Frequently Asked Questions: IS RT-Q-PCR Testing

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1 Questins 1. What is chrnic myelid leukemia (CML)? 2. Hw des smene knw if they have CML? 3. Hw is smene diagnsed with CML? Frequently Asked Questins: IS RT-Q-PCR Testing Answers CML is a cancer f the bld and bne marrw in which the bdy prduces t many white bld cells. Chrnic stands fr relatively slwer-grwing cancer that may take years t prgress and myelid refers t the type f white bld cell being verprduced. Almst all patients with CML have a chrmsmal abnrmality knwn as the Philadelphia chrmsme. This chrmsme prduces a prtein called BCR-ABL which signals the bne marrw t keep making abnrmal white bld cells. Over the last 15 years, CML treatments have been develped t inhibit r blck the BCR-ABL prtein, which helps t slw the reprductin f abnrmal white bld cells. Signs and symptms f CML include: fatigue, shrtness f breath, pale skin, night sweats, unexplained weight lss and abdminal pain r sense f fullness. Signs and symptms f CML tend t develp gradually, s patients ften learn they have CML after a rutine physical exam r a bld test. T diagnse smene with CML, a dctr takes samples f bld and bne marrw. These samples are then sent t a lab t lk fr the presence f leukemia cells. 4. Hw is CML treated? Current CML treatments, knwn as tyrsine kinase inihibitrs (TKIs), inhibit r blck the BCR-ABL prtein, which helps t slw the reprductin f abnrmal white bld cells. The level f BCR-ABL in a patient s bld indicates the amunt f disease present in the bdy and hw well the patient is respnding t treatment. A PCR test can detect whether the level f BCR-ABL in a patient s bld is being reduced. 5. What is IS RT-Q-PCR? IS RT-Q-PCR stands fr Internatinal Scale Real-Time 6. What can a patient expect when getting a PCR test? 7. Hw ften shuld a CML patient have a PCR test? Quantitative Plymerase Chain Reactin. The IS is a means fr standardizing and validating a patient s test results; The RT-Q-PCR, als knwn as PCR, is a simple and cnvenient bld test that measures the amunt f leukemia in the bdy. Once diagnsed with CML and n treatment, ne f the mst imprtant tests fr a Ph+ CML patient t get is a PCR test. The PCR test measures BCR-ABL levels, the key cause f Ph+ CML, which can enable a mre precise assessment f respnse t treatment with TKIs. The PCR test is a simple and cnvenient bld test. Peripheral bld is cllected like when yu have yur bld drawn at yur regular checkup. Current guidelines recmmend getting PCR testing every 3 mnths, with a checkpint fr majr mlecular respnse (MMR) after 18 mnths. Once MMR is achieved, a PCR test shuld be cnducted at least every three t six mnths.

2 8. Why is PCR testing imprtant? 9. Why is the IS in IS RT-Q- PCR imprtant? 10. Hw des PCR differ frm ther tests fr CML? 11. Hw des PCR testing differ frm cytgenetic testing? 12. Can yu explain the different levels f mlecular respnse? Are there general guidelines fr when a CML patient shuld achieve these milestnes? A PCR test is the nly test that can detect early signs f resistance, allwing timely interventin befre lss f cytgenetic r hematlgic respnse. Tracking the trend f PCR test results in a patient allws fr timely interventin and can help drive clinical decisins, such as the need t change therapy. A PCR test is the nly test that can cnfirm if MMR and deeper respnses, such as MR4.5, are achieved. Deep mlecular respnses are assciated with a further reductin in risk f prgressin. In rder t standardize the reprting f BCR-ABL levels an internatinal reprting scale (IS) was established, which expresses hw much BCR-ABL is detected in a patient s bld as a percentage. The IS eliminates variatin in the reprting f BCR-ABL levels, and therefre, prvides mre cnsistent and cmparative results amng different labratries. Fr example, if a CML patient needs t change labs, he r she can be reassured that results frm the tw labs are cmparable. PCR is the mst sensitive test currently available in the management f CML. A PCR test can detect a single cell cntaining BCR-ABL amng ne millin nrmal white bld cells, whereas cytgenetic testing can detect ne Ph+ cell ut f 20. The PCR test is less invasive than ther testing methds. Older tests like cytgenetic testing invlve btaining samples f bne marrw frm a patient. These samples are analyzed and cells cntaining the Ph chrmsme are cunted. In cntrast t PCR, which can detect a single cell cntaining BCR-ABL amng ne millin nrmal white bld cells, cytgenetic testing can detect ne Ph+ cell ut f 20. In additin, cytgenetic testing lacks the sensitivity t identify existing leukemia cells belw 1% BCR-ABL, meaning it can t detect the achievement f MMR r MR4.5. A PCR test is the nly test that can cnfirm if MMR and deeper respnses such as MR4.5 are achieved. Achieving and maintaining a deep mlecular respnse, knwn as MR4.5 where BCR-ABL levels f less than r equal t %, is an imprtant milestne fr patients because clinical evidence demnstrates that disease des nt prgress r wrsen in mst patients wh achieve and maintain this milestne. At diagnsis, it has been estimated that patients have a disease burden equivalent t 100% BCR-ABL (apprximately 1 trillin evident Ph+ CML cells) remaining. This is rughly the size f a 10 cm tumr and apprximately equivalent t the size f a man s fist. Experts recmmend certain respnse gals at different time pints: A cmplete hematlgic respnse (CHR) r BCR-ABL levels f 10% at 3 mnths. It has been estimated that at CHR, patients have a disease burden equivalent t 10% BCR-ABL (apprximately 100 billin evident Ph+ cells) remaining. This is rughly the size f a 5 cm tumr and apprximately equivalent t the size f a chicken egg. A cmplete cytgenetic respnse (CCyR) r BCR-ABL levels f 1% at 12 mnths. It has been estimated that at

3 CCyR, patients have a disease burden equivalent t 1% BCR-ABL (apprximately 10 billin evident Ph+ cells) remaining. This is rughly the size f a 2.5 cm tumr and apprximately equivalent t the size f an almnd. A majr mlecular respnse (MMR) r BCR-ABL levels f 0.1% within 18 mnths. It has been estimated that at MMR, patients have a disease burden equivalent t 0.1% BCR-ABL (apprximately 1 billin evident Ph+ cells) remaining. This is rughly the size f a 1 cm tumr and apprximately equivalent t the size f a lima bean. 13. What is MR4.5? It has been estimated that at MR4.5, patients have a disease burden equivalent t % BCR-ABL (apprximately 32 millin evident Ph+ cells) remaining. This is rughly the size f a 0.3 cm tumr and apprximately equivalent t the size f a peppercrn. 14. Is PCR the nly test a CML patient shuld get? 15. Shuld a patient s PCR test results always be exactly the same? 16. Why shuld a CML patient knw his r her PCR test results? MR4.5 is an imprtant milestne fr patients with Ph+ CML as clinical evidence demnstrates that disease des nt prgress r wrsen in patients wh achieve and maintain this milestne. At diagnsis, ther tests are als imprtant. Fr example, a bne marrw test will likely be taken t cnfirm the diagnsis and the phase f the disease a patient s CML is in. A bne marrw test may als be rdered t analyze the genes and identify cells that have the Philadelphia chrmsme. In additin, ther tests may be recmmended fr patients until they achieve CCyR. Once this milestne is achieved, the PCR test is the nly test that will shw existing levels f BCR-ABL and becmes the primary test fr disease mnitring. PCR test results can fluctuate, s it is imprtant fr physicians and patients t track results ver time t determine persnal trends and infrm specific treatment decisins. In general, a patient s PCR test results will usually g dwn significantly ver the first 18 mnths if they are being treated with a TKI. Fr example, adherence/cmpliance t therapy can impact a patient s test results. Often, if a patient s PCR level has gne up, it is a result f missed dses r stpping therapy. There als may be sme variability in the test results if tests are cnducted in different labs. It is imprtant fr a CML patient t knw their PCR test results because it helps track prgress and is an indicatin f hw he r she is respnding t treatment. Hitting a defined BCR-ABL level, as determined between a patient and his r her dctr, shuld be a key gal. Patients shuld knw that achievement f key respnses, such as MMR and MR4.5, indicate reductin f the disease. Mnitring a patient s PCR respnse values ver time allws fr the detectin f earlier trends in BCR-ABL levels and may drive clinical decisins, such as the need t change therapy. If a patient is nt reaching the treatment gals, there may still be ptins; just make sure yu discuss these ptins with yur physician.

4 17. What is the ideal PCR level? A patient s ideal PCR level can change ver time. Fr example, experts recmmend the fllwing: A cmplete hematlgic respnse (CHR) r estimated BCR-ABL levels f 10% at 3 mnths; A cmplete cytgenetic respnse (CCyR) r estimated BCR-ABL levels f 1% at 12 mnths; A majr mlecular respnse (MMR) r estimated BCR-ABL levels f 0.1% within 18 mnths. It is imprtant t wrk with a dctr t establish clear treatment gals, meaning when a patient shuld achieve certain disease milestnes r lwering f BCR-ABL in yur bld. Even if a patient is nt reaching the treatment gals established with their dctr, there may still be ptins; just make sure yu discuss these ptins with yur physician. 18. Hw can rutine mlecular mnitring help patients get t the ultimate gal? 19. Why is it imprtant t achieve mlecular respnse? 20. If a patient s last PCR test scre has gne up, des this mean their treatment is nt wrking? 21. Shuld a CML patient s PCR results always be dne in the same lab? 22. What shuld a CML patient ask their dctr abut PCR testing? The ultimate gal in CML treatment is different fr every patient as it depends n a number f factrs, such as phase f the disease and age, amng thers. But rutine PCR testing is imprtant t evaluate hw a CML patient is respnding t treatment. Tracking the trend f patient mlecular respnses allws fr timely interventin and can help drive clinical decisins. Recent data crrelates early mlecular respnse (a reductin in BCR-ABL transcript levels t 10% at mnths three) with future deeper levels f respnse (MMR and MR4.5), as well as increased prbability f prgressin-free survival and verall survival. Achieving and maintaining a deep mlecular respnse, knwn as MR4.5 r BCR-ABL levels f less than r equal t %, is an imprtant milestne fr patients because clinical evidence demnstrates that disease des nt prgress r wrsen in mst patients wh achieve and maintain this milestne. Sustaining MR4.5 is a prerequisite fr enrllment in mst treatment-free remissin trials which evaluate the next treatment gal in CML therapy. PCR levels fluctuate. Hwever, tracking the trend f a patient s respnses allws fr timely interventin and can help drive clinical decisins. Rising PCR shuld be taken seriusly. A physician will need t evaluate test results n a patient-bypatient basis. Fr nw, patients shuld have their tests analyzed by the same lab s that tracking prgress is easier and cnsistent. While the Internatinal Scale has been established, nt all labs currently use it. There are many effrts underway t ensure cnsistency acrss the glbe, and many labs are adpting IS-standardized PCR testing because it allws fr true assessment f mlecular respnse. Once cnsistency has been established, having an PCR test analyzed in the same lab will likely be less imprtant. It is imprtant fr a CML patient t understand their treatment and testing. Sme questins that may be gd t ask include: What are my treatment gals? In what time frame shuld I expect t achieve these gals? Hw ften shuld I get my mlecular respnse tested?

5 What are my ptins if I am nt meeting my treatment gals in the utlined time frame? Patients shuld ask their dctr fr their PCR percentages because they are easiest t track. It s a gd idea fr patients t keep a jurnal and track their PCR results in a chart t identify trends. It is imprtant fr a CML patient t knw his r her PCR test results because it helps them track their prgress and is an indicatin f hw he r she is respnding t treatment. # # # G-CML