Min­i­mal Resid­ual Dis­ease: A Prog­nos­tic Fac­tor Mov­ing the Nee­dle in Pa­tient Care

As tech­nol­o­gy ad­vances, in­no­v­a­tive di­ag­nos­tic tools that may help guide ther­a­peu­tic de­ci­sion-mak­ing are be­com­ing avail­able to more and more health­care pro­fes­sion­als (HCPs).

In the past, blood can­cers like acute lym­phoblas­tic leukemia (ALL) were pri­mar­i­ly eval­u­at­ed un­der a mi­cro­scope to de­tect re­main­ing can­cer­ous cells dur­ing and af­ter treat­ment. Now, there are more pre­cise tools to iden­ti­fy minute amounts of can­cer, known as mea­sur­able or min­i­mal resid­ual dis­ease (MRD), present at con­cen­tra­tions that less sen­si­tive tests, such as mi­croscopy, could not de­tect.1

Tests for MRD have shown to bet­ter as­sess drug re­sponse and re­lapse risk than stan­dard tech­niques, the re­sults of which will equip HCPs with more ac­cu­rate in­for­ma­tion about which pa­tients may re­quire fur­ther in­ter­ven­tion and which can be spared ad­di­tion­al ther­a­py.1

“Over the last 20 years we have made sig­nif­i­cant ad­vance­ments not on­ly in the sci­ence of MRD de­tec­tion, but in its po­ten­tial im­pact as it re­lates to treat­ment of pa­tients liv­ing with cer­tain blood can­cers,” said David M. Reese, M.D., se­nior vice pres­i­dent, Trans­la­tion­al Sci­ences and On­col­o­gy, Am­gen.

“The tech­nol­o­gy has ad­vanced to the point where we def­i­nite­ly need to re­de­fine what our goals of ther­a­py are, and for every pa­tient with a blood can­cer we should be striv­ing to achieve an MRD neg­a­tive re­mis­sion,” said Aaron Lo­gan, M.D., PhD. hema­tol­o­gist.

MRD is usu­al­ly eval­u­at­ed in one of two ways. The first, called flow cy­tom­e­try, us­es cell-sur­face pro­tein mark­ers to dif­fer­en­ti­ate be­tween cells that are nor­mal and those that are can­cer­ous.2MRD can al­so be test­ed through DNA-based meth­ods that can iden­ti­fy ge­net­ic al­ter­ations and over-ex­pressed genes re­spon­si­ble for caus­ing can­cer.2

Com­pared to con­ven­tion­al test­ing meth­ods that de­tect can­cer cells in the bone mar­row or blood with a sen­si­tiv­i­ty of about 1 in 20, these MRD test­ing meth­ods have im­proved de­tec­tion to sen­si­tiv­i­ties of 1 in 10,000 cells or bet­ter.2,3

Re­gard­less of the method used to mea­sure MRD, a neg­a­tive sta­tus has been shown to cor­re­late with im­proved clin­i­cal out­comes.4Ac­cord­ing to Dr. Lo­gan, MRD sta­tus is “an ex­treme­ly im­por­tant prog­nos­tic fac­tor for pre­dict­ing whether a pa­tient is like­ly to re­lapse af­ter achiev­ing re­mis­sion.”

Be­cause MRD is a quan­tifi­ca­tion of dis­ease bur­den, it can al­so be lever­aged at sev­er­al points in time, not just af­ter the achieve­ment of re­mis­sion.1,4

“There’s a grow­ing in­ter­est in us­ing MRD not on­ly for risk strat­i­fy­ing pa­tients and to pre­dict their out­comes, but al­so to iden­ti­fy strate­gies for in­ter­ven­ing up­on resid­ual dis­ease,” said Dr. Lo­gan.

When used dur­ing treat­ment, MRD lev­els can in­di­cate a pa­tient’s re­sponse to ther­a­py, as Dr. Lo­gan ex­plains.1De­spite the im­pact MRD can play on risk strat­i­fi­ca­tion for pa­tients, Dr. Lo­gan notes not all labs are able to de­tect MRD at lev­els sen­si­tive enough to un­der­stand the true im­pact.

How­ev­er, he adds, “aware­ness of the im­por­tance of MRD is in­creas­ing. I do think more and more providers who see ALL pa­tients are go­ing to be find­ing ways to con­duct MRD as­sess­ments on their pa­tients.”

Be­yond ALL, MRD test­ing has been used across a va­ri­ety of hema­to­log­ic ma­lig­nan­cies, in­clud­ing oth­er types of leukemia, cer­tain lym­phomas, and mul­ti­ple myelo­ma.5Clin­i­cal re­search con­tin­ues to ex­plore the sig­nif­i­cance of MRD in these can­cers.

“We still have a ton of work to do to,” Dr. Lo­gan ex­plains, “to in­ves­ti­gate in all of these blood can­cers what is the thresh­old at which we should change ther­a­py, what are the most ef­fec­tive ther­a­pies and then once you achieve an MRD-neg­a­tive re­mis­sion, what do you do then to main­tain that re­mis­sion?”

Ul­ti­mate­ly, Dr. Lo­gan be­lieves that the field is head­ing in a di­rec­tion that will lead to bet­ter de­ci­sion mak­ing.

Out­side of the lab, the path ap­pears to be mov­ing quick­ly. Ac­cord­ing to a 2017 analy­sis by the U.S. Food and Drug Ad­min­is­tra­tion, near­ly 40 per­cent of new drug and bi­o­log­ics li­cense ap­pli­ca­tions sub­mit­ted to the Di­vi­sion of Hema­tol­ogy Prod­ucts be­tween 2014 and 2016 in­clud­ed MRD da­ta.6

“At Am­gen, we have been able to take what we are see­ing in the lab af­ter ex­am­in­ing resid­ual can­cer cells and ap­ply these learn­ings to our clin­i­cal de­vel­op­ment pro­grams,” said Reese. “As test­ing for MRD con­tin­ues to ad­vance and be­comes more com­mer­cial­ly avail­able, there is every ex­pec­ta­tion that treat­ment ap­proach­es will evolve to help bet­ter care for these pa­tients.”


For more in­for­ma­tion on MRD and oth­er ad­vance­ments in on­col­o­gy, please vis­it www.AmgenOn­col­o­gy.com.

Ref­er­ences:

  1. Paeit­ta E. Bone Mar­row Trans­plant. 2002;29:459-465.
  2. Brügge­mann M, et al. Blood. 2012;120:4470-4481.
  3. Gök­buget N, et al. Blood. 2012;120:1868-1876.
  4. Berry D, et al. JA­MA On­col. 2017; 3:e170580.
  5. van der Velden VH, et al. Leukemia. 2003;17:1013-1034.
  6. Gorm­ley N, et al. J Clin On­col.2017;35:(sup­pl; ab­str 2541)

USA-103-80026

Nick Leschly via Getty

UP­DAT­ED: Blue­bird shares sink as an­a­lysts puz­zle out $1.8M stick­er shock and an un­ex­pect­ed de­lay

Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.

Ted Love. HAVERFORD COLLEGE

Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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Bain’s biotech team has cre­at­ed a $1B-plus fund — with an eye to more Big Phar­ma spin­outs

One of the biggest investors to burst onto the biotech scene in recent years has re-upped with more than a billion dollars flowing into its second fund. And this next wave of bets will likely include more of the Big Pharma spinouts that highlighted their first 3 years in action.

Adam Koppel and Jeff Schwartz got the new life sciences fund at Bain Capital into gear in the spring of 2016, as they were putting together a $720 million fund with $600 million flowing in from external investors and the rest drawn from the Bain side of the equation. This time the external investors chipped in $900 million, with Bain coming in for roughly $180 million more.

They’re not done with Fund I, with plans to add a couple more deals to the 15 they’ve already posted. And once again, they’re estimating another 15 to 20 investments over a 3- to 5-year time horizon for Fund II.

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Neil Woodford, Woodford Investment Management via YouTube

Un­der siege, in­vest­ment man­ag­er Wood­ford faces an­oth­er in­vest­ment shock

Em­bat­tled UK fund man­ag­er Neil Wood­ford — who has con­tro­ver­sial­ly blocked in­vestors from pulling out from his flag­ship fund to stem the blood­let­ting, af­ter a slew of dis­ap­point­ed in­vestors fled fol­low­ing a se­ries of sour bets — is now pay­ing the price for his ac­tions via an in­vestor ex­o­dus on an­oth­er fund.

Har­g­reaves Lans­down, which has in the past sold and pro­mot­ed the Wood­ford funds via its re­tail in­vest­ment plat­form, has re­port­ed­ly with­drawn £45 mil­lion — its en­tire po­si­tion — from the in­vest­ment man­ag­er’s In­come Fo­cus Fund.

Search­ing for the next block­buster to fol­low Darza­lex, J&J finds a $150M an­ti-CD38 drug from part­ner Gen­mab

Now that J&J and Genmab have thrust Darzalex onto the regulatory orbit for first-line use in multiple myeloma, the partners are lining up a deal for a next-gen follow-on to the leading CD38 drug.


Janssen — J&J’s biotech unit — has its eyes on HexaBody-CD38, a preclinical compound generated on Genmab’s tech platform designed to make drugs more potent via hexamerization.


Genmab is footing the bill on studies in multiple myeloma and diffuse large B-cell lymphoma; once it completes clinical proof of concept, Janssen has the option to license the drug for a $150 million exercise fee. There’s also $125 million worth of milestones in play.

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Ab­b­Vie touts new da­ta for Hu­mi­ra suc­ces­sor; Gilead inks dis­cov­ery deal

→ Ab­b­Vie is tout­ing new pos­i­tive da­ta com­par­ing their ag­ing block­buster Hu­mi­ra with their hoped-for block­buster upadac­i­tinib. Over 48 weeks a larg­er pro­por­tion of pa­tients tak­ing the ex­per­i­men­tal drug ex­pe­ri­enced clin­i­cal re­mis­sion than in the con­trol arm with Hu­mi­ra. Their drug brought in $20 bil­lion last year, top­ping the scales in the num­ber 1 slot.

→ Gilead has turned to Van­cou­ver-based Ab­Cellera for its lat­est dis­cov­ery deal. Ab­Cellera will use its know-how in “sin­gle-cell screen­ing of nat­ur­al im­mune sources” to find an­ti­body can­di­dates for Gilead to pur­sue in the in­fec­tious dis­ease field. The deal in­cludes an up­front and mile­stones.

Turns out, Rudy Tanzi did­n't see much of a sto­ry about a hid­den link be­tween En­brel and Alzheimer's ei­ther

The Wash­ing­ton Post man­aged to whip up the quick­est in­dus­try con­sen­sus I’ve ever seen that one of its re­porters was pur­vey­ing overblown non­sense with a sto­ry that Pfiz­er was sit­ting on da­ta sug­gest­ing that En­brel could be an ef­fec­tive treat­ment for Alzheimer’s. 

In cov­er­ing that bit of an­ti-Big Phar­ma fan­ta­sy — there are lots of rea­sons to go af­ter phar­ma, but this piece was lu­di­crous — I not­ed com­ments in the sto­ry from some promi­nent peo­ple in the field crit­i­ciz­ing Pfiz­er for not pub­lish­ing the da­ta. I sin­gled out Rudy Tanzi at Har­vard and then ap­plied some added crit­i­cism for the things he’s done to hype — in my opin­ion — high­ly ques­tion­able as­sump­tions. You can see it in the link.