutinib (PCI-32765) has emerged as a breakthrough in targeted therapy for patients with certain types of B cell malignancies. Early stage clinical trials found ibrutinib to be particularly active in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) ibrutinib is not myelosuppressive, and responses are not affected by disease features that predict failure to respond to or short remission durations after chemo-immunotherapy, such as del17p. In CLL, ibrutinib characteristically causes an early redistribution of tissue-resident CLL cells into the blood, with rapid resolution of enlarged lymph nodes, along with a surge in lymphocytosis. Later, after weeks to months of continuous ibrutinib therapy, the growth- and survival-inhibitory activities of ibrutinib result in the normalization of lymphocyte counts and remissions in a majority of patients.
   Ibrutinib are also in trial of Pancreatic adenocarcinoma.
   Most adverse events are grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation may be continued to 12.5 mg/kg per day without reaching MTD
   In India indication of Use of Ibrutinib are Chronic lymphocytic leukemia (CLL) who have received at least one prior treatment ; Chronic lymphocytic leukemia (CLL) with 17p deletion ; Mantle cell lymphoma (MCL) who have received at least one prior treatment The drug is available in Mumbai, Kolkata, Hyderabad, Chennai, Ahmedabad, Delhi, Bangalore and Puneon basis of Valid prescription of Oncologist

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