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ASH 2018: Dr. Mato on Testing Before Treatment in chronic lymphocytic leukemia (CLL)

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We have to know our enemy before we decide how to best target therapy. That is why testing before treatment is critical and why it is tragic when it is not being done.

At ASH 2018, I interviewed Dr. Anthony Mato, a CLL expert at Memorial Sloane Kettering in New York City, about his research on what was happening in terms of testing  in the real world of CLL patientsDr. Mato and I discussed his research with two different registries including the new research findings that he presented at ASH 2018.

Connect CLL looked at 199 medical US centers between 2010-2014 before the era of novel agents. The new drug approvals really ushered in the need to do predictive testing in CLL as we had clear evidence that novel treatments were dramatically better for certain patients with specific predictive markers.

The second registry was InformCLL that gathered data from 150 centers (96% community, 4% academic) between 2015-18 when the value of predictive testing to support therapy choices was well established.

One would think that in the more recent years, appropriate testing would be more common, but in fact, the numbers of patients getting the lab test that they need has fallen.

The three tests that need to be done before treatment are:

  1. FISH (fluorescence in situ hybridization) that looks inside the CLL cells for chromosome abnormalities. Especially important is the finding of a deletion of the short arm of the 17th chromosome or del(17p) that strongly predicts poor response to chemotherapy.
  2. Testing for mutations in TP53. TP53 is the gene on the short arm of the 17th chromosome that helps chemo to work and suppress cancer growth. If it’s missing as in del(17p) or mutated as discovered by genetic testing, generally chemotherapy will not work.
  3. IGVH mutation status is the third test and helps predict one’s chances of having a durable response to chemo. Unmutated IGVH (U-CLL) patients generally have a shorter time to disease progression.

The first two tests need to be done before the first and any subsequent treatments as they can change over time, usually for the worse. IGVH mutation status is nearly always stable over time.


  • Testing
    • Connect CLL registry showed < 2/3 of patients (pts) had FISH testing and 6% had IGVH testing performed prior to the first chronic lymphocytic leukemia (CLL)-directed treatment
    • Only 40% had repeat FISH testing prior to a subsequent therapy.
    • InformCLL 2015-18 examined the data on 840 pts (459 previously untreated; 381 relapsed or refractory (R/R).
    • Among all pts (N=840), 262 (31%) had FISH testing, 89 (11%) had testing performed for TP53 mutation, and 94 (11%) had testing for IGHV mutational status.
    • In the 381 R/R pts, the numbers were even worse. Only 98 (26%) had testing for FISH, 35 (9%) for TP53, and 39 (10%) for IGHV.
  • Treatment
    • Not only was the testing not being done, when it was done, the results were often not being used to best inform therapy.
    • More than 1/3 of the 70 pts with del(17p) received chemotherapy or chemo-immunotherapy (CT/CIT) which is most unlikely to work.
    • Of the 14 previously untreated pts with mutated TP53, (36%) received CT/CIT that is generally not indicated in with mutated
    • Among 69 pts with unmutated IGVH that predicts for worse outcomes with CT/CIT, 32 of the pts (46%) received CT/CIT.
    • In 35 previously untreated pts with unmutated IGVH, CT/CIT was more common (n=20; 57%) than ibrutinib (n=13; 37%).
    • Of the pts tested who had abnormalities such as del(17p), TP53mutation, or U-CLL, approximately one-third still received CT/CIT.


We have our work cut out for us.

Not only are too few patients getting the testing they need, the trend is moving in the wrong direction. Moreover, when patients relapse and they especially need to be retested, it is happening even less.

Finally, in the greatest tragedy that these results highlight, even when the appropriate testing is done, the results aren’t influencing therapy choices and patients are getting treatments that are not likely going to help them.

This is heartbreaking.

This has to stop.

That is why we launched Test Before Treat.

That is what our motto Smart Patient Get Smart Care™ is all about.

Here is my interview with Dr. Anthony Mato:

Here is the link to the ASH 2018 abstract that gives all the details.

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